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Sample records for human viral gastroenteritis

  1. Viral Gastroenteritis

    Science.gov (United States)

    ... help relieve the symptoms of viral gastroenteritis in adults: drinking plenty of liquids such as fruit juices, sports ... as the child is hungry giving infants breast milk or full strength ... solutions Older adults and adults with weak immune systems should also ...

  2. Viral Gastroenteritis (Stomach Flu)

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    ... Viral gastroenteritis (stomach flu) Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  3. Etiology and Rapid Diagnosis of Human Viral Gastroenteritis.

    Science.gov (United States)

    1987-05-01

    immunity to rotavirus are complex (1). It seems likely that serum antibody to the virus is associated with protection from illness, and perhaps, local ...three) subgroups of the virus (1). Immune responses are heteroserotypic and heterosubgroup in nature, and various human and animal rotaviruses are...illness typically produces severe diarrhea that commonly lasts for five to eight days and is usually accompanied by fever and vomiting. Rotavirus , which

  4. The Etiology and Pathogenesis of Viral Gastroenteritis.

    Science.gov (United States)

    1983-07-31

    nausea, vomit- ing, low grade fever, abdominal cramps, headache, anorexia, myalgia and malaise. It can be severe, indeed fatal, in the elderly ...infant, debilitated or malnourished patient. Viral gastroenteritis occurs primarily in two epidemiologically distinct clin- ical forms (1). One entity is

  5. Suspicion of viral gastroenteritis does improve compliance with hand hygiene.

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    Scheithauer, S; Oude-Aost, J; Stollbrink-Peschgens, C; Haefner, H; Waitschies, B; Wagner, N; Lemmen, S W

    2011-08-01

    Viral gastroenteritis is common on pediatric wards, increasing the need for adherence with hand hygiene recommendations in order to prevent cross-transmission. Therefore, we investigated hand hygiene reflecting complete work-day activities on pediatric wards and focused on the influence of viral gastroenteritis. There are, so far, no studies representing complete working days on pediatric wards or addressing the influence of viral gastroenteritis. This was a prospective, observational study (144 h in each group) on hand hygiene behavior in the care for children with and without suspected or proven viral gastroenteritis. We documented 40 and 30 hand hygiene opportunities per patient-day for ward-associated healthcare workers for children with and without viral gastroenteritis, respectively (P = 0.316). Healthcare workers' compliance with hand hygiene recommendations was significantly higher in children with viral gastroenteritis compared to those without, i.e., 72 versus 67% (P = 0.033), especially among physicians, being 92 versus 50% (P = 0.032). Compliance tended to be higher after patient contact than before, especially in the children with gastroenteritis (78 vs. 62%; P = 0.083). We conclude that viral gastroenteritis seemed to increase the number of daily opportunities for hand hygiene and did significantly increase compliance. In particular, this effect was seen after patient contact. Further research might address the awareness of undiagnosed transmissible diseases in order to prevent cross-transmissions.

  6. Human Noroviruses and Sporadic Gastroenteritis

    Centers for Disease Control (CDC) Podcasts

    2008-08-05

    In this podcast, Dan Rutz speaks with Dr. Manish Patel, a medical officer with the Division of Viral Diseases at CDC, about an article in August 2008 issue of Emerging Infectious Diseases reporting on nororviruses. Dr. Patel reviewed 235 studies and identified 31 original studies about noroviruses. Norovirus is the leading cause of epidemic gastroenteritis.  Created: 8/5/2008 by Emerging Infectious Diseases.   Date Released: 7/30/2008.

  7. Clinical characteristics of seizures associated with viral gastroenteritis in children.

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    Ueda, Hitoshi; Tajiri, Hitoshi; Kimura, Sadami; Etani, Yuri; Hosoi, Gaku; Maruyama, Tomoko; Noma, Haruyoshi; Kusumoto, Yoshio; Takano, Tomoko; Baba, Yoshiko; Nagai, Toshizaburo

    2015-01-01

    We analyzed the clinical features of seizures during gastroenteritis in children by comparing the norovirus and rotavirus pathogen, and the impact of fever, if present, during the seizure episodes. Retrospective analysis was performed on 293 consecutive pediatric patients admitted with viral gastroenteritis to Osaka General Hospital between November 2007 and May 2009. Eighteen patients developed seizures, 12 of whom were positive for norovirus and six for rotavirus, as revealed by antigen detection. Of these 18 seizure patients, eight presented without fever (the aFS group) and 10 presented with febrile episodes (FS group). Seizure patients in the rotavirus group (83%) were more likely to be febrile than those in the norovirus group (58%). Compared with the aFS group, 90% of patients in the FS group presented seizures at an early stage of gastroenteritis. The frequency of clustered seizures in the FS group was considerably higher than that of febrile seizures in general and was also as high as that of "convulsions with mild gastroenteritis (CwG)". All seizure patients, whether febrile or afebrile, presented with generalized tonic clonic seizures (GTCS), complex partial seizures (CPS), or both. Diazepam (DZP) was less effective and carbamazepine (CBZ) was completely effective for the cessation of seizures in the FS group, similar to the drug response observed in CwG. The causative pathogen (norovirus or rotavirus) affected the frequency of febrile episodes during gastroenteritis, but fever had little effect on the clinical features of seizures. However, seizures occurred earlier during gastroenteritis in the FS group. On the whole, the clinical features of febrile seizures during viral gastroenteritis may closely resemble those of "convulsions with mild gastroenteritis" (CwG) than those of febrile seizures in general with respect to the frequency of clustered seizures and the antiepileptic drug responses and may have a pathogenic mechanism distinct from those of

  8. CARBOHYDRATE MALABSORPTION SYNDROME IN CHILDREN WITH VIRAL GASTROENTERITIS

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    E. R. Meskina

    2015-01-01

    Full Text Available Background: Enteric viruses (mainly rotaviruses are the most common cause of infectious diarrhea in infants. One  of the  pathophysiologic mechanisms in rotaviral gastroenteritis is the  reduction of the  surface  activity of enterocyte disaccharidases  and  osmotic  diarrhea. Aim: To determine the clinical significance of metabolic activity of intestinal microbiota in the formation of the osmotic component of viral diarrhea in children of various ages. Materials and methods: The study involved 139 children aged  from 1 month  to 14 years admitted to the hospital in the first 24 to 72 hours of moderate-degree  viral gastroenteritis.  Rotaviral infection was the most prevalent  (90%. Viral etiology was confirmed  by the  reaction  of indirect hemagglutination and multiplex real-time PCR (in feces. Total carbohydrate content in the feces was measured and fecal microflora was investigated by two methods: bacteriological and gas liquid chromatography with the determination of short-chain fatty acids. Results: The mean carbohydrate content in the feces of children below 1.5 years of age was higher than  that  in older children (p = 0.014. There was an inverse correlation between the concentration of rotaviral antigens  and carbohydrate   contents (r = -0,43, p < 0.05 and the production of acetic and propionic acids (R = -0,35, p < 0.01. The carbohydrate content in acute stage of the disease was linearly associated with time to normalization of the stool (r = +0,47, p < 0.01. Previous acute  respiratory or intestinal  infections within 2 months (odds ratio [OR], 14.10; 95% confidence interval [CI] 3.86–51.53, previous  hospitalizations  (OR = 14.17; 95% CI 2.74–74.32 and  past  history of intestinal dysfunction (OR 5.68; 95% CI 1.67–19.76 were predictive of severe  carbohydrate malabsorption in children below 1.5 years of age. Conclusion: The lack of microbiota functional activity (assessed by production of short

  9. Molecular Epidemiology of Viral Gastroenteritis in Hajj pilgrimage

    KAUST Repository

    Padron Regalado, Eriko

    2014-05-01

    Hajj is the annual gathering of Islam practitioners in Mecca, Saudi Arabia. During the event, gastrointestinal infections are usually experienced and outbreaks have always been a concern; nevertheless, a deep and integrative study of the etiological agents has never been carried out. Here, I describe for the first time the epidemiology of pathogenic enteric viruses during Hajj 2011, 2012 and 2013. The focus of this study was the common enteric viruses Astrovirus, Norovirus, Rotavirus and Adenovirus. An enzyme Immunoassay established their presence in 14.9%, 15.0% and 6.6% of the reported cases of acute diarrhea for 2011, 2012 and 2013, respectively. For the three years of study, Astrovirus accounted for the majority of the viral infections. To our knowledge, this is the first time an epidemiological study depicts Astrovirus as the main viral agent of gastroenteritis in a mass gathering event. Hajj is rich in strains of Astrovirus, Norovirus and Rotavirus. A first screening by RT-PCR resulted in ten different genotypes. Strains HAstV 2, HAstV 1 and HAstV 5 were identified for Astrovirus. GI.6, GII.3, GII.4 and GII.1 were described for Norovirus and G1P[8], G4P[8] and G3P[8] were found for Rotavirus. The majority of the Astrovirus isolates could not be genotyped suggesting the presence of a new variant(s). Cases like this encourage the use of metagenomics (and nextgeneration sequencing) as a state-of-the-art technology in clinical diagnosis. A sample containing Adenovirus particles is being used to standardize a process for detection directly from stool samples and results will be obtained in the near future. The overall findings of the present study support the concept of Hajj as a unique mass gathering event that potentiates the transmission of infectious diseases. The finding of Norovirus GII.4 Sydney, a variant originated from Australia, suggests that Hajj is a receptor of infectious diseases worldwide. This work is part of the Hajj project, a collaborative

  10. Epidemiology of Classic and Novel Human Astrovirus: Gastroenteritis and Beyond

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    Diem-Lan Vu

    2017-02-01

    Full Text Available Since they were identified in 1975, human astroviruses have been considered one of the most important agents of viral acute gastroenteritis in children. However, highly divergent astroviruses infecting humans have been recently discovered and associated with extra-intestinal infections. The report of cases of fatal meningitis and encephalitis, especially in immunocompromised individuals, has broadened their disease spectrum. Although zoonotic transmission among animal and human astroviruses has not been clearly recognized, the genetic similarity between some human and animal viruses makes it likely to occur. This review provides an update on the epidemiology of both classic and novel human astroviruses, and a comprehensive view on confirmed or potential association between astrovirus and human disease.

  11. THE ETIOLOGIC SPECTRUM OF PATHOGENS OF VIRAL GASTROENTERITIS IN CHILDREN FROM BAKU

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    N. N. Aliev

    2016-01-01

    Full Text Available The article presents the results of research on the study of etiology, the logical structure of viral diarrhea in Baku (Azerbaijan in 2015. It was found that more than half (62.6%, gastroenteritis in children of viral etiology, of which the leading role as an etiological factor, have a company — and adenoviruses, among infants astroviruses. But-roviral gastroenteritis and enterovirus takes only insignificant-tive percentage of cases. There were no significant differences in the proportion of virustion of diarrhea depending on the age of the patients was not revealed.

  12. Human bocavirus in children with acute gastroenteritis in Albania.

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    La Rosa, G; Della Libera, S; Iaconelli, M; Donia, D; Cenko, F; Xhelilaj, G; Cozza, P; Divizia, M

    2016-05-01

    Human Bocavirus (HBoV) has been recently identified in association with acute viral gastroenteritis (AGE). The objective of this work was to investigate the prevalence of HBoV in children with AGE in Albania. Stool specimens collected from 142 children were analyzed by amplification of partial NP1 and Vp1/Vp2 genes. HBoV was detected in 13 samples (9.1%), 12 HBoV-1 and one HBoV-2. All HBoV-positive patients were co-infected with rotavirus and/or adenovirus, a finding which might indicate that there is no clear causal association of this agent with diarrhea. Further investigation is needed to assess the pathogenic role of HBoV in childhood diarrhea. © 2015 Wiley Periodicals, Inc.

  13. Novel approach for detection of enteric viruses to enable syndrome surveillance of acute viral gastroenteritis.

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    Svraka, Sanela; van der Veer, Bas; Duizer, Erwin; Dekkers, Jojanneke; Koopmans, Marion; Vennema, Harry

    2009-06-01

    Acute gastroenteritis is one of the most common diseases worldwide, with viruses, particularly noroviruses, being the leading cause in developed countries. In The Netherlands, systematic surveillance of gastroenteritis outbreaks of suspected viral etiology was established by the National Institute for Public Health and the Environment in 1994. Since 2002, the total number of outbreaks reported has been increasing, and with that comes the need for sensitive assays that can be performed quickly. In addition, the diagnostic demand changed so that now the proportion of samples from hospitals is higher and there is a need for patient-based test results. In order to target the diagnosis of acute gastroenteritis, we reviewed our data on outbreaks of gastroenteritis and the prevalence of individual viruses to provide a priority list of viruses for which samples should be evaluated. Random primers were used to replace the separate specific primers for each virus used in the reverse transcription steps. The individual PCR assays were replaced by multiplex PCR assays. We employed a two-step method in which in the first step we screened for the most common causes of viral gastroenteritis, noroviruses of genogroup II and rotaviruses of group A, with equine arteritis virus used as the internal control. Subsequently, in the second step, two parallel PCR assays were developed for the detection of noroviruses of genogroup I and equine arteritis virus in one run and adenoviruses, sapoviruses, and astroviruses in the other run. The specificities of the assays were calculated to be 92.5% for the assay for noroviruses of genogroup I and 100% for the assays for all other viruses, the detection limits were equal for all viruses, and the turnaround time was reduced to 1 day compared to the at least 3 days required for the methods used previously. This approach allows the targeted, rapid, and cost-effective elucidation of the causes of acute gastroenteritis outbreaks.

  14. Viral gastroenteritis associated with genogroup II norovirus among U.S. military personnel in Turkey, 2009.

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    Salwa F Ahmed

    Full Text Available The present study demonstrates that multiple NoV genotypes belonging to genogroup II contributed to an acute gastroenteritis outbreak at a US military facility in Turkey that was associated with significant negative operational impact. Norovirus (NoV is an important pathogen associated with acute gastroenteritis among military populations. We describe the genotypes of NoV outbreak occurred at a United States military facility in Turkey. Stool samples were collected from 37 out of 97 patients presenting to the clinic on base with acute gastroenteritis and evaluated for bacterial and viral pathogens. NoV genogroup II (GII was identified by RT-PCR in 43% (16/37 stool samples. Phylogenetic analysis of a 260 base pair fragment of the NoV capsid gene from ten stool samples indicated the circulation of multiple and rare genotypes of GII NoV during the outbreak. We detected four GII.8 isolates, three GII.15, two GII.9 and a sole GII.10 NoV. Viral sequences could be grouped into four clusters, three of which have not been previously reported in Turkey. The fact that current NoV outbreak was caused by rare genotypes highlights the importance of norovirus strain typing. While NoV genogroup II is recognized as causative agent of outbreak, circulation of current genotypes has been rarely observed in large number of outbreaks.

  15. Prevalence of Norwalk-like virus infections in cases of viral gastroenteritis among children in Osaka City, Japan.

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    Iritani, Nobuhiro; Seto, Yoshiyuki; Kubo, Hideyuki; Murakami, Tsukasa; Haruki, Kosuke; Ayata, Minoru; Ogura, Hisashi

    2003-04-01

    Surveillance of Norwalk-like virus (NLV) infections in cases of pediatric gastroenteritis between April 1996 and March 2000 showed that NLVs were an important causative agent in viral gastroenteritis cases among children between November and January in those years. The predominant type of NLV was closely related to Lordsdale virus in genogroup 2. During the 1999-2000 season, Arg320-like strains, which may be genetic recombinants, suddenly appeared and spread.

  16. Viral gastroenteritis

    Science.gov (United States)

    ... Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016:chap 340. Dupont HL. Acute infectious diarrhea in immunocompetent adults. N Engl J Med . 2014; ...

  17. Seasonal screening for viral gastroenteritis in young children and elderly hospitalized patients: is it worthwhile?

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    Borrows, C L; Turner, P C

    2014-06-01

    Viral gastroenteritis is common, especially in young children. In adults, particularly amongst the elderly, it can lead to outbreaks at a time when demands on clinical services are at their peak. To evaluate seasonal screening of young children and elderly patients with suspected viral gastroenteritis using multiplex polymerase chain reaction (PCR) for enteric viruses within a general hospital setting. Stool samples from 200 children aged five years and under were screened for rotavirus, adenovirus, astrovirus, sapovirus and norovirus using multiplex PCR and a combined rotavirus/adenovirus immunochromatographic test (ICT) during the winter of 2012. Diarrhoeal samples submitted to the laboratory from 195 adults aged 65 years and over attending as inpatients were also evaluated by multiplex PCR. One or more enteric viruses were detected by PCR in 56% of children. Rotavirus was the most prevalent virus, found in 19% of samples. Enteric (diarrhoea-associated) adenovirus was detected in 5% of samples and non-enteric adenovirus was detected in 14% of samples. Astrovirus, norovirus and sapovirus were detected in 18%, 12% and 10% of samples, respectively. The ICT yielded a slightly lower rate for rotavirus and enteric adenovirus, but gave more rapid results. Norovirus, rotavirus and adenovirus were detected in 15%, 2.5% and 1% of elderly adults attending hospital as inpatients, respectively. Rapid screening of young children (for rotavirus, adenovirus and norovirus) and symptomatic, elderly adults (for norovirus) during winter months may help to limit nosocomial spread. Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  18. FilmArray® Gastrointestinal (GI) Panel for Viral Acute Gastroenteritis Detection in Pediatric Patients

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    Kanwar, Neena; Jackson, Jami; Duffy, Susan; Chapin, Kimberle; Cohen, Daniel; Leber, Amy; Daly, Judy a; Pavia, Andrew; Larsen, Chari; Baca, Tanya; Bender, Jeffery; Bard, Jennifer Dien; Festekjian, Ara; Holmberg, Kristen; Bourzac, Kevin; Selvarangan, Rangaraj

    2017-01-01

    Abstract Background Acute viral gastroenteritis is one of the leading causes of diarrheal diseases. The FilmArray GI Panel is a PCR based assay that detects 22 different enteric pathogens including five viruses (Adenovirus F 40/41, Astrovirus, Norovirus GI/GII, Rotavirus A, and Sapovirus (I, II, IV, and V)) in an hour. The epidemiology and management of acute viral gastroenteritis is described. Methods Children with acute gastroenteritis were prospectively enrolled at emergency departments of five geographically different pediatric facilities during 2015–2016. Stool specimens were collected and tested by the FilmArray GI Panel. Results A total of 1157 subjects were enrolled in the study. Stool specimens from 961 subjects were collected. Subjects with viral, bacterial, and parasitic etiology as identified by the FilmArray GI Panel were 429 (44.6%), 392 (40.8%), and 41 (4.3%), respectively. Viral AGE was common in winter months from October through March (274/429; 63.9%); norovirus was the leading viral agent (205/429; 47.8%) and was more commonly detected in winter months (147/205; 71.7%). Other viruses detected include Adenovirus F 40/41, Astrovirus, Rotavirus, and Sapovirus in 94 (9.8%), 49 (5.1%), 28 (2.9%), and 97 (10.1%) specimens, respectively. Co-infections with multiple pathogens was found in 244 (25.4%) of all specimens tested. Only 39/961 subjects received a viral standard of care (SOC) test result. The FilmArray GI panel detected viruses in higher percentage of stool specimens when SOC was not requested 45% (415/922) vs. requested 36% (14/39) [P = 0.32]. Viral infections were the highest among 148 hospitalizations: virus (26.4%), bacteria (22.9%), bacteria and virus (16.9%), and parasite (0.6%) and norovirus was the leading viral etiology associated with hospitalizations (n = 27; 69.2%). AGE due to viral (24.6%) or bacterial (27.6%) causes had similar repeat visits to hospital [P = 0.45]. Conclusion Viruses are leading cause of AGE resulting in ED

  19. Genetic Diversity of Human Adenovirus in Children with Acute Gastroenteritis, Albania, 2013–2015

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    La Rosa, G.; Della Libera, S.; Petricca, S.; Iaconelli, M.; Donia, D.; Saccucci, P.; Cenko, F.; Xhelilaj, G.; Divizia, M.

    2015-01-01

    The objectives of the present study were to assess the occurrence of human adenoviruses (HAdVs) in paediatric patients with gastroenteritis in Albania and to characterize HAdV strains. Faecal specimens from children admitted with acute gastroenteritis to the Paediatric Hospital in Tirana were screened for HAdV, using broad-range primers targeting the hexon gene, in combination with species-specific primers targeting the fiber gene. Phylogenetic analysis was then performed to assess the genetic relationships among the different sequences and between the sequences of the samples and those of the prototype strains. Adenovirus DNA was detected in 33/142 samples (23.2%); 14 belonged to species F (13 HAdV-41 and 1 HAdV-40), 13 to species C (1 HAdV-1, 8 HAdV-2, and 4 HAdV-5), 5 to species B (HAdV-3), and 1 to species A (HAdV-12). Rotavirus coinfection was present in 9/33 (27.2%) positive samples. In the remaining 24 positive samples (12 enteric—F species; 12 nonenteric—A, B, or C species), HAdVs were detected as unique viral pathogens, suggesting that HAdV may be an important cause of diarrhoea in children requiring hospitalization. This is the first study investigating the presence of human adenoviruses (species A–G) as etiologic agents of viral gastroenteritis in children in Albania. PMID:26339589

  20. Genetic Diversity of Human Adenovirus in Children with Acute Gastroenteritis, Albania, 2013-2015.

    Science.gov (United States)

    La Rosa, G; Della Libera, S; Petricca, S; Iaconelli, M; Donia, D; Saccucci, P; Cenko, F; Xhelilaj, G; Divizia, M

    2015-01-01

    The objectives of the present study were to assess the occurrence of human adenoviruses (HAdVs) in paediatric patients with gastroenteritis in Albania and to characterize HAdV strains. Faecal specimens from children admitted with acute gastroenteritis to the Paediatric Hospital in Tirana were screened for HAdV, using broad-range primers targeting the hexon gene, in combination with species-specific primers targeting the fiber gene. Phylogenetic analysis was then performed to assess the genetic relationships among the different sequences and between the sequences of the samples and those of the prototype strains. Adenovirus DNA was detected in 33/142 samples (23.2%); 14 belonged to species F (13 HAdV-41 and 1 HAdV-40), 13 to species C (1 HAdV-1, 8 HAdV-2, and 4 HAdV-5), 5 to species B (HAdV-3), and 1 to species A (HAdV-12). Rotavirus coinfection was present in 9/33 (27.2%) positive samples. In the remaining 24 positive samples (12 enteric--F species; 12 nonenteric--A, B, or C species), HAdVs were detected as unique viral pathogens, suggesting that HAdV may be an important cause of diarrhoea in children requiring hospitalization. This is the first study investigating the presence of human adenoviruses (species A-G) as etiologic agents of viral gastroenteritis in children in Albania.

  1. HUMAN CALICIVIRUS OUTBREAK OF ACUTE GASTROENTERITIS IN AN AGED-CARE FACILITY

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    Iztok Štrumbelj

    2003-05-01

    Full Text Available Background. Human caliciviruses represent a genetically and antigenetically diverse group of single-stranded RNA viruses associated with acute gastroenteritis in humans. In last two years the number of notified gastroenteric cases in Slovenia is increasing. From January till November 2002 already 574 calicivirus cases have been confirmed. Majority of cases were observed in preschool and school children but no cases were described in the aged-care facility.Methods. An outbreak of gastroenteritis in an aged-care facility occured. After onset of the outbreak an epidemiological questionnaire and inspection of local conditions were realized. Stool samples from home residents were analysed to find out bacteriological and/or viral aetiology. Direct electron microscopy and RT-PCR assay was performed to detect caliciviruses. Viral RNA was amplified using specific primers and PCR products were identified in hybridisation test.Results. The outbreak started suddenly on the second floor, where the attack rate was the highest. On the other floors the illness started later and the attack rate was lower. Sixty-one (40,1% residents from 152 became ill and additionally 15 (22,4% employees from 67. The outbreak ended after ten days. Electron microscopy or/and RT-PCR revealed Norovirus members of family Caliciviridae in 9 of 10 stool specimens. As determined by RT-PCR and hybridisation assay viruses corresponded to genogroup II, genetic cluster 1 (closely related to the Hawaii virus and genetic cluster 4 (closely related to the Lordsdale virus.Conclusions. Presented data support a significant role for caliciviruses as causative agents of gastroenteritis in elderly persons in Slovenia.

  2. Molecular epidemiology of norovirus infections in sporadic cases of viral gastroenteritis among children in Northern Italy.

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    Medici, Maria Cristina; Martinelli, Monica; Abelli, Laura Anna; Ruggeri, Franco Maria; Di Bartolo, Ilaria; Arcangeletti, Maria Cristina; Pinardi, Federica; De Conto, Flora; Izzi, Giancarlo; Bernasconi, Sergio; Chezzi, Carlo; Dettori, Giuseppe

    2006-11-01

    Surveillance of norovirus infections in sporadic cases of pediatric gastroenteritis admitted to a main hospital in Northern Italy during a full-year period (2002) showed that noroviruses (10.4%) were the second most common causative viral agent, following rotaviruses (21.1%), and noroviruses (81%) were mostly implicated in mixed infections. The epidemic period of norovirus was September-December, with September and November as months of major prevalence (33.3 and 38.5%, respectively). Six distinct norovirus genotypes were detected (GI.7, GII.1, GII.2, GII.4, GII.7, GII, not assigned named GIIb), and the predominant genotype was GII.4. A "new GII.4 2002 variant" accounted for 82.9% of total strains. Since the severity of norovirus symptoms does not usually require admission to hospital, the burden of norovirus disease in the general children population may be much higher than that suggested by the present hospital-based investigation.

  3. [Acute infectious gastroenteritis in Rio Cuarto: clinic, diagnosis and epidemiology with special reference to viral infections].

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    Soñez, Carlos A; Mugnaini, María T; Godino, Sergio; Soñez, María V; Sánchez, Oscar; Fernández, Sol

    2002-01-01

    The objectives of the present study are to describe the clinics view of acute infectious gastroenteritis (GE) at the community, in primary and secondary attention health centers, with special references to viral aetiology (VIGE); to correlate with drinkable water and excrete treatment; to develop for the first time a fast diagnostic using electron microscopy in Río Cuarto, Córdoba, Argentina, considering the university and community collaboration in the viral diagnostic. It has been during one year, 122 cases of acute GE, over its clinics epidemiology and diagnostic aspects (1999-2000). With conventional laboratory methods, it has been determined the bacteria and micotic aetiology (NOVIGE); the virology diagnostic with electron microscopy; and the use of the statistics for the data analysis. The microbial findings has been: pathogenics bacteria (31.7%), fungus (17%), parasites (1.2%), rotavirus (16.4%), calicivirus (1.6%), adenovirus and coronavirus (1.6%). The clinics findings are presents like digestive and extra-digestive signs, separated in NOVIGE (and no-diagnosticated) and VIGE groups. The seasonal viral and no-viral distributions are present in fig. 5. There are statistics signification: the NOVIGE in summer period (49%) against the VIGE (12.5%) (p 2 years) and season (winter-summer) with the 16% for the first in VIGE (62.5% rotavirus); the absence of health systems at the NOVIGE (70%) and with both (29%); and others epidemiology considerations of the sequence. With came to conclusion that in our city: 1. there are VIGE with signficative participation of rotavirus; 2. its distribution are winter and age group, also considering the other age groups and virosis; 3. the NOVIGE may difference at the clinic sign like vomit, between all the possible sintomatology; 4. the principal cause of diarrhoea and the no seasonal distribution are the NOVIGE; 5. there are not a strong relationship of diarrhoea by shortage environmental health in this study; 6. it's possible

  4. Human adenovirus spread, rainfalls, and the occurrence of gastroenteritis cases in a Brazilian basin.

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    Rodrigues, Manoela Tressoldi; Henzel, Andréia; Staggemeier, Rodrigo; de Quevedo, Daniela Muller; Rigotto, Caroline; Heinzelmann, Larissa; do Nascimento, Carlos Augusto; Spilki, Fernando Rosado

    2015-11-01

    Climate variables may interfere with the environmental persistence and spread of pathogenic microorganisms. This study aimed to investigate the occurrence of human adenovirus (HAdV) and total and thermotolerant coliforms in treated and untreated water and report gastroenteritis cases in seven cities located in the hydrographic basin of the Sinos River (HBSR), Southern Brazil. The data on water quality from samples collected at catchment areas of HBSR from March to December 2011 were compared with precipitation records, virus detection rates and viral loads, and information on enteric diseases among residents of the region. There was a marked increase in precipitation intensity in April, July, and August and a decrease in May and November. The number of HAdV genome copies (gc) in untreated water ranged from 2.1×10(8) gc/L in June to 7.8×10(1) gc/L in December, and in treated water, from 6.3×10(4) gc/L in September to 4.1×10(1) gc/L in November. The most probable number (MPN) of total coliforms ranged from 5×10(1) MPN/100 mL in December to 2.4×10(5) MPN/100 mL in July, and thermotolerant coliforms ranged from 1×10(1) MPN/100 mL in August to 6.9×10(4) MPN/100 mL in July. A total of 79 hospital admissions due to gastroenteritis were registered in the cities studied. The results for coliforms in untreated water demonstrate deficits in sanitation and wastewater treatment. These findings also indicate a possible relationship between the occurrence of rainfalls after dry periods and an increase in the number of gastroenteritis cases and in HAdV load quantified in surface water collected for conventional potabilization.

  5. Human rotavirus group a serotypes causing gastroenteritis in ...

    African Journals Online (AJOL)

    Due to HIV/AIDS scourge in Kenya, it is possible that rotavirus-related gastroenteritis has been aggravated in adults. The Global Alliance for Immunizations has ranked rotavirus infection a priority for vaccine, and, to ensure its success, there is a need to document the local strain(s) circulating in different regions. Methods: A ...

  6. Economic costs of outbreaks of acute viral gastroenteritis due to norovirus in Catalonia (Spain), 2010-2011.

    Science.gov (United States)

    Navas, Encarna; Torner, Nuria; Broner, Sonia; Godoy, Pere; Martínez, Ana; Bartolomé, Rosa; Domínguez, Angela

    2015-10-01

    To determine the direct and indirect costs of outbreaks of acute viral gastroenteritis (AVG) due to norovirus in closed institutions (hospitals, social health centers or nursing homes) and the community in Catalonia in 2010-11. Information on outbreaks were gathered from the reports made by epidemiological surveillance units. Direct costs (medical visits, hospital stays, drug treatment, sample processing, transport, diagnostic tests, monitoring and control of the outbreaks investigated) and indirect costs (lost productivity due to work absenteeism, caregivers time and working hours lost due to medical visits) were calculated. Twenty-seven outbreaks affecting 816 people in closed institutions and 74 outbreaks affecting 1,940 people in the community were detected. The direct and indirect costs of outbreaks were € 131,997.36 (€ 4,888.79 per outbreak) in closed institutions and € 260,557.16 (€ 3,521.04 per outbreak) in community outbreaks. The cost per case was € 161.76 in outbreaks in closed institutions and € 134.31 in community outbreaks. The main costs were surveillance unit monitoring (€ 116,652.93), laboratory diagnoses (€ 119,950.95), transport of samples (€ 69,970.90), medical visits (€ 25,250.50) and hospitalization (€ 13,400.00). The cost of outbreaks of acute viral gastroenteritis due to norovirus obtained in this study was influenced by the number of people affected and the severity of the outbreak, which determined hospitalizations and work absenteeism. Urgent reporting of outbreaks would allow the implementation of control measures that could reduce the numbers affected and the duration of the illness and thus the costs derived from them.

  7. Clinical and epidemiological features of acute infantile gastroenteritis associated with human rotavirus subgroups 1 and 2.

    OpenAIRE

    Uhnoo, I; Svensson, L

    1986-01-01

    During a prospective 1-year study rotavirus isolates from 169 children with gastroenteritis were investigated by polyacrylamide gel electrophoresis. A total of 118 (70%) of the strains analyzed contained sufficient viral nucleic acid to give visible electrophoretic patterns; 36% were identified as strains belonging to subgroup 1 (short patterns), and 64% were identified as strains belonging to subgroup 2 (long patterns). The two subgroups cocirculated at equal frequencies during the first 7 m...

  8. Viral diseases and human evolution

    Directory of Open Access Journals (Sweden)

    Leal Élcio de Souza

    2000-01-01

    Full Text Available The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc. are becoming formidable challenges, which may have a direct impact on the fate of our species.

  9. Acute viral gastroenteritis in children hospitalized in Iksan, Korea during December 2010 - June 2011

    Directory of Open Access Journals (Sweden)

    Cheol Whoan So

    2013-09-01

    Full Text Available Purpose: Viral etiology is common in cases of children with acute diarrhea, and antibiotic therapy is usually not required. Therefore, it is important to determine the distribution of common viruses among children hospitalized with acute diarrhea. Methods: We included 186 children who suffered from acute diarrhea and were hospitalized at the Wonkwang University Hospital Pediatric ward from December 1, 2010 to June 30, 2011 in this study. Stool samples were collected and multiplex reverse transcriptase polymerase chain reaction (multiplex RT-PCR was used to simultaneously determine the viral etiology such as rotavirus, norovirus, astrovirus, or adenovirus.&lt;br&gt; Results: Causative viruses were detected in 72 of the 186 cases (38.7%. The mean age of the viruspositive cases was 1 year and 9 months (range, 1 month to 11 years. Rotavirus was detected in 50/186 (26.9%; norovirus, in 18/186 (9.7%; and astrovirus, in 3/186 cases (1.6%. Adenovirus was not detected in any of the cases. Proportions of norovirus genogroups I and II were 21.1% and 78.9%, respectively. Four of the 51 rotavirus-positive cases (7.8% had received rotavirus vaccination at least once. The mean duration of diarrhea was 2.8 days (range, 1 to 10 days and vomiting occurred in 39 of the 72 cases (54.2%.&lt;br&gt; Conclusion: Viral etiology was confirmed in about one-third of the children with acute diarrhea, and the most common viral agent was rotavirus, followed by norovirus.

  10. Norovirus drug candidates that inhibit viral capsid attachment to human histo-blood group antigens

    OpenAIRE

    Ali, Eunüs S.; Rajapaksha, Harinda; Carr, Jillian M.; Petrovsky, Nikolai

    2016-01-01

    Human noroviruses are the leading causative agents of epidemic and sporadic viral gastroenteritis and childhood diarrhoea worldwide. Human histo-blood group antigens (HBGA) serve as receptors for norovirus capsid protein attachment and play a critical role in infection. This makes HBGA-norovirus binding a promising target for drug development. Recently solved crystal structures of norovirus bound to HBGA have provided a structural basis for identification of potential anti-norovirus drugs and...

  11. Viral organization of human proteins.

    Directory of Open Access Journals (Sweden)

    Stefan Wuchty

    2010-08-01

    Full Text Available Although maps of intracellular interactions are increasingly well characterized, little is known about large-scale maps of host-pathogen protein interactions. The investigation of host-pathogen interactions can reveal features of pathogenesis and provide a foundation for the development of drugs and disease prevention strategies. A compilation of experimentally verified interactions between HIV-1 and human proteins and a set of HIV-dependency factors (HDF allowed insights into the topology and intricate interplay between viral and host proteins on a large scale. We found that targeted and HDF proteins appear predominantly in rich-clubs, groups of human proteins that are strongly intertwined among each other. These assemblies of proteins may serve as an infection gateway, allowing the virus to take control of the human host by reaching protein pathways and diversified cellular functions in a pronounced and focused way. Particular transcription factors and protein kinases facilitate indirect interactions between HDFs and viral proteins. Discerning the entanglement of directly targeted and indirectly interacting proteins may uncover molecular and functional sites that can provide novel perspectives on the progression of HIV infection and highlight new avenues to fight this virus.

  12. A novel RT-multiplex PCR for detection of Aichi virus, human parechovirus, enteroviruses, and human bocavirus among infants and children with acute gastroenteritis.

    Science.gov (United States)

    Pham, Ngan Thi Kim; Trinh, Quang Duy; Chan-It, Wisoot; Khamrin, Pattara; Shimizu, Hideaki; Okitsu, Shoko; Mizuguchi, Masashi; Ushijima, Hiroshi

    2010-10-01

    A novel reverse transcription-multiplex polymerase chain reaction assay was developed to detect Aichi virus, human parechovirus, enteroviruses, and human bocavirus. A mixture of four pairs of published specific primers, 6261 and 6779, ev22(+) and ev22(-), F1 and R1, 188F and 542R, was used to amplify the viral genomes and specifically generate four different amplicon sizes of 519, 270, 440, and 354 bp for Aichi virus, human parechovirus, enteroviruses, and human bocavirus, respectively. A total of 247 fecal specimens previously screened for rotavirus, adenovirus, norovirus, sapovirus, and astrovirus-negative, collected from infants and children with acute gastroenteritis in Japan from July 2007 to June 2008, were tested further for the presence of the four viruses, Aichi virus, human parechovirus, enteroviruses, and human bocavirus, by RT-multiplex PCR. The total detection rate of these viruses was 26.7% (66 out of 247 samples). Of these, HPeV, EVs, and HBoV were identified in 20, 41, and 5 specimens. No Aichi virus was found among these subjects. The sensitivity and specificity of RT-multiplex PCR were assessed and demonstrated a strong validation against RT-monoplex PCR. This is the first report of detecting these types of viruses in fecal samples from infants and children with acute gastroenteritis by RT-multiplex PCR. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  13. Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses and Vibrio cholerae

    Science.gov (United States)

    O’Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Salazar, Juan Carlos; Montero, David

    2015-01-01

    Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni. PMID:25715048

  14. Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses and Vibrio cholerae.

    Science.gov (United States)

    O'Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Salazar, Juan Carlos; Montero, David

    2015-01-01

    Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni.

  15. Human Parechovirus Infection in Children Hospitalized with Acute Gastroenteritis in Sri Lanka▿

    Science.gov (United States)

    Pham, Ngan Thi Kim; Takanashi, Sayaka; Tran, Dinh Nguyen; Trinh, Quang Duy; Abeysekera, Chandra; Abeygunawardene, Asiri; Khamrin, Pattara; Okitsu, Shoko; Shimizu, Hiroyuki; Mizuguchi, Masashi; Ushijima, Hiroshi

    2011-01-01

    Of 362 fecal specimens collected from infants and children hospitalized with acute gastroenteritis in Sri Lanka from September 2005 to August 2006, 30 (8.3%) were positive for human parechovirus (HPeV). Six different HPeV genotypes, including HPeV1, -3, -4, -5, -10, and -11, were identified, of these, HPeV11 was reported for the first time. PMID:21048003

  16. Metagenomic Analysis of Viruses in Feces from Unsolved Outbreaks of Gastroenteritis in Humans

    Science.gov (United States)

    Moore, Nicole E.; Wang, Jing; Hewitt, Joanne; Croucher, Dawn; Williamson, Deborah A.; Paine, Shevaun; Yen, Seiha; Greening, Gail E.

    2014-01-01

    The etiology of an outbreak of gastroenteritis in humans cannot always be determined, and ∼25% of outbreaks remain unsolved in New Zealand. It is hypothesized that novel viruses may account for a proportion of unsolved cases, and new unbiased high-throughput sequencing methods hold promise for their detection. Analysis of the fecal metagenome can reveal the presence of viruses, bacteria, and parasites which may have evaded routine diagnostic testing. Thirty-one fecal samples from 26 gastroenteritis outbreaks of unknown etiology occurring in New Zealand between 2011 and 2012 were selected for de novo metagenomic analysis. A total data set of 193 million sequence reads of 150 bp in length was produced on an Illumina MiSeq. The metagenomic data set was searched for virus and parasite sequences, with no evidence of novel pathogens found. Eight viruses and one parasite were detected, each already known to be associated with gastroenteritis, including adenovirus, rotavirus, sapovirus, and Dientamoeba fragilis. In addition, we also describe the first detection of human parechovirus 3 (HPeV3) in Australasia. Metagenomics may thus provide a useful audit tool when applied retrospectively to determine where routine diagnostic processes may have failed to detect a pathogen. PMID:25339401

  17. Cohort study of an outbreak of viral gastroenteritis in a nursing home for elderly, Majorca, Spain, February 2008.

    Science.gov (United States)

    Luque Fernández, M A; Galmés Truyols, A; Herrera Guibert, D; Arbona Cerdá, G; Sancho Gayá, F

    2008-12-18

    An outbreak of acute gastroenteritis occurred in a nursing home for elderly in Majorca between 4 and 23 February 2008. To know its aetiology and mechanism of transmission a retrospective cohort study was conducted with a fixed cohort including 146 people (96 residents and 50 employees). The data were collected from clinical histories and through a survey by questionnaire. In total 71 cases were identified (53 residents, 18 employees), corresponding to an overall attack rate (AR) of 48.6%.

  18. BEC, a Novel Enterotoxin of Clostridium perfringens Found in Human Clinical Isolates from Acute Gastroenteritis Outbreaks

    Science.gov (United States)

    Yonogi, Shinya; Matsuda, Shigeaki; Kawai, Takao; Yoda, Tomoko; Harada, Tetsuya; Kumeda, Yuko; Gotoh, Kazuyoshi; Hiyoshi, Hirotaka; Nakamura, Shota; Kodama, Toshio

    2014-01-01

    Clostridium perfringens is a causative agent of food-borne gastroenteritis for which C. perfringens enterotoxin (CPE) has been considered an essential factor. Recently, we experienced two outbreaks of food-borne gastroenteritis in which non-CPE producers of C. perfringens were strongly suspected to be the cause. Here, we report a novel enterotoxin produced by C. perfringens isolates, BEC (binary enterotoxin of C. perfringens). Culture supernatants of the C. perfringens strains showed fluid-accumulating activity in rabbit ileal loop and suckling mouse assays. Purification of the enterotoxic substance in the supernatants and high-throughput sequencing of genomic DNA of the strains revealed BEC, composed of BECa and BECb. BECa and BECb displayed limited amino acid sequence similarity to other binary toxin family members, such as the C. perfringens iota toxin. The becAB genes were located on 54.5-kb pCP13-like plasmids. Recombinant BECb (rBECb) alone had fluid-accumulating activity in the suckling mouse assay. Although rBECa alone did not show enterotoxic activity, rBECa enhanced the enterotoxicity of rBECb when simultaneously administered in suckling mice. The entertoxicity of the mutant in which the becB gene was disrupted was dramatically decreased compared to that of the parental strain. rBECa showed an ADP-ribosylating activity on purified actin. Although we have not directly evaluated whether BECb delivers BECa into cells, rounding of Vero cells occurred only when cells were treated with both rBECa and rBECb. These results suggest that BEC is a novel enterotoxin of C. perfringens distinct from CPE, and that BEC-producing C. perfringens strains can be causative agents of acute gastroenteritis in humans. Additionally, the presence of becAB on nearly identical plasmids in distinct lineages of C. perfringens isolates suggests the involvement of horizontal gene transfer in the acquisition of the toxin genes. PMID:24664508

  19. EVALUATION OF MURINE NOROVIRUS, FELINE CALICIVIRUS, POLIOVIRUS, AND MS2 AS SURROGATES FOR HUMAN NOROVIRUS IN a Model of Viral Persistence in SURFACE Water AND GROUNDWATER

    Science.gov (United States)

    Human noroviruses (NoV) are a significant cause of non bacterial gastroenteritis worldwide with contaminated drinking water a potential transmission route. The absence of a cell culture infectivity model for NoV necessitates the use of molecular methods and/or viral surrogate mod...

  20. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  1. Prevalence and molecular characterization of human rhinovirus in stool samples of individuals with and without acute gastroenteritis.

    Science.gov (United States)

    Khoonta, Prapaporn; Linsuwanon, Piyada; Posuwan, Nawarat; Vongpunsawad, Sompong; Payungporn, Sunchai; Poovorawan, Yong

    2017-05-01

    Human rhinovirus (RV) most often causes mild upper respiratory tract infection. Although RV is routinely isolated from the respiratory tract, few studies have examined RV in other types of clinical samples. The prevalence of RV was examined in 1,294 stool samples collected mostly from children with acute gastroenteritis residing in Bangkok and Khon Kaen province of Thailand between January 2010 and October 2014. In addition, 591 samples from hand-foot-mouth disease (HFMD) or herpangina patients who do not have gastroenteritis served as a comparison group. Samples were initially screened by semi-nested PCR for the RV 5'UTR through the VP2 capsid region. RV genotyping and phylogenetic analysis were performed on the VP4/VP2 regions. Among children with acute gastroenteritis, RV was found in 2.3% (30/1,294) of stool samples, which comprised 47% (14/30) RV-A, 17% (5/30) RV-B, and 37% (11/30) RV-C. In the comparison group, 0.8% (5/591) was RV-positive and RV-C (3/5) was the major species found. Interestingly, RV was recovered more often from children with acute gastroenteritis than from those with HFMD or herpangina. As many as 31 RV types were present in the gastroenteritis stools, which were different than the types found in those with HFMD or herpangina. J. Med. Virol. 89:801-808, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. A large outbreak of acute gastroenteritis caused by the human norovirus GII.17 strain at a university in Henan Province, China.

    Science.gov (United States)

    Huang, Xue-Yong; Su, Jia; Lu, Qian-Chao; Li, Shi-Zheng; Zhao, Jia-Yong; Li, Meng-Lei; Li, Yi; Shen, Xiao-Jing; Zhang, Bai-Fan; Wang, Hai-Feng; Mu, Yu-Jiao; Wu, Shu-Yu; Du, Yan-Hua; Liu, Li-Cheng; Chen, Wei-Jun; Klena, John David; Xu, Bian-Li

    2017-02-01

    Human noroviruses are a major cause of viral gastroenteritis and are the main etiological agents of acute gastroenteritis outbreaks. An increasing number of outbreaks and sporadic cases of norovirus have been reported in China in recent years. There was a large acute gastroenteritis outbreak at a university in Henan Province, China in the past five years. We want to identify the source, transmission routes of the outbreak by epidemiological investigation and laboratory testing in order to provide the effective control measures. The clinical cases were investigated, and analysed by descriptive epidemiological methods according to factors such as time, department, grade and so on. Samples were collected from clinical cases, healthy persons, the environment, water, and food at the university. These samples were tested for potential bacteria and viruses. The samples that tested positive for norovirus were selected for whole genome sequencing and the sequences were then analysed. From 4 March to 3 April 2015, a total of 753 acute diarrhoea cases were reported at the university; the attack rate was 3.29%. The epidemic curve showed two peaks, with the main peak occurring between 10 and 20 March, accounting for 85.26% of reported cases. The rates of norovirus detection in samples from confirmed cases, people without symptoms, and environmental samples were 32.72%, 17.39%, and 9.17%, respectively. The phylogenetic analysis showed that the norovirus belonged to the genotype GII.17. This is the largest and most severe outbreak caused by genotype GII.17 norovirus in recent years in China. The GII.17 viruses displayed high epidemic activity and have become a dominant strain in China since the winter of 2014, having replaced the previously dominant GII.4 Sydney 2012 strain.

  3. Incidence of Norovirus and Other Viral Pathogens That Cause Acute Gastroenteritis (AGE among Kaiser Permanente Member Populations in the United States, 2012-2013.

    Directory of Open Access Journals (Sweden)

    Scott P Grytdal

    Full Text Available Noroviruses and other viral pathogens are increasingly recognized as frequent causes of acute gastroenteritis (AGE. However, few laboratory-based data are available on the incidence of AGE caused by viral pathogens in the U.S. This study examined stool specimens submitted for routine clinical diagnostics from patients enrolled in Kaiser Permanente (KP health plans in metro Portland, OR, and the Maryland, District of Columbia, and northern Virginia geographic areas to estimate the incidence of viral enteropathogens in these populations. Over a one-year study period, participating laboratories randomly selected stools submitted for routine clinical diagnostics for inclusion in the study along with accompanying demographic and clinical data. Selected stools were tested for norovirus, rotavirus, sapovirus, and astrovirus using standardized real-time RT-PCR protocols. Each KP site provided administrative data which were used in conjunction with previously published data on healthcare utilization to extrapolate pathogen detection rates into population-based incidence rates. A total of 1,099 specimens collected during August 2012 to September 2013 were included. Mean age of patients providing stool specimens was 46 years (range: 0-98 years. Noroviruses were the most common viral pathogen identified among patients with AGE (n = 63 specimens, 6% of specimens tested. In addition, 22 (2% of specimens were positive for rotavirus; 19 (2% were positive for sapovirus; and 7 (1% were positive for astrovirus. Incidence of norovirus-associated outpatient visits was 5.6 per 1,000 person-years; incidence of norovirus disease in the community was estimated to be 69.5 per 1,000 person-years. Norovirus incidence was highest among children 65 years (outpatient incidence = 7.8 per 1,000 person-years; community incidence = 75.8 per 1,000 person-years. Outpatient incidence rates of rotavirus, sapovirus, and astrovirus were 2.0, 1.6, 0.6 per 1,000 person

  4. Characterisation of G8 human rotaviruses in Australian children with gastroenteritis.

    Science.gov (United States)

    Swiatek, Dayna L; Palombo, Enzo A; Lee, Alvin; Coventry, Michael J; Britz, Margaret L; Kirkwood, Carl D

    2010-03-01

    This study describes the characterisation of G8 rotavirus strains isolated from humans with acute gastroenteritis. Six G8 strains were detected in Australia between 2002 and 2008. Four were G8P[14] strains, one was G8P[8]+[14] and one was G8 P non-typeable. By polyacrylamide gel electrophoresis and enzyme immunoassay analysis, four G8 strains with visible RNA exhibited a long electropherotype and five G8 strains displayed subgroup I specificity. Sequence analysis of the VP7 gene indicated that the G8 strains exhibited the highest nucleotide and amino acid identity with a G8P[11] bovine rotavirus strain detected in Japan. VP4 sequence data of one G8P[14] strain revealed that the closest identity was to another human-bovine-like strain detected in Australia, MG6, a G6P[14] strain. The identification of G8 strains causing disease further extends the number of G8P[14] strains detected in Australian children, and indicates that there is a rare but ongoing presence of uncommon human strains within the community in Australia. Copyright 2009 Elsevier B.V. All rights reserved.

  5. An outbreak of Norwalk-like viral gastroenteritis in holidaymakers travelling to Andorra, January-February 2002.

    LENUS (Irish Health Repository)

    Pedalino, B

    2003-01-01

    A retrospective cohort study was conducted to investigate an outbreak of Norwalk-like viral gastroenteritidis that occurred in Irish holidaymakers visiting Andorra, in January-February 2002. Preliminary results showed the risk exposure was higher for tourists who stayed in Soldeu and consumed ice cubes in their drinks (OR = 2.5, 95% CI [1.3-4.6)], after logistic regression and adjusting for sex and water consumption).

  6. Estimating healthcare costs of acute gastroenteritis and human campylobacteriosis in Switzerland.

    Science.gov (United States)

    Schmutz, C; Mäusezahl, D; Bless, P J; Hatz, C; Schwenkglenks, M; Urbinello, D

    2017-03-01

    Rising numbers of campylobacteriosis case notifications in Switzerland resulted in an increased attention to acute gastroenteritis (AG) in general. Patients with a laboratory-confirmed Campylobacter infection perceive their disease as severe and around 15% of these patients are hospitalized. This study aimed at estimating healthcare costs due to AG and campylobacteriosis in Switzerland. We used official health statistics, data from different studies and expert opinion for estimating individual treatment costs for patients with different illness severity and for extrapolating overall costs due to AG and campylobacteriosis. We estimated that total Swiss healthcare costs resulting from these diseases amount to €29-45 million annually. Data suggest that patients with AG consulting a physician without a stool diagnostic test account for €9·0-24·2 million, patients with a negative stool test result for Campylobacter spp. for €12·3 million, patients testing positive for Campylobacter spp. for €1·8 million and hospitalized campylobacteriosis patients for €6·5 million/year. Healthcare costs of campylobacteriosis are high and most likely increasing in Switzerland considering that campylobacteriosis case notifications steadily increased in the past decade. Costs and potential cost savings for the healthcare system should be considered when designing sectorial and cross-sectorial interventions to reduce the burden of human campylobacteriosis in Switzerland.

  7. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine.

    Science.gov (United States)

    Herrera, Daniel; Vásquez, Camilo; Corthésy, Blaise; Franco, Manuel A; Angel, Juana

    2013-11-01

    Rotavirus (RV)-specific secretory immunoglobulin (RV-SIg) has been previously detected in serum of naturally RV infected children and shown to reflect the intestinal Ig immune response. Total plasma SIgA and plasma RV-SIg were evaluated by ELISA in children with gastroenteritis due or not due to RV infection and in 50 children vaccinated with the attenuated RIX4414 human RV vaccine and 62 placebo recipients. RV-SIg was only detected in children with evidence of previous RV infection or with acute RV gastroenteritis. Vaccinees had higher RV-SIg titers than placebo recipients and RV-SIg titers increased after the second vaccine dose. RV-SIg measured after the second dose correlated with protection when vaccinees and placebo recipients were analyzed jointly. RV-SIg may serve as a valuable correlate of protection for RV vaccines.

  8. Norovirus drug candidates that inhibit viral capsid attachment to human histo-blood group antigens.

    Science.gov (United States)

    Ali, Eunüs S; Rajapaksha, Harinda; Carr, Jillian M; Petrovsky, Nikolai

    2016-09-01

    Human noroviruses are the leading causative agents of epidemic and sporadic viral gastroenteritis and childhood diarrhoea worldwide. Human histo-blood group antigens (HBGA) serve as receptors for norovirus capsid protein attachment and play a critical role in infection. This makes HBGA-norovirus binding a promising target for drug development. Recently solved crystal structures of norovirus bound to HBGA have provided a structural basis for identification of potential anti-norovirus drugs and subsequently performed in silico and in vitro drug screens have identified compounds that block norovirus binding and may thereby serve as structural templates for design of therapeutic norovirus inhibitors. This review explores norovirus therapeutic options based on the strategy of blocking norovirus-HBGA binding. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Gravimetric Viral Diagnostics: : QCM Based Biosensors for Early Detection of Viruses

    NARCIS (Netherlands)

    Afzal, Adeel; Mujahid, Adnan; Schirhagl, Romana; Bajwa, Sadia Z.; Latif, Usman; Feroz, Saima

    2017-01-01

    Viruses are pathogenic microorganisms that can inhabit and replicate in human bodies causing a number of widespread infectious diseases such as influenza, gastroenteritis, hepatitis, meningitis, pneumonia, acquired immune deficiency syndrome (AIDS) etc. A majority of these viral diseases are

  10. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine

    OpenAIRE

    Herrera Daniel; Vásquez Camilo; Corthésy Blaise E.; Franco M. A.; Angel Juana

    2013-01-01

    Rotavirus (RV)-specific secretory immunoglobulin (RV-sIg) has been previously detected in serum of naturally RV infected children and shown to reflect the intestinal Ig immune response. Total plasma sIga and plasma RV-sIg were evaluated by eLIsa in children with gastroenteritis due or not due to RV infection and in 50 children vaccinated with the attenuated RIX4414 human RV vaccine and 62 placebo recipients. RV-sIg was only detected in children with evidence of previous RV infection or with a...

  11. Вocavirus infection in children with acute gastroenteritis

    Directory of Open Access Journals (Sweden)

    E. I. Krasnova

    2017-01-01

    Full Text Available The review presents the data on the most important causative factors of acute gastroenteritis in children and on relatively new pathogens, such as bocavirus (HBoV, considering modern potential for verification of viral disorders. Human HBoV, belonging to Parvoviridae family, has been isolated from nasopharyngeal discharge in children with acute respiratory viral infection in 2005. Later on it was registered as a respiratory pathogen. Despite symptoms of an acute respiratory disease, HBoVinfected patients frequently present with acute gastroenteritis. In various regions of the world, fecal HBoV DNA has been found in children with acute intestinal infection by means of the polymerase chain reaction and subsequent sequencing. Molecular genetic studies showed the presence of 4 genetically different viral types. HBoV genotype 1 is more frequently found in nasopharyngeal smears from children with acute respiratory viral infection, whereas HBoV genotypes 2, 3, and 4 are isolated from feces in those with acute gastroenteritis. If HBoV is an intestinal pathogen, remain an unresolved issue. There is a  high rate of HBoV co-infection (up to 60% and more with other intestinal viruses in children with acute gastroenteritis. High fecal DNA titers found in the studies in children with acute gastroenteritis have shown that HBoV is not only present in the bowel, but also is replicating there. The importance of studies on characteristics of molecular evolution of bocavirus is undoubted, while there are gaps in knowledge on its life cycle, mechanisms of genome replication; there is neither cultivation technique for this virus, nor animal models for disorders it may cause. The assay for anti-HBoV detection in human serum has been studied only in acute respiratory disease; high rates of HBoV seropositive patients and high antibody titers have been found in children correlating with a high viral load. It could be relevant to study prevalence and genetic variance

  12. Sensitive detection of viral transcripts in human tumor transcriptomes.

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    Sven-Eric Schelhorn

    Full Text Available In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates

  13. Epidemiology of human parechovirus, Aichi virus and salivirus in fecal samples from hospitalized children with gastroenteritis in Hong Kong.

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    Yip, Cyril C Y; Lo, Kin-Land; Que, Tak-Lun; Lee, Rodney A; Chan, Kwok-Hung; Yuen, Kwok-Yung; Woo, Patrick C Y; Lau, Susanna K P

    2014-10-18

    Emerging human picornaviruses, including human parechovirus (HPeV), Aichi virus (AiV) and salivirus (SalV) were found to be associated with gastroenteritis, but their roles in enteric infections are not fully understood. In addition, no report on the circulation of these viruses in Hong Kong is available. The objective of this study was to investigate the prevalence and genetic diversity of HPeV, AiV and SalV in fecal samples from hospitalized children with gastroenteritis in Hong Kong. Fecal samples from hospitalized children with gastroenteritis were subject to detection of HPeV, AiV and SalV by RT-PCR using consensus primers targeted to their 5'UTRs. Positive samples were subject to capsid and/or 3CD region analysis for genotype determination. The epidemiology of HPeV, AiV and SalV infections was analyzed. Among 1,708 fecal samples subjected to RT-PCR using primers targeted to 5'UTR of HPeV, AiV and SalV, viruses were detected in 55 samples, with 50 positive for HPeV only, 3 positive for AiV only, 1 positive for both HPeV and AiV, and 1 positive for both HPeV and SalV. Phylogenetic analysis of the partial VP1 gene of the 33 HPeV strains revealed the presence of genotypes of HPeV- 1, 3, 4, 5, 7, 10, among which HPeV-1 was the predominant genotype circulating in our population. The peak activity of HPeV infection was in fall. Of the 3 children with AiV infection, the 3 AiV strains were found to belong to genotype A based on the phylogenetic analysis of their partial VP1 and 3CD regions. The genotype of a SalV strain detected in this study could not be determined. Co-detection of different pathogens was observed in 24 samples (43.6%) of 55 fecal samples positive for HPeV, AiV and SalV. HPeV, AiV and SalV were detected in fecal samples of hospitalized children with gastroenteritis in Hong Kong, with the former having the highest prevalence. HPeV-1 was the predominant genotype among HPeVs, while genotype A was the predominant genotype among AiVs in this study.

  14. Gastroenteritis: First Aid

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    First aid Gastroenteritis: First aid Gastroenteritis: First aid By Mayo Clinic Staff Gastroenteritis is an inflammation of your stomach and intestines. Common causes are: Viruses. Food or water contaminated by ...

  15. Epidemiological aspects of human rotavirus infection in children hospitalized with acute gastroenteritis in an area of northern Italy.

    Science.gov (United States)

    Medici, Maria Cristina; Martinelli, Monica; Arcangeletti, Maria Cristina; Pinardi, Federica; De Conto, Flora; Dodi, Icilio; Virdis, Raffaele; Abelli, Laura Anna; Aloisi, Annalisa; Zerbini, Laura; Valcavi, Pierpaolo; Calderaro, Adriana; Bernasconi, Sergio; Izzi, Gian Carlo; Dettori, Giuseppe; Chezzi, Carlo

    2004-08-01

    Human rotavirus (HRV) is recognized as the most common cause of severe gastroenteritis in children under 5 years of age. Due to the lack of recent reports about the surveillance of HRV infection in Italy, in this study we assessed the prevalence rate of HRV infection on 1,340 stool samples belonging to 1,264 pediatric patients hospitalized with acute gastroenteritis in the period January 2000--December 2002. The stool samples were submitted to virological investigations by electron microscopy (EM) and conventional cell culture, as well as from January 2002 by RT-PCR for norovirus detection. Reovirus-like particles observed by EM were identified by electropherotyping. Single HRV infections were detected in 302 cases (23.9%, ranging from 19.1% in 2000 to 30.2% in 2001). Mixed infections were observed in 28 cases in which HRV was found to be associated with adenovirus in 16 cases (1.3%), with picornavirus in 4 (0.3%), and with norovirus in 8 (2.1% of the 388 cases examined in 2002). The 3 major epidemic periods of HRV infections were March--May 2000 (66 cases), December 2000--May 2001 (128 cases) and September 2001--April 2002 (105 cases) with peaks in March, January and March, and January, respectively. In the periods of major incidence, single HRV infection accounted even for 52.5% of the gastroenteritis cases monthly examined. According to age distribution, 68.9% (208 cases) of HRV infected children was under 4 years (69.6%: 230/330 cases, including mixed infections) and 16.9% (51 cases) was in the 5-12-year age-group. The epidemiological aspects of HRV infection, also compared to other enteric virus infections, will contribute to assess the magnitude of the problem of HRV in different settings and to devise strategies for intervention.

  16. Rotavirus gastroenteritis.

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    Leung, A K; Pai, C H

    1988-01-01

    Rotavirus gastroenteritis is a leading cause of morbidity and mortality, especially in developing countries. Dehydration, which is often isotonic, occurs in 40 to 80% of patients. Rehydration and maintenance of proper fluid and electrolyte balance remains the mainstay of treatment. In recent years, development of efficient diagnostic methods has led to better understanding of the morphology of the virus, the epidemiology and natural history, as well as the importance of rotavirus disease. Rapid progress in the development and improvement of rotavirus vaccines has also been made. Among the vaccine candidates currently available, both the bovine rotavirus strain RIT 4237 and the rhesus rotavirus strain MMU 18006 have undergone extensive clinical trials and both have shown promising results.

  17. Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent.

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    Li, Linlin; Deng, Xutao; Mee, Edward T; Collot-Teixeira, Sophie; Anderson, Rob; Schepelmann, Silke; Minor, Philip D; Delwart, Eric

    2015-03-01

    Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries were compared for their abilities to detect multiple viruses and generate full genome coverage. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. EOSINOPHILIC GASTROENTERITIS

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    Borut Štabuc

    2003-07-01

    Full Text Available Background. Eosinophilic gastroenteritis (EGE is a rare disorder of unknown etiology, characterised by infiltrating eosinophils into one or more layers of gastrointestinal tract and various gastrointestinal manifestations. Signs and symptoms are related to the layer and extent of bowel involved with eosinophilic infiltration bowel with mucosa, muscle, subserosa or all three affected. Steroid therapy remains the corner stone of treatment.Patients and methods. This paper describes a case of 70-yearold male patient with eosinophilic mucosal disease of upper intestinal wall repeatedly admitted because of epigastralgias, nausea, vomiting and losing weight. Because of hypereosinophilia, a biopsy of duodenal mucosa was performed, despite the normal endoscopic appearance. Numerous eosinophilic infiltrates were histologically confirmed in mucosa and submucosa and remission followed metilprednisolon therapy.Results. After two years signs of ilness reapearred, and again metilprednisolon therapy was followed by remission which still last.Conclusions. EGE needs to be recognized by the clinician because it can masquerade as the irritable bowel syndrome. The diagnosis of EGE is confirmed by a characteristic biopsy. Treatment is empiric and gauged to the severity of the clinical manifestations.

  19. Evaluation and molecular characterization of human adenovirus in drinking water supplies: viral integrity and viability assays.

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    Fongaro, Gislaine; Nascimento, Mariana A do; Rigotto, Caroline; Ritterbusch, Giseli; da Silva, Alessandra D' A; Esteves, Paulo A; Barardi, Célia R M

    2013-05-28

    Human adenoviruses (HAdVs) are the second-leading cause of childhood gastroenteritis worldwide. This virus is commonly found in environmental waters and is very resistant to water disinfection and environmental stressors, especially UV light inactivation. Molecular techniques, such as PCR-based methods (Polymerase Chain Reaction), are commonly used to detect and identify viral contamination in water, although PCR alone does not allow the discrimination between infectious and non-infectious viral particles. A combination of cell culture and PCR has allowed detection of infectious viruses that grow slowly or fail to produce cytopathic effects (CPE) in cell culture. This study aimed to assess the integrity and viability of human adenovirus (HAdV) in environmental water and evaluate circulating strains by molecular characterization in three sites of the water supply in Florianópolis, Santa Catarina Island, Brazil: Peri Lagoon water, spring source water, and water from the public water supply system. Water samples were collected, concentrated and HAdV quantified by real-time PCR. Viral integrity was evaluated by enzymatic assay (DNase I) and infectivity by plaque assay (PA) and integrated cell culture using transcribed mRNA (ICC-RT-qPCR). Samples containing particles of infectious HAdV were selected for sequencing and molecular characterization. The analyzed sites contained 83, 66 and 58% undamaged HAdV particles (defined as those in which the genetic material is protected by the viral capsid) at Peri Lagoon, spring source water and public supply system water, respectively. Of these, 66% of the particles (by PA) and 75% (by ICC-RT-qPCR) HAdV were shown to be infectious, due to being undamaged in Peri Lagoon, 33% (by PA) and 58% (by ICC-RT-qPCR) in spring source water and 8% (by PA) and 25% (by ICC-RT-qPCR) in the public water supply system. ICC-RT-qPCR, a very sensitive and rapid technique, was able to detect as low as 1 × 102 HAdV genome copies per milliliter of

  20. ABO blood grouping in Egyptian children with rotavirus gastroenteritis.

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    Elnady, Hala Gouda; Abdel Samie, Ola M; Saleh, Maysa Tawhid; Sherif, Lobna S; Abdalmoneam, Naglaa; Kholoussi, Naglaa M; Kholoussi, Shams M; El-Taweel, Ahmed N

    2017-01-01

    Rotavirus gastroenteritis is an important public health problem all over the world, causing a notable economic burden in both developing and developed countries. To explore the relationship between blood group typing, rotavirus gastroenteritis, and its severity in Egyptian children. A cross sectional case control study was conducted on 231 cases of acute gastroenteritis attending the outpatient clinic of Al-Zahraa University Hospital. Full history taking, clinical examination, and clinical data collection were done. Blood samples were collected for an ABO grouping. Stool samples were tested for viral gastroenteritis agents. Rota positive cases of GE were significantly more prevalent among cases with blood group A (p fever (p rotavirus gastroenteritis. This could highlight an important risk factor, which could play a significant role for the pathogenesis of rotavirus gastroenteritis and severity as well. Furthermore, more intervention care could be needed for blood group A paediatric patients, if gastroenteritis especially rotavirus affect this group to avoid comorbidities.

  1. High frequency of cultivable human subgroup F adenoviruses in stool samples from a paediatric population admitted to hospital with acute gastroenteritis.

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    Arcangeletti, Maria-Cristina; Germini, Diego; Martorana, Davide; Rodighiero, Isabella; De Conto, Flora; Medici, Maria-Cristina; Chezzi, Carlo; Calderaro, Adriana

    2014-06-01

    The family Adenoviridae consists of five genera of which the genus Mastadenovirus includes human viruses classified into 57 serotypes clustered into seven subgroups (A-G). Serotypes 40 and 41 (subgroup F) are specifically associated with childhood gastroenteritis and are the most common cause of acute gastroenteritis in young children after rotaviruses and noroviruses. Standard methods for laboratory diagnosis of adenovirus infection include electron microscopy (EM) and conventional cell culture (CCC), although it is widely considered that adenoviruses 40 and 41 are difficult to cultivate, such that their circulation is most likely underestimated. One hundred and ten faecal specimens from paediatric patients with gastroenteritis were confirmed positive for adenovirus by EM and/or CCC at the Virology Unit of the University Hospital of Parma, Italy, during the period January 2010-December 2012. They were analysed to determine the actual prevalence of adenovirus 40 and 41 in these patients using PCR and restriction endonuclease analysis, and to evaluate their ability to be cultivated in standard cell lines. The results showed a high prevalence of subgroup F (62.7 %), with serotype 41 (89.8 %) predominating over serotype 40 (10.2 %). Surprisingly, among the 75 adenoviruses isolated by CCC, 37 (49 %) belonged to subgroup F, suggesting a higher capacity of adenovirus 40 and 41 to replicate in cell culture than previously thought. PCR and restriction enzyme techniques provide an efficient means of diagnosing enteric adenoviruses correctly, including subgroup F adenovirus strains in young children with gastroenteritis. © 2014 The Authors.

  2. Impact of high coverage of monovalent human rotavirus vaccine on Emergency Department presentations for rotavirus gastroenteritis.

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    Davey, Heather M; Muscatello, David J; Wood, James G; Snelling, Thomas L; Ferson, Mark J; Macartney, Kristine K

    2015-03-30

    Australia was one of the first countries to introduce nationally funded rotavirus vaccination. The program has had a substantial impact on both rotavirus and all-cause acute gastroenteritis (AGE) hospitalisations and rotavirus laboratory tests. Evidence for an impact on Emergency Department (ED) presentations is limited. This study assessed changes in ED presentations for rotavirus in children aged rotavirus vaccine (RV1, Rotarix(®), GlaxoSmithKline Australia Pty Ltd., Victoria, Australia). A time series analysis to examine trends in total non-admitted ED presentations for all-cause AGE and in the rotavirus-attributable fraction using data on rotavirus positive laboratory tests. A decline in the rate of non-admitted ED presentations for all-cause AGE was observed for all ages, being most notable in 1 year old children. Compared with the pre-vaccination period, we estimated the average weekly rate was lower across the first 4.5 years of the program for both all-cause AGE (18.3%; 70.5 versus 57.5 per 100,000 population) and rotavirus attributable (55.4%; 17.3 versus 7.7 per 100,000 population) presentations. In the fourth year of the program, estimated annual rotavirus attributable presentations were 77% lower than the pre-vaccination annual mean (996 versus 4300 per year). The program was associated with a substantial decline in rotavirus attributable non-admitted AGE presentations to ED among children aged <5 years. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  3. Association between living environment and human oral viral ecology.

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    Robles-Sikisaka, Refugio; Ly, Melissa; Boehm, Tobias; Naidu, Mayuri; Salzman, Julia; Pride, David T

    2013-09-01

    The human oral cavity has an indigenous microbiota known to include a robust community of viruses. Very little is known about how oral viruses are spread throughout the environment or to which viruses individuals are exposed. We sought to determine whether shared living environment is associated with the composition of human oral viral communities by examining the saliva of 21 human subjects; 11 subjects from different households and 10 unrelated subjects comprising 4 separate households. Although there were many viral homologues shared among all subjects studied, there were significant patterns of shared homologues in three of the four households that suggest shared living environment affects viral community composition. We also examined CRISPR (clustered regularly interspaced short palindromic repeat) loci, which are involved in acquired bacterial and archaeal resistance against invading viruses by acquiring short viral sequences. We analyzed 2 065 246 CRISPR spacers from 5 separate repeat motifs found in oral bacterial species of Gemella, Veillonella, Leptotrichia and Streptococcus to determine whether individuals from shared living environments may have been exposed to similar viruses. A significant proportion of CRISPR spacers were shared within subjects from the same households, suggesting either shared ancestry of their oral microbiota or similar viral exposures. Many CRISPR spacers matched virome sequences from different subjects, but no pattern specific to any household was found. Our data on viromes and CRISPR content indicate that shared living environment may have a significant role in determining the ecology of human oral viruses.

  4. Complete Genome Analysis of a Rabbit Rotavirus Causing Gastroenteritis in a Human Infant

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    Melisa Berenice Bonica

    2015-02-01

    Full Text Available Group A rotaviruses (RVA are responsible for causing infantile diarrhea both in humans and animals. The molecular characteristics of lapine RVA strains are only studied to a limited extent and so far G3P[14] and G3P[22] were found to be the most common G/P-genotypes. During the 2012-2013 rotavirus season in Belgium, a G3P[14] RVA strain was isolated from stool collected from a two-year-old boy. We investigated whether RVA/Human-wt/BEL/BE5028/2012/G3P[14] is completely of lapine origin or the result of reassortment event(s. Phylogenetic analyses of all gene segments revealed the following genotype constellation: G3-P[14]-I2-R2-C2-M3-A9-N2-T6-E5-H3 and indicated that BE5028 probably represents a rabbit to human interspecies transmission able to cause disease in a human child. Interestingly, BE5028 showed a close evolutionary relationship to RVA/Human-wt/BEL/B4106/2000/G3P[14], another lapine-like strain isolated in a Belgian child in 2000. The phylogenetic analysis of the NSP3 segment suggests the introduction of a bovine(-like NSP3 into the lapine RVA population in the past 12 years. Sequence analysis of NSP5 revealed a head-to-tail partial duplication, combined with two short insertions and a deletion, indicative of the continuous circulation of this RVA lineage within the rabbit population.

  5. CMV - gastroenteritis/colitis

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    Colitis - cytomegalovirus; Gastroenteritis - cytomegalovirus; Gastrointestinal CMV disease ... or after bone marrow or organ transplant Ulcerative colitis or Crohn disease Rarely, serious CMV infection involving ...

  6. The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study.

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    Monika Jevšnik

    Full Text Available Human coronaviruses (HCoVs are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB, acute gastroenteritis (AGE, or febrile seizures (FS, and children admitted for elective surgical procedures (healthy controls were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9.9%, 95% CI: 6-15%, followed by children with AGE (19/218, 8.7%, 95% CI: 5.3-13.3% and AB (20/308, 6.5%, 95% CI: 4.0-9.8%. The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1-99.8%, followed by FS (10/19, 52.6%, 95% CI: 28.9-75.6% and AGE (7/19, 36.8%, 95% CI: 16.3-61.6%. In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4-5.5% NP swabs and 1/150 (0.7%, 95% CI: 0.02-3.3% stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%.ClinicalTrials.gov NCT00987519.

  7. Identification of Human Bocavirus type 4 in a child asymptomatic for respiratory tract infection and acute gastroenteritis – Goiânia, Goiás, Brazil

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    Teresinha Teixeira de Sousa

    2017-07-01

    The aim of this study was to detect and characterize HBoV from fecal samples collected from hospitalized children aged less than five years old with no symptoms of respiratory tract infection (RTI or acute gastroenteritis (AGE. The study involved 119 children and one fecal sample was collected from each participant between 2014 and 2015. HBoV was detected using Nested-PCR, and the viral type identified by genomic sequencing. HBoV-4 was identified from one sample obtained from a hospitalized child with soft tissue tumor of the submandibular region. This is the first report of HBoV-4 identification in Brazil, but we consider that this type may be circulating in the country similar to the other types and new investigations are necessary.

  8. Extension of the viral ecology in humans using viral profile hidden Markov models.

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    Bzhalava, Zurab; Hultin, Emilie; Dillner, Joakim

    2018-01-01

    When human samples are sequenced, many assembled contigs are "unknown", as conventional alignments find no similarity to known sequences. Hidden Markov models (HMM) exploit the positions of specific nucleotides in protein-encoding codons in various microbes. The algorithm HMMER3 implements HMM using a reference set of sequences encoding viral proteins, "vFam". We used HMMER3 analysis of "unknown" human sample-derived sequences and identified 510 contigs distantly related to viruses (Anelloviridae (n = 1), Baculoviridae (n = 34), Circoviridae (n = 35), Caulimoviridae (n = 3), Closteroviridae (n = 5), Geminiviridae (n = 21), Herpesviridae (n = 10), Iridoviridae (n = 12), Marseillevirus (n = 26), Mimiviridae (n = 80), Phycodnaviridae (n = 165), Poxviridae (n = 23), Retroviridae (n = 6) and 89 contigs related to described viruses not yet assigned to any taxonomic family). In summary, we find that analysis using the HMMER3 algorithm and the "vFam" database greatly extended the detection of viruses in biospecimens from humans.

  9. Viral communities associated with human pericardial fluids in idiopathic pericarditis.

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    Laura Fancello

    Full Text Available Pericarditis is a common human disease defined by inflammation of the pericardium. Currently, 40% to 85% of pericarditis cases have no identified etiology. Most of these cases are thought to be caused by an infection of undetected, unsuspected or unknown viruses. In this work, we used a culture- and sequence-independent approach to investigate the viral DNA communities present in human pericardial fluids. Seven viral metagenomes were generated from the pericardial fluid of patients affected by pericarditis of unknown etiology and one metagenome was generated from the pericardial fluid of a sudden infant death case. As a positive control we generated one metagenome from the pericardial fluid of a patient affected by pericarditis caused by herpesvirus type 3. Furthermore, we used as negative controls a total of 6 pericardial fluids from 6 different individuals affected by pericarditis of non-infectious origin: 5 of them were sequenced as a unique pool and the remaining one was sequenced separately. The results showed a significant presence of torque teno viruses especially in one patient, while herpesviruses and papillomaviruses were present in the positive control. Co-infections by different genotypes of the same viral type (torque teno viruses or different viruses (herpesviruses and papillomaviruses were observed. Sequences related to bacteriophages infecting Staphylococcus, Enterobacteria, Streptococcus, Burkholderia and Pseudomonas were also detected in three patients. This study detected torque teno viruses and papillomaviruses, for the first time, in human pericardial fluids.

  10. Viral communities associated with human pericardial fluids in idiopathic pericarditis.

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    Fancello, Laura; Monteil, Sonia; Popgeorgiev, Nikolay; Rivet, Romain; Gouriet, Frédérique; Fournier, Pierre-Edouard; Raoult, Didier; Desnues, Christelle

    2014-01-01

    Pericarditis is a common human disease defined by inflammation of the pericardium. Currently, 40% to 85% of pericarditis cases have no identified etiology. Most of these cases are thought to be caused by an infection of undetected, unsuspected or unknown viruses. In this work, we used a culture- and sequence-independent approach to investigate the viral DNA communities present in human pericardial fluids. Seven viral metagenomes were generated from the pericardial fluid of patients affected by pericarditis of unknown etiology and one metagenome was generated from the pericardial fluid of a sudden infant death case. As a positive control we generated one metagenome from the pericardial fluid of a patient affected by pericarditis caused by herpesvirus type 3. Furthermore, we used as negative controls a total of 6 pericardial fluids from 6 different individuals affected by pericarditis of non-infectious origin: 5 of them were sequenced as a unique pool and the remaining one was sequenced separately. The results showed a significant presence of torque teno viruses especially in one patient, while herpesviruses and papillomaviruses were present in the positive control. Co-infections by different genotypes of the same viral type (torque teno viruses) or different viruses (herpesviruses and papillomaviruses) were observed. Sequences related to bacteriophages infecting Staphylococcus, Enterobacteria, Streptococcus, Burkholderia and Pseudomonas were also detected in three patients. This study detected torque teno viruses and papillomaviruses, for the first time, in human pericardial fluids.

  11. Viral hepatitis E: A disease of humans and animals

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    Kureljušić Branislav

    2012-01-01

    Full Text Available The hepatitis E virus is ubiquitous in all parts of the world where pig production exists. The infection occurs in several animal species and its course is mostly asymptomatic. Viral strains isolated from pigs and humans are genetically similar, which indicates a potential zoonotic nature of the disease, and the possibility that pigs, and perhaps also other species of animals diseased with viral hepatitis E are a source of infection to humans. The pig hepatitis E virus, which is similar to the hepatitis E virus in humans, was isolated and described for the first time in the USA in 1997. The infection of pigs with hepatitis E virus occurs through faeco-oral transmission, by ingestion of feed and water contaminated with the virus, or through direct contact between infected and healthy animals. The pathogenesis of this infection in pigs differs from its pathogenesis in humans and it has not been sufficiently examined in all its aspects. Even though viral hepatitis E in pigs has been described as a subclinical disease, some authors describe changes in the concentration of certain biochemical parameters in blood serum of the infected pigs. Histologically, a mild to moderate lymphotic-plasma cellular infiltration is observed in livers of infected pigs, as well as focal areas of hepatocyte necrosis. Viral hepatitis E is an endemic disease of humans in Asia, Africa, and Latin America. In developed countries, hepatitis E sporadically occurs in humans, but it is becoming of increasing importance in particular in Japan, North America, and Europe, because the populations of these areas travel extensively to the endemic regions or as a result of the consumption of thermally untreated meat of wild boar and products made from thermally untreated meat. Pork products can be contaminated with hepatitis E virus. Further proof that indicates the zoonotic potential of this virus and places this diseases among the group of professional diseases of farmers and

  12. Epidemiology of Acute Gastroenteritis Outbreaks Caused by Human Calicivirus (Norovirus and Sapovirus) in Catalonia: A Two Year Prospective Study, 2010-2011.

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    Torner, Nuria; Martinez, Ana; Broner, Sonia; Moreno, Antonio; Camps, Neus; Domínguez, Angela

    2016-01-01

    The epidemiology of cases of acute gastroenteritis (AGE) of viral etiology is a relevant public health issue. Due to underreporting, the study of outbreaks is an accepted approach to investigate their epidemiology. The objective of this study was to investigate the epidemiological characteristics of AGE outbreaks due to norovirus (NoV) and sapovirus (SV) in Catalonia. Prospective study of AGE outbreaks of possible viral etiology notified during two years in Catalonia. NoV and SV were detected by real time reverse transcription polymerase (RT-PCR). A total of 101 outbreaks were registered affecting a total of 2756 persons and 12 hospitalizations (hospitalization rate: 0.8x1,000,000 persons-year); 49.5% of outbreaks were foodborne, 45.5% person to person and 5% waterborne. The distribution of outbreaks according to the setting showed a predominance of catering services (39.6%), nursing homes and long term care facilities (26.8%) and schools (11.9%). The median number of cases per outbreak was 17 (range 2-191). The total Incidence rate (IR) was 18.3 per 100,000 persons-years (95%CI: 17.6-19.0). The highest IR was in persons aged ≥65 years (43.6x100,000 (95% CI: 41.0-46.2)) (p<0.001). A total of 1065 samples were analyzed with a positivity rate of 60.8%. 98% of positive samples were NoV (GII 56.3%; GI 4.2%; GII+GI 4.2%; non- typable 33.0%). SV was identified in two person-to-person transmission outbreaks in children. These results confirm the relevance of viral AGE outbreaks, both foodborne and person-to-person, especially in institutionalized persons. SV should be taken into account when investigating viral AGE outbreaks.

  13. Epidemiology of Acute Gastroenteritis Outbreaks Caused by Human Calicivirus (Norovirus and Sapovirus in Catalonia: A Two Year Prospective Study, 2010-2011.

    Directory of Open Access Journals (Sweden)

    Nuria Torner

    Full Text Available The epidemiology of cases of acute gastroenteritis (AGE of viral etiology is a relevant public health issue. Due to underreporting, the study of outbreaks is an accepted approach to investigate their epidemiology. The objective of this study was to investigate the epidemiological characteristics of AGE outbreaks due to norovirus (NoV and sapovirus (SV in Catalonia.Prospective study of AGE outbreaks of possible viral etiology notified during two years in Catalonia. NoV and SV were detected by real time reverse transcription polymerase (RT-PCR.A total of 101 outbreaks were registered affecting a total of 2756 persons and 12 hospitalizations (hospitalization rate: 0.8x1,000,000 persons-year; 49.5% of outbreaks were foodborne, 45.5% person to person and 5% waterborne. The distribution of outbreaks according to the setting showed a predominance of catering services (39.6%, nursing homes and long term care facilities (26.8% and schools (11.9%. The median number of cases per outbreak was 17 (range 2-191. The total Incidence rate (IR was 18.3 per 100,000 persons-years (95%CI: 17.6-19.0. The highest IR was in persons aged ≥65 years (43.6x100,000 (95% CI: 41.0-46.2 (p<0.001. A total of 1065 samples were analyzed with a positivity rate of 60.8%. 98% of positive samples were NoV (GII 56.3%; GI 4.2%; GII+GI 4.2%; non- typable 33.0%. SV was identified in two person-to-person transmission outbreaks in children.These results confirm the relevance of viral AGE outbreaks, both foodborne and person-to-person, especially in institutionalized persons. SV should be taken into account when investigating viral AGE outbreaks.

  14. Analysis of Aichi virus and Saffold virus association with pediatric acute gastroenteritis.

    Science.gov (United States)

    Li, Li-Li; Liu, Na; Yu, Jei-Mei; Ao, Yuan-Yun; Li, Shan; Stine, O Colin; Duan, Zhao-Jun

    2017-02-01

    Aichi virus (AiV) and Saffold virus (SAFV) have been reported in children with acute gastroenteritis and respiratory disease worldwide; however, their causative role in acute gastroenteritis remains ambiguous. To assess the clinical association of AiV and SAFV with acute gastroenteritis in the pediatric population. A case-control study involving 461 paired stool samples from pediatric cases with diarrhea and healthy controls was conducted in China. Quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) was used to screen AiV and SAFV. In the 461 paired samples, AiV and SAFV were more prevalent among asymptomatic children than children with acute gastroenteritis (0.87% vs. 0.43% and 2.8% vs. 1.5%, respectively), with no significant differences between groups (p=0.142 and p=0.478, respectively). Cox regression model analysis revealed no correlation between AiV (odds ratio, OR=2.24; 95% confidence interval, CI, 0.76-6.54) or SAFV infection (OR=1.36; 95% CI, 0.86-2.15) and diarrhea. High viral loads were found in both AiV- and SAFV-positive groups, with no significant difference in viral load between the groups (p=0.507 and p=0.677, respectively). No other known enteric pathogens were found in the AiV-positive samples but common in SAFV-positive cases. Phylogenetic analysis revealed that all 6 AiV subjects clustered with genotype B. All 7 SAFV-positive cases and 8 of 13 SAFV-positive controls were genotyped successfully; the genotypes identified included SAFV-1, SAFV-2 SAFV-3, and SAFV-6. Our study revealed no association of these viruses in acute gastroenteritis in children. These viruses may have the ability to replicate in humans; however, the infections are usually asymptomatic. Copyright © 2016. Published by Elsevier B.V.

  15. Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomised, double-blind, placebo controlled trial

    Science.gov (United States)

    Cunliffe, Nigel A; Witte, Desiree; Ngwira, Bagrey M; Todd, Stacy; Bostock, Nancy J; Turner, Ann M; Chimpeni, Philips; Victor, John C; Steele, A Duncan; Bouckenooghe, Alain; Neuzil, Kathleen M

    2014-01-01

    Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children. A phase III, placebo-controlled, multi-centre clinical trial of a live, oral G1P[8] human rotavirus vaccine (RIX4414) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life. We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life. A total of 1,773 healthy infants were enrolled in Blantyre, Malawi into three groups. Two groups received three doses of RIX4414 or placebo at age 6, 10, and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks. Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age, and were then re-consented for further follow-up to 18-24 months of age. Severity of gastroenteritis episodes was graded according to the Vesikari scoring system. Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre- and post-vaccine blood samples. Rotavirus VP7 (G) and VP4 (P) genotypes were determined by RT-PCR. A total of 70/1030 (6.8%, 95% CI 5.3 - 8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3 – 14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (Vaccine Efficacy 38.1% (9.8 – 57.3). The point estimate of efficacy in the second year of life (17.6%; −59.2 – 56.0) was lower than in the first year of life (49.4%; 19.2 – 68.3). There were non-significant trends towards a higher efficacy in the second year of life among children who received the three-dose schedule compared with the two-dose schedule, and a higher anti-rotavirus IgA seroresponse rate in the three-dose RIX4414 group. Rotavirus strains detected included genotype G12 (31%); G9 (23%); and G8 (18%); only 18% of strains belonged

  16. Lactoferrin for prevention of common viral infections.

    Science.gov (United States)

    Wakabayashi, Hiroyuki; Oda, Hirotsugu; Yamauchi, Koji; Abe, Fumiaki

    2014-11-01

    Although lactoferrin has many biological functions, the host-protective effects against pathogenic microorganisms including bacteria, fungi, and viruses are regarded as one of the most important. Here, we review research on the protective role of lactoferrin administration against common viral infections. Many studies have shown the in vitro antiviral activity of lactoferrin against viral pathogens that cause common infections such as the common cold, influenza, gastroenteritis, summer cold, and herpes, where lactoferrin inhibits mainly viral attachment to the target cells. Recently, studies indicating the in vivo protective effects of lactoferrin by oral administration against common viral infections have been increasing. For instance, norovirus is an extremely important emerging human pathogen that causes a majority of gastroenteritis outbreaks worldwide that may be a target candidate for lactoferrin. Lactoferrin consumption reduced the incidence of noroviral gastroenteritis in children and a similar effect was observed in a wide range of ages in a preliminary survey. A recent in vitro study reported that lactoferrin inhibits both cellular attachment of the murine norovirus, a virus closely-related to the human norovirus, and viral replication in the cells by inducing antiviral cytokines interferon (IFN)-α/β. Lactoferrin administration also enhances NK cell activity and Th1 cytokine responses, which lead to protection against viral infections. In conclusion, lactoferrin consumption may protect the host from viral infections through inhibiting the attachment of a virus to the cells, replication of the virus in the cells, and enhancement of systemic immune functions. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. Generation and maintenance of human memory cells during viral infection.

    Science.gov (United States)

    Halwani, Rabih; Doroudchi, Mehrnoosh; Yassine-Diab, Bader; Janbazian, Loury; Shi, Yu; Said, Elias A; Haddad, Elias K; Sékaly, Rafick-Pierre

    2006-11-01

    Long-term maintenance of memory T cell response is the hallmark of immune protection and hence the holy grail of most vaccine development studies. Persistent memory cells, developed after either viral infection or vaccination, ensure the generation of an antiviral response upon reexposure to the pathogen. During acute viral infections, as in the case of measles and influenza viruses, strong T cell effector functions, which eradicate the virus and protect patients against reexposure, are achieved by the generation of persistent protective memory cells. However, in chronic infections, T cells drastically lose effector functions before acquiring a memory phenotype. Chronic infections can be categorized into infections where viremia is controlled and protective memory cells are maintained as in the case of EBV and CMV infections, or where the virus persists and memory cells are exhausted and disrupted as in the case of human immunodeficiency virus infection. In this review, we will discuss the different phenotypical and functional characteristics of memory cells subsets, the importance of the role they play during acute and chronic infections, and the mechanisms behind their effectiveness and persistence.

  18. Septicemia following rotavirus gastroenteritis.

    Science.gov (United States)

    Scheier, Eric; Aviner, Shraga

    2013-03-01

    Rotavirus gastroenteritis is a prevalent childhood illness rarely complicated by secondary bacterial sepsis. Although there are case reports of septicemia after rotavirus infection, there are no recent reviews on this topic. To add new cases of septicemia after rotavirus to the literature, review the few cases of septicemia after rotavirus that have been reported, calculate the incidence of septicemia in children hospitalized for rotavirus gastroenteritis, and discuss the characteristics of septicemia after rotavirus infection and implications for current pediatric practice. We identified children whose illness was complicated by septicemia from among all hospitalizations at our facility for rotavirus gastroenteritis from May 1999 through May 2010. We also review the few cases reported in the English literature. We identified two cases of septicemia from among 632 hospitalizations for rotavirus gastroenteritis in this time period, for an incidence rate of 0.32%, which is comparable to other estimates in the English literature. The typical course for cases of bacterial superinfection involves a second peak of high fever; other clinical signs are variable. Septicemia after rotavirus gastroenteritis is a rare but dangerous entity. Early identification of a child developing bacterial superinfection after rotavirus, as in any case of sepsis, is of the utmost importance, as is obtaining blood cultures in a child with a rotavirus infection and a second fever spike.

  19. The Etiology and Pathogenesis of Viral Gastroenteritis.

    Science.gov (United States)

    1984-07-31

    plentiful, are somewhat contradictory (1). Local antibodies (intestinal IgA and IgG) in one report correlated with protection from and cure of rotavirus ...F.E. and Zissis, G.: Protection of infants against rotavirus diarrhea by RIT4237 attenuated bovine rotavirus strain vaccine. The Lancet 1:977-981,1984... protective role for the systemic antibody response in children. Little obvious correlation was noted between sero- conversion after administering an

  20. The Etiology and Pathogenesis of Viral Gastroenteritis.

    Science.gov (United States)

    1986-08-01

    further support for he view that immunity to Norwalk virus is not determined by serum antibody. YAnothe_ collaborative study demonstrated the localization ...study demonstrated the localization of rotavirus to the small intestine as indicated by analysis of fluid specimens obtained by string capsule; this was...vitro cultivation of this virus is inefficient. Studies reveal that mechanisms of clinical immunity to rotavirus are complex (I). It seems likely

  1. Human Papilloma Viral DNA Replicates as a Stable Episome in Cultured Epidermal Keratinocytes

    Science.gov (United States)

    Laporta, Robert F.; Taichman, Lorne B.

    1982-06-01

    Human papilloma virus (HPV) is poorly understood because systems for its growth in tissue culture have not been developed. We report here that cultured human epidermal keratinocytes could be infected with HPV from plantar warts and that the viral DNA persisted and replicated as a stable episome. There were 50-200 copies of viral DNA per cell and there was no evidence to indicate integration of viral DNA into the cellular genome. There was also no evidence to suggest that viral DNA underwent productive replication. We conclude that cultured human epidermal keratinocytes may be a model for the study of certain aspects of HPV biology.

  2. Did viral disease of humans wipe out the Neandertals?

    Science.gov (United States)

    Wolff, Horst; Greenwood, Alex D

    2010-07-01

    Neandertals were an anatomically distinct hominoid species inhabiting a vast geographical area ranging from Portugal to western Siberia and from northern Europe to the Middle East. The species became extinct 28,000 years ago, coinciding with the arrival of anatomically modern humans (AMHs) in Europe 40,000 years ago. There has been considerable debate surrounding the main causes of the extinction of Neandertals. After at least 200,000 years of successful adaption to the climate, flora and fauna of Eurasia, it is not clear why they suddenly failed to survive. For many years, climate change or competition with anatomically modern human (AMH) have been the leading hypotheses. Recently these hypotheses have somewhat fallen out of favour due to the recognition that Neandertals were a highly developed species with complex social structure, culture and technical skills. Were AMHs lucky and survived some catastrophe that eradicated the Neandertals? It seems unlikely that this is the case considering the close timing of the arrival of AMHs and the disappearance of Neandertals. Perhaps the arrival of AMHs also brought additional new non-human microscopic inhabitants to the regions where Neandertals lived and these new inhabitants contributed to the disappearance of the species. We introduce a medical hypothesis that complements other recent explanations for the extinction of Neandertals. After the ancestors of Neandertals left Africa, their immune system adapted gradually to the pathogens in their new Eurasian environment. In contrast, AMHs continued to co-evolve with east African pathogens. More than 200,000 years later, AMHs carried pathogens that would have been alien to pre-historic Europe. First contact between long separated populations can be devastating. Recent European and American history provides evidence for similar events, where introduction of viral, protozoan or bacterial pathogens to immunologically naïve populations lead to mass mortality and local

  3. Recombinant Glycoprotein Vaccines for Human Immunodeficiency Virus-Infected Children and Their Effects on Viral Quasispecies

    OpenAIRE

    Essajee, Shaffiq M; Yogev, Ram; Pollack, Henry; Greenhouse, Bryan; Krasinski, Keith; Borkowsky, William

    2002-01-01

    In individuals infected with human immunodeficiency virus type 1 (HIV-1), specific immunity is associated with a more diverse viral repertoire and slower disease progression. Attempts to enhance antiviral immunity with therapeutic vaccination have shown that recombinant glycoprotein (RGP) vaccines are safe, well tolerated, and immunogenic, but the effect of RGP vaccines on the viral repertoire is unknown. We evaluated diversification of the viral envelope in 12 HIV-infected children who recei...

  4. Aichi virus IgG seroprevalence in Tunisia parallels genomic detection and clinical presentation in children with gastroenteritis.

    Science.gov (United States)

    Sdiri-Loulizi, Khira; Hassine, Mouna; Bour, Jean-Baptiste; Ambert-Balay, Katia; Mastouri, Maha; Aho, Ludwig-Serge; Gharbi-Khelifi, Hakima; Aouni, Zaidoun; Sakly, Nabil; Chouchane, Slaheddine; Neji-Guédiche, Mohamed; Pothier, Pierre; Aouni, Mahjoub

    2010-07-01

    Aichi virus has been described as a novel causative agent of gastroenteritis in humans. In this study, we report the seroprevalence distribution of Aichi virus in Tunisia. A panel of 1,000 sera was screened by applying an enzyme-linked immunosorbent assay for immunoglobulin G specific for Aichi virus. A considerable prevalence (92%) of antibody to Aichi virus was found across all age groups. The specific anti-Aichi virus antibodies increased with age, from a high rate (68.8%) in children under 10 years old to about 100% in persons more than 60 years old. We found a statistically significant increase in levels of antibody to Aichi virus according to the age of patients. Immunoglobulin M antibodies were detected among five children. A high frequency of Aichi virus monoinfections in hospitalized children with severe gastroenteritis was previously observed in Tunisia. Aichi virus causes diarrhea with dehydration, fever, and vomiting. This work is the first to establish a correlation between the high seroprevalence of specific Aichi virus antibodies, clinical presentation, and a high frequency of isolation of Aichi virus by genomic characterization in stools of children suffering from gastroenteritis. Our data show the importance and emerging character of Aichi virus in the viral etiology of pediatric gastroenteritis.

  5. Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation

    Directory of Open Access Journals (Sweden)

    Christel Chehoud

    2016-03-01

    Full Text Available Fecal microbiota transplantation (FMT is a highly effective treatment for refractory Clostridium difficile infections. However, concerns persist about unwanted cotransfer of pathogenic microbes such as viruses. Here we studed FMT from a single healthy human donor to three pediatric ulcerative colitis patients, each of whom received a course of 22 to 30 FMT treatments. Viral particles were purified from donor and recipient stool samples and sequenced; the reads were then assembled into contigs corresponding to viral genomes or partial genomes. Transfer of selected viruses was confirmed by quantitative PCR. Viral contigs present in the donor could be readily detected in recipients, with up to 32 different donor viral contigs appearing in a recipient sample. Reassuringly, none of these were viruses are known to replicate on human cells. Instead, viral contigs either scored as bacteriophage or could not be attributed taxonomically, suggestive of unstudied phage. The two most frequently transferred gene types were associated with temperate-phage replication. In addition, members of Siphoviridae, the group of typically temperate phages that includes phage lambda, were found to be transferred with significantly greater efficiency than other groups. On the basis of these findings, we propose that the temperate-phage replication style may promote efficient phage transfer between human individuals. In summary, we documented transfer of multiple viral lineages between human individuals through FMT, but in this case series, none were from viral groups known to infect human cells.

  6. [Etiological aspects of acute gastroenteritis--a ten-year review (1.01. 2001-31.12.2010)].

    Science.gov (United States)

    Luca, Cătălina Mihaela; Nemescu, Roxana; Teodor, Andra; Fântânaru, Rodica; Petrovici, Cristina Mirela; Dorobăţ, Carmen

    2011-01-01

    Acute gastroentritis is one of the most common diseases in humans, and continues to be a significant cause of morbidity worldwide. To determine the bacterial pathogens associated with gastroenteritis in patients admitted to the Iasi Infectious Diseases Hospital in the last ten years. A total of 40481 stool samples were examined using conventional methods. Bacteria were found in 7.36% of cases, and parasites in 9.64%; 83% of the cases were viral, micotic, or disbiotic. The bacterial etiology was dominated by Salmonella spp. (58.34%), Shigella spp. (27.08%), Yersinia enterocolitica 03 (8.53%), Campylobacter spp. (1.31%), other bacterial pathogens (EPEC, Aeromonas hydrophilla/caviae/sobria, Plesiomonas shigelloides, Bacillus cereus, Staphylococcus aureus, etc) being detected in 3.74% of the cases. Of the Salmonella species, group B (51.99%) followed by group D (45.23%) were most common. Shigella sonnei and Shigella flexneri were found in almost the same proportion (49.45% and 49.70%, respectively); Shigella boydii was isolated in only 0.85% of cases. The trend of gastroenteritis caused by bacterial pathogens is decreasing: from 355 cases in 2001 to 105 cases in 2010; three peaks have been recorded in 2002, 2005 (when Salmonella typhi was isolated in a patient), and 2008 (469, 409, and 252 cases, respectively). Bacterial gastroenteritis affected both sexes almost equally (122 males and 118 females). The most affected age groups were: 0 - 4 years, 15 - 24 years, 5 - 14 years and 25 - 39 years. Laboratory investigations are essential in determining the etiology of gastroenteritis. Its unpredictable incidence justifies the human and material efforts aimed at controlling the spread of potentially epidemic acute gastroenteritis.

  7. Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease

    Science.gov (United States)

    Butel, J. S.

    2000-01-01

    The RNA and DNA tumor viruses have made fundamental contributions to two major areas of cancer research. Viruses were vital, first, to the discovery and analysis of cellular growth control pathways and the synthesis of current concepts of cancer biology and, second, to the recognition of the etiology of some human cancers. Transforming retroviruses carry oncogenes derived from cellular genes that are involved in mitogenic signalling and growth control. DNA tumor viruses encode oncogenes of viral origin that are essential for viral replication and cell transformation; viral oncoproteins complex with cellular proteins to stimulate cell cycle progression and led to the discovery of tumor suppressors. Viral systems support the concept that cancer development occurs by the accumulation of multiple cooperating events. Viruses are now accepted as bona fide etiologic factors of human cancer; these include hepatitis B virus, Epstein-Barr virus, human papillomaviruses, human T-cell leukemia virus type I and hepatitis C virus, plus several candidate human cancer viruses. It is estimated that 15% of all human tumors worldwide are caused by viruses. The infectious nature of viruses distinguishes them from all other cancer-causing factors; tumor viruses establish long-term persistent infections in humans, with cancer an accidental side effect of viral replication strategies. Viruses are usually not complete carcinogens, and the known human cancer viruses display different roles in transformation. Many years may pass between initial infection and tumor appearance and most infected individuals do not develop cancer, although immunocompromised individuals are at elevated risk of viral-associated cancers. Variable factors that influence viral carcinogenesis are reviewed, including possible synergy between viruses and environmental cofactors. The difficulties in establishing an etiologic role for a virus in human cancer are discussed, as well as the different approaches that proved

  8. Gastro-enteritis in huisartsenpeilstations.

    NARCIS (Netherlands)

    Wit, M.A.S. de; Koopmans, M.P.G.; Kortbeek, L.M.; Leeuwen, W.J. van; Vinje, J.; Bartelds, A.I.M.; Duijnhoven, Y.T.P.H. van

    1998-01-01

    De incidentie van huisartsconsulten voor gastro-enteritis van 77 per 10.000 persoonjaren lijkt een lichte daling te vertonen t.o.v. de incidentie van 90 per 10.000 persoonjaren in een vergelijkbaar onderzoek in 1992-1993. De belangrijkste verwekkers van gastro-enteritis waarvoor de huisarts wordt

  9. Proton pump inhibitors and gastroenteritis

    NARCIS (Netherlands)

    R.J. Hassing (Robert); A. Verbon (Annelies); H. de Visser (Herman); A. Hofman (Albert); B.H.Ch. Stricker (Bruno)

    2016-01-01

    textabstractAn association between proton pump inhibitor (PPI) therapy and bacterial gastroenteritis has been suggested as well as contradicted. The aim of this study was to examine the association between the use of PPIs and occurrence of bacterial gastroenteritis in the prospective Rotterdam

  10. THE KEY VIRAL PLAYERS

    Science.gov (United States)

    A number of different types of human enteric viruses cause waterborne outbreaks when individuals are exposed to contaminated drinking and recreational waters. Members of the enterovirus group cause numerous diseases, including gastroenteritis, encephalitis, meningitis, myocard...

  11. Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine.

    Science.gov (United States)

    Cheuvart, Brigitte; Neuzil, Kathleen M; Steele, A Duncan; Cunliffe, Nigel; Madhi, Shabir A; Karkada, Naveen; Han, Htay Htay; Vinals, Carla

    2014-01-01

    Clinical trials of the human rotavirus vaccine Rotarix™ (RV1) have demonstrated significant reductions in severe rotavirus gastroenteritis (RVGE) in children worldwide. However, no correlate of vaccine efficacy (VE) has yet been established. This paper presents 2 analyses which aimed to investigate whether serum anti-RV IgA measured by ELISA 1 or 2 mo post-vaccination can serve as a correlate of efficacy against RVGE: (1) In a large Phase III efficacy trial (Rota-037), the Prentice criteria for surrogate endpoints was applied to anti-RV IgA seropositivity 1 mo post-vaccination. These criteria determine whether a significant vaccine group effect can be predicted from the surrogate, namely seropositivity (anti-RV IgA concentration>20 U/mL); (2) Among other GSK-sponsored RV1 VE studies, 8 studies which assessed immunogenicity at 1 or 2 mo post-vaccination in all or a sub-cohort of enrolled subjects and had at least 10 RVGE episodes were included in a meta-analysis to measure the regression between clinical VE and VE predicted from immunogenicity (VE1). In Rota-037, anti-RV IgA seropositivity post-vaccination was associated with a lower incidence of any or severe RVGE, however, the proportion of vaccine group effect explained by seropositivity was only 43.6% and 32.7% respectively. This low proportion was due to the vaccine group effect observed in seronegative subjects. In the meta-analysis, the slope of the regression between clinical VE and VE1 was statistically significant. These two independent analyses support the hypothesis that post-vaccination anti-RV IgA seropositivity (antibody concentration ≥20 U/mL) may serve as a useful correlate of efficacy in clinical trials of RV1 vaccines.

  12. Complete Nucleotide Sequence and Genetic Organization of Aichi Virus, a Distinct Member of the Picornaviridae Associated with Acute Gastroenteritis in Humans

    Science.gov (United States)

    Yamashita, Teruo; Sakae, Kenji; Tsuzuki, Hideaki; Suzuki, Yasumoto; Ishikawa, Naohisa; Takeda, Naokazu; Miyamura, Tatsuo; Yamazaki, Shudo

    1998-01-01

    The complete nucleotide sequence of a novel enteric virus, Aichi virus, associated with nonbacterial acute gastroenteritis in humans was determined. The Aichi virus genome proved to be a single-stranded positive-sense RNA molecule with 8,251 bases excluding a poly(A) tail; it contains a large open reading frame with 7,302 nucleotides that encodes a potential polyprotein precursor of 2,433 amino acids. The genome contains a 5′ nontranslated region (NTR) with 712 bases and a 3′ NTR with 240 bases followed by a poly(A) tail. The structure of the genome, VPg–5′ NTR–leader protein–structural proteins–nonstructural proteins–3′ NTR–poly(A), was found to be typical of a picornavirus. The VP0-VP3 and VP3-VP1 cleavage sites were determined to be Q-H and Q-T, respectively, by N-terminal amino acid sequence analyses using purified virion proteins. Possible cleavage sites, Q-G, Q-A, and Q-S, which cleave P2 and P3 polyproteins were found to be similar to those of picornaviruses. A dendrogram based on 3Dpol proteins indicated that Aichi virus is genetically distinct from the known six genera of picornaviruses including entero-, rhino-, cardio-, aphtho-, and hepatovirus and echovirus 22. Considering this together with other properties of the virus (T. Yamashita, S. Kobayashi, K. Sakae, S. Nakata, S. Chiba, Y. Ishihara, and S. Isomura, J. Infect. Dis. 164:954–957, 1991), we propose that Aichi virus be regarded as a new genus of the family Picornaviridae. PMID:9733894

  13. Human metapneumovirus viral load is an important risk factor for disease severity in young children.

    Science.gov (United States)

    Roussy, Jean-François; Carbonneau, Julie; Ouakki, Manale; Papenburg, Jesse; Hamelin, Marie-Ève; De Serres, Gaston; Boivin, Guy

    2014-06-01

    The role of viral load in human metapneumovirus (HMPV) disease severity has not yet been clearly determined. We evaluated the importance of viral load along with other factors in HMPV disease severity among children aged <3 years old. HMPV-positive cases were selected from a cohort of outpatients and hospitalized children with lower respiratory tract infections. HMPV groups (A or B) and viral loads were determined in their nasopharyngeal aspirates. Disease severity was defined by assessing risk for hospitalization and by using two validated clinical severity scores. Of the 118 HMPV cases detected over 4 years for which viral load could be determined, 60 belonged to genotype A and 58 to genotype B. Baseline characteristics were similar in HMPV-A and HMPV-B mono-infected patients. In multivariate analysis, HMPV hospitalization was associated with viral load ≥1000 copies/10(4)cells (OR, 3.2; 95%CI, 1.4-7.4), age <6 months (OR, 3.1; 95%CI, 1.2-8.6) and presence of ≥3 children in the household (OR, 2.7; 95%CI, 1.04-6.9). A high HMPV viral load was also associated with pulmonary rales (p=.03), use of bronchodilators (p=.02) and inhaled corticosteroids (p=.01). HMPV viral load is associated with disease severity in young children along with young age and household crowding. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. No association between HPV positive breast cancer and expression of human papilloma viral transcripts.

    Science.gov (United States)

    Gannon, Orla M; Antonsson, Annika; Milevskiy, Michael; Brown, Melissa A; Saunders, Nicholas A; Bennett, Ian C

    2015-12-14

    Infectious agents are thought to be responsible for approximately 16% of cancers worldwide, however there are mixed reports in the literature as to the prevalence and potential pathogenicity of viruses in breast cancer. Furthermore, most studies to date have focused primarily on viral DNA rather than the expression of viral transcripts. We screened a large cohort of fresh frozen breast cancer and normal breast tissue specimens collected from patients in Australia for the presence of human papilloma virus (HPV) DNA, with an overall prevalence of HPV of 16% and 10% in malignant and non-malignant tissue respectively. Samples that were positive for HPV DNA by nested PCR were screened by RNA-sequencing for the presence of transcripts of viral origin, using three different bioinformatic pipelines. We did not find any evidence for HPV or other viral transcripts in HPV DNA positive samples. In addition, we also screened publicly available breast RNA-seq data sets for the presence of viral transcripts and did not find any evidence for the expression of viral transcripts (HPV or otherwise) in other data sets. This data suggests that transcription of viral genomes is unlikely to be a significant factor in breast cancer pathogenesis.

  15. Trehalose-mediated autophagy impairs the anti-viral function of human primary airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Qun Wu

    Full Text Available Human rhinovirus (HRV is the most common cause of acute exacerbations of chronic lung diseases including asthma. Impaired anti-viral IFN-λ1 production and increased HRV replication in human asthmatic airway epithelial cells may be one of the underlying mechanisms leading to asthma exacerbations. Increased autophagy has been shown in asthmatic airway epithelium, but the role of autophagy in anti-HRV response remains uncertain. Trehalose, a natural glucose disaccharide, has been recognized as an effective autophagy inducer in mammalian cells. In the current study, we used trehalose to induce autophagy in normal human primary airway epithelial cells in order to determine if autophagy directly regulates the anti-viral response against HRV. We found that trehalose-induced autophagy significantly impaired IFN-λ1 expression and increased HRV-16 load. Inhibition of autophagy via knockdown of autophagy-related gene 5 (ATG5 effectively rescued the impaired IFN-λ1 expression by trehalose and subsequently reduced HRV-16 load. Mechanistically, ATG5 protein interacted with retinoic acid-inducible gene I (RIG-I and IFN-β promoter stimulator 1 (IPS-1, two critical molecules involved in the expression of anti-viral interferons. Our results suggest that induction of autophagy in human primary airway epithelial cells inhibits the anti-viral IFN-λ1 expression and facilitates HRV infection. Intervention of excessive autophagy in chronic lung diseases may provide a novel approach to attenuate viral infections and associated disease exacerbations.

  16. Viral Metagenomics on Animals as a Tool for the Detection of Zoonoses Prior to Human Infection?

    Science.gov (United States)

    Temmam, Sarah; Davoust, Bernard; Berenger, Jean-Michel; Raoult, Didier; Desnues, Christelle

    2014-01-01

    Many human viral infections have a zoonotic, i.e., wild or domestic animal, origin. Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and replicate in its new human host, human-to-human transmissions may occur, possibly resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus, predicting emerging zoonotic infections is an important challenge for public health officials in the coming decades. The recent development of viral metagenomics, i.e., the characterization of the complete viral diversity isolated from an organism or an environment using high-throughput sequencing technologies, is promising for the surveillance of such diseases and can be accomplished by analyzing the viromes of selected animals and arthropods that are closely in contact with humans. In this review, we summarize our current knowledge of viral diversity within such animals (in particular blood-feeding arthropods, wildlife and domestic animals) using metagenomics and present its possible future application for the surveillance of zoonotic and arboviral diseases. PMID:24918293

  17. Viral symbiosis and the holobiontic nature of the human genome.

    Science.gov (United States)

    Ryan, Francis Patrick

    2016-01-01

    The human genome is a holobiontic union of the mammalian nuclear genome, the mitochondrial genome and large numbers of endogenized retroviral genomes. This article defines and explores this symbiogenetic pattern of evolution, looking at the implications for human genetics, epigenetics, embryogenesis, physiology and the pathogenesis of inborn errors of metabolism and many other diseases. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  18. Ultra-Sensitive HIV-1 Latency Viral Outgrowth Assays Using Humanized Mice

    Directory of Open Access Journals (Sweden)

    Kimberly Schmitt

    2018-03-01

    Full Text Available In the current quest for a complete cure for HIV/AIDS, highly sensitive HIV-1 latency detection methods are critical to verify full viral eradication. Until now, the in vitro quantitative viral outgrowth assays (qVOA have been the gold standard for assessing latent HIV-1 viral burden. However, these assays have been inadequate in detecting the presence of ultralow levels of latent virus in a number of patients who were initially thought to have been cured, but eventually showed viral rebound. In this context, new approaches utilizing in vivo mouse-based VOAs are promising. In the murine VOA (mVOA, large numbers of CD4+ T cells or PBMC from aviremic subjects are xenografted into immunodeficient NSG mice, whereas in the humanized mouse-based VOA (hmVOA patient CD4+ T cell samples are injected into BLT or hu-hematopoetic stem cells (hu-HSC humanized mice. While latent virus could be recovered in both of these systems, the hmVOA provides higher sensitivity than the mVOA using a fewer number of input cells. In contrast to the mVOA, the hmVOA provides a broader spectrum of highly susceptible HIV-1 target cells and enables newly engrafted cells to home into preformed human lymphoid organs where they can infect cells in situ after viral activation. Hu-mice also allow for both xenograft- and allograft-driven cell expansions with less severe GvH providing a longer time frame for potential viral outgrowth from cells with a delayed latent viral activation. Based on these advantages, the hmVOA has great potential in playing an important role in HIV-1 latency and cure research.

  19. Partner Human Papillomavirus Viral Load and Incident Human Papillomavirus Detection in Heterosexual Couples.

    Science.gov (United States)

    Grabowski, Mary K; Kong, Xiangrong; Gray, Ronald H; Serwadda, David; Kigozi, Godfrey; Gravitt, Patti E; Nalugoda, Fred; Reynolds, Steven J; Wawer, Maria J; Redd, Andrew D; Watya, Stephen; Quinn, Thomas C; Tobian, Aaron A R

    2016-03-15

    The association between partner human papillomavirus (HPV) viral load and incident HPV detection in heterosexual couples is unknown. HPV genotypes were detected in 632 human immunodeficiency virus (HIV)-negative couples followed for 2 years in a male circumcision trial in Rakai, Uganda, using the Roche HPV Linear Array. This assay detects 37 genotypes and provides a semiquantitative measure of viral load based on the intensity (graded 1-4) of the genotype-specific band; a band intensity of 1 indicates a low genotype-specific HPV load, whereas an intensity of 4 indicates a high load. Using Poisson regression with generalized estimating equations, we measured the association between partner's genotype-specific viral load and detection of that genotype in the HPV-discordant partner 1 year later. Incident detection of HPV genotypes was 10.6% among men (54 of 508 genotype-specific visit intervals) and 9.0% among women (55 of 611 genotype-specific visit intervals). Use of male partners with a baseline genotype-specific band intensity of 1 as a reference yielded adjusted relative risks (aRRs) of 1.14 (95% confidence interval [CI], .58-2.27]) for incident detection of that genotype among women whose male partner had a baseline band intensity of 2, 1.75 (95% CI, .97-3.17) among those whose partner had an intensity of 3, and 2.52 (95% CI, 1.40-4.54) among those whose partner had an intensity of 4. Use of female partners with a baseline genotype-specific band intensity of 1 as a reference yielded an aRR of 2.83 (95% CI, 1.50-5.33) for incident detection of that genotype among men whose female partner had a baseline band intensity of 4. These associations were similar for high-risk and low-risk genotypes. Male circumcision also was associated with significant reductions in incident HPV detection in men (aRR, 0.53 [95% CI, .30-.95]) and women (aRR, 0.42 [95% CI, .23-.76]). In heterosexual couples, the genotype-specific HPV load in one partner is associated with the risk of new

  20. Coupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes

    Directory of Open Access Journals (Sweden)

    Dresang Lindsay R

    2011-12-01

    Full Text Available Abstract Background Kaposi's sarcoma-associated herpesvirus (KSHV and Epstein-Barr virus (EBV are related human tumor viruses that cause primary effusion lymphomas (PEL and Burkitt's lymphomas (BL, respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. Results The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. Conclusions This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.

  1. Coupled Transcriptome and Proteome Analysis of Human Lymphotropic Tumor Viruses: Insights on the Detection and Discovery of Viral Genes

    Energy Technology Data Exchange (ETDEWEB)

    Dresang, Lindsay R.; Teuton, Jeremy R.; Feng, Huichen; Jacobs, Jon M.; Camp, David G.; Purvine, Samuel O.; Gritsenko, Marina A.; Li, Zhihua; Smith, Richard D.; Sugden, Bill; Moore, Patrick S.; Chang, Yuan

    2011-12-20

    Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. Results The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. Conclusions This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.

  2. Understanding "Human" Waves: Exploiting the Physics in a Viral Video

    Science.gov (United States)

    Ferrer-Roca, Chantal

    2018-01-01

    Waves are a relevant part of physics that students find difficult to grasp, even in those cases in which wave propagation kinematics can be visualized. This may hinder a proper understanding of sound, light or quantum physics phenomena that are explained using a wave model. So-called "human" waves, choreographed by people, have proved to…

  3. Human parechoviruses as an important viral cause of sepsislike illness and meningitis in young children

    NARCIS (Netherlands)

    Wolthers, Katja C.; Benschop, Kimberley S. M.; Schinkel, Janke; Molenkamp, Richard; Bergevoet, Rosemarijn M.; Spijkerman, Ingrid J. B.; Kraakman, H. Carlijn; Pajkrt, Dasja

    2008-01-01

    BACKGROUND: Enteroviruses (EVs) belong to the family Picornaviridae and are a well-known cause of neonatal sepsis and viral meningitis. Human parechoviruses (HPeVs) type 1 and 2, previously named echovirus 22 and 23, have been associated with mild gastrointestinal or respiratory symptoms in young

  4. VIRUS OF HUMAN PAPILLOMA. EPIDEMIOLOGY, LABORATORY DIAGNOSTICS AND PREVENTION OF PAPILLOMA VIRAL INFECTION

    Directory of Open Access Journals (Sweden)

    O. V. Narvskaya

    2011-01-01

    Full Text Available Abstract. The information reflected modern knowledge about virus of human papilloma (VHP and pathogenesis of papilloma viral infection is presented in the lecture. The actual problems of epidemiology, laboratory diagnostics and prevention of VHP associated damage of cervical epithelium have been described.

  5. Using experimental human influenza infections to validate a viral dynamic model and the implications for prediction.

    Science.gov (United States)

    Chen, S C; You, S H; Liu, C Y; Chio, C P; Liao, C M

    2012-09-01

    The aim of this work was to use experimental infection data of human influenza to assess a simple viral dynamics model in epithelial cells and better understand the underlying complex factors governing the infection process. The developed study model expands on previous reports of a target cell-limited model with delayed virus production. Data from 10 published experimental infection studies of human influenza was used to validate the model. Our results elucidate, mechanistically, the associations between epithelial cells, human immune responses, and viral titres and were supported by the experimental infection data. We report that the maximum total number of free virions following infection is 10(3)-fold higher than the initial introduced titre. Our results indicated that the infection rates of unprotected epithelial cells probably play an important role in affecting viral dynamics. By simulating an advanced model of viral dynamics and applying it to experimental infection data of human influenza, we obtained important estimates of the infection rate. This work provides epidemiologically meaningful results, meriting further efforts to understand the causes and consequences of influenza A infection.

  6. Gag sequence variation in a human immunodeficiency virus type 1 transmission cluster influences viral replication fitness

    NARCIS (Netherlands)

    Gijsbers, Esther F.; van Nuenen, Ad C.; Schuitemaker, Hanneke; Kootstra, Neeltje A.

    2013-01-01

    Three men from a proven homosexual human immunodeficiency virus type 1 (HIV-1) transmission cluster showed large variation in their clinical course of infection. To evaluate the effect of evolution of the same viral variant in these three patients, we analysed sequence variation in the capsid

  7. Convulsion following gastroenteritis in children without severe electrolyte imbalance.

    Science.gov (United States)

    Ghorashi, Ziaaedin; Nezami, Nariman; Soltani-Ahari, Hassan; Ghorashi, Sona

    2010-01-01

    Three to five million children from among one billion with gastroenteritis die annually worldwide. The etiologic agent in developed countries is viral in 15-60% of cases, while in developing countries, bacteria and parasites are frequently reported as the etiologic factors. Neurologic signs including convulsion are seen in some cases of diarrhea. This study aimed to investigate the etiology, risk factors and short-term prognosis of gastroenteritis with convulsion. During a case-control study, 100 patients with gastroenteritis were enrolled into the case and control groups on the basis of convulsion or no convulsion development, respectively. This study was conducted in Tabriz Children's Hospital from March 2004 to March 2007. The age of patients ranged from 2 months to 7 years, and the groups were age- and sex-matched. Body temperature (BT), severity and type of dehydration, stool exam and culture, past history of convulsion in the patient and first-degree relatives, electrolyte imbalance, and short-term prognosis were studied and compared. The mean weight of groups was not different, while the frequency of fever at the time of admission, past history of febrile convulsion in first-degree relatives and severity of dehydration were significantly higher in the case group (p electrolyte imbalance was observed in patients with gastroenteritis experiencing febrile convulsion.

  8. Viral latency in blood and saliva of simian foamy virus-infected humans.

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    Rejane Rua

    Full Text Available Simian foamy viruses (SFV are widespread retroviruses among non-human primates (NHP. SFV actively replicate in the oral cavity and can be transmitted to humans through NHP bites, giving rise to a persistent infection. We aimed at studying the natural history of SFV infection in human. We have analyzed viral load and gene expression in 14 hunters from Cameroon previously shown to be infected with a gorilla SFV strain. Viral DNA could be detected by quantitative polymerase chain reaction (q-PCR targeting the pol-in region, in most samples of peripheral blood mononuclear cells (PBMCs (7.1 ± 6.0 SFV DNA copies/105 PBMCs and saliva (2.4 ± 4.3 SFV DNA copies/105 cells derived from the hunters. However, quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR revealed the absence of SFV viral gene expression in both PBMCs and saliva, suggesting that SFV was latent in the human samples. Our study demonstrates that a latent infection can occur in humans and persist for years, both in PBMCs and saliva. Such a scenario may contribute to the putative lack of secondary human-to-human transmissions of SFV.

  9. Inhibition of viral gene expression by human ribonuclease P.

    Science.gov (United States)

    Kawa, D; Wang, J; Yuan, Y; Liu, F

    1998-11-01

    External guide sequences (EGSs) are small RNA molecules which consist of a sequence complementary to a target mRNA and render the target RNA susceptible to degradation by ribonuclease P (RNase P). EGSs were designed to target the mRNA encoding thymidine kinase (TK) of herpes simplex virus 1 for degradation. These EGSs were shown to be able to direct human RNase P to cleave the TK mRNA sequence efficiently in vitro. A reduction of about 80% in the expression level of both TK mRNA and protein was observed in human cells that steadily expressed an EGS, but not in cells that either did not express the EGS or produced a "disabled" EGS which carried a single nucleotide mutation that precluded RNase P recognition. Thus, EGSs may represent novel gene-targeting agents for inhibition of gene expression and antiviral activity.

  10. Dried blood spots, valid screening for viral hepatitis and human immunodeficiency virus in real-life

    DEFF Research Database (Denmark)

    Mössner, Belinda K; Staugaard, Benjamin; Jensen, Janne

    2016-01-01

    AIM: To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS: We included prospective patients with known viral infections from drug treatment......, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%). CONCLUSION: DBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV...

  11. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

    OpenAIRE

    Levi, José E.; Fink, Maria C.S.; Canto, Cynthia L.M.; Carretiero, Nadily; Matsubara, Regina; Linhares, Iara; Dores, Gérson B. das; Castelo, Adauto; Segurado, Aluísio; Uip, David E.; Eluf Neto, José

    2002-01-01

    HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%). Twenty (7.5%) women were infected by one or more low-risk viruses, 89 (33%...

  12. Use of an improved quantitative polymerase chain reaction assay to determine differences in human rhinovirus viral loads in different populations.

    Science.gov (United States)

    Granados, Andrea; Luinstra, Kathy; Chong, Sylvia; Goodall, Emma; Banh, Lisa; Mubareka, Samira; Smieja, Marek; Mahony, James

    2012-12-01

    Human rhinoviruses (HRV) frequently cause acute respiratory infections and chronic respiratory disease exacerbations. However, testing is not generally offered. We developed a modified HRV quantitative polymerase chain reaction (qPCR) assay to assess viral loads in the community and hospital patients. The assay had a lower limit of detection of 2 log(10) viral copies/mL and displayed linearity over 5 log(10) viral copies, with a lower limit of quantitation of 4 log(10) viral copies/mL. Mean viral loads (95% confidence interval) for hospitalized children, university students, and institutionalized elderly, were 7.08 log(10) viral copies/mL (6.7-7.5), 6.87 log(10) viral copies/mL (6.5-7.2), and 7.09 log(10) viral copies/mL (6.9-7.3), respectively (P = 0.67). Serial specimens of 14 university students showed a decrease of mean viral loads from 6.36 log(10) viral copies/mL on day 1 to 2.32 log(10) viral copies/mL 7 days past symptom onset (P < 0.001). Using an HRV qPCR, we showed that viral loads did not differ between the community and hospitalized populations and significantly decreased following symptoms onset in healthy individuals. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Viral Etiology Relationship between Human Papillomavirus and Human Breast Cancer and Target of Gene Therapy.

    Science.gov (United States)

    Yan, Chen; Teng, Zhi Ping; Chen, Yun Xin; Shen, Dan Hua; Li, Jin Tao; Zeng, Yi

    2016-05-01

    To explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer. PCR was used to screen HPV16 and HPV18 oncogenes E6 and E7 in the SKBR3 cell line and in 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18 E6 and E7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined. HPV18 oncogenes E6 and E7 were amplified and sequenced from the SKBR3 cells. Of the patient samples, 6.58% and 23.68% were tested to be positive for HPV18 E6 and HPV18 E7. In the cell culture models, the knockdown of HPV18 E6 and E7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins. HPV was a contributor to virus caused human breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  14. 1st International Symposium on Stress-Associated RNA Granules in Human Disease and Viral Infection

    Directory of Open Access Journals (Sweden)

    Bruce W. Banfield

    2014-09-01

    Full Text Available In recent years, important linkages have been made between RNA granules and human disease processes. On June 8-10 of this year, we hosted a new symposium, dubbed the 1st International Symposium on Stress-Associated RNA Granules in Human Disease and Viral Infection. This symposium brought together experts from diverse research disciplines ranging from cancer and neuroscience to infectious disease. This report summarizes speaker presentations and highlights current challenges in the field.

  15. Inhibition of viral gene expression by human ribonuclease P.

    OpenAIRE

    Kawa, D; Wang, J; Yuan, Y.; Liu, F

    1998-01-01

    External guide sequences (EGSs) are small RNA molecules which consist of a sequence complementary to a target mRNA and render the target RNA susceptible to degradation by ribonuclease P (RNase P). EGSs were designed to target the mRNA encoding thymidine kinase (TK) of herpes simplex virus 1 for degradation. These EGSs were shown to be able to direct human RNase P to cleave the TK mRNA sequence efficiently in vitro. A reduction of about 80% in the expression level of both TK mRNA and protein w...

  16. Application of a Reverse Transcription-PCR for Identification and Differentiation of Aichi Virus, a New Member of the Picornavirus Family Associated with Gastroenteritis in Humans

    Science.gov (United States)

    Yamashita, T.; Sugiyama, M.; Tsuzuki, H.; Sakae, K.; Suzuki, Y.; Miyazaki, Y.

    2000-01-01

    Aichi viruses isolated in Vero cells from seven patients in five gastroenteritis outbreaks in Japan, five Japanese returning from Southeast Asian countries, and five local children in Pakistan with gastroenteritis were examined for differentiation based on their reactivities with a monoclonal antibody to a standard strain (A846/88) and a reverse transcription-PCR (RT-PCR) of three genomic regions. The RNA sequences were determined for 519 bases of these 17 isolates at the putative junction between the C terminus of 3C and the N terminus of 3D. The analyses revealed an approximately 90% homology between these isolates, which were then divided into two groups: group 1 (genotype A) included six isolates from four outbreaks and one isolate from a traveler and group 2 (genotype B) included one isolate from the other outbreak, four isolates from returning travelers, and all of the isolates from the Pakistani children. Based on the isolate sequences, a primer pair and a biotin-labeled probe were designed for amplification and detection of 223 bases at the 3C-3D junction of Aichi virus RNA in fecal specimens. The Aichi virus RNA was detected in 54 (55%) of 99 fecal specimens from the patients in 12 (32%) of 37 outbreaks of gastroenteritis in Japan. Of the 12 outbreaks, 11 were suspected to be due to genotype A. These results indicated that RT-PCR can be a useful tool to detect Aichi virus in stool samples and that a sequence analysis of PCR products can be employed to identify the prevalent strain in each incident. PMID:10921958

  17. Human parechoviruses as an important viral cause of sepsislike illness and meningitis in young children.

    Science.gov (United States)

    Wolthers, Katja C; Benschop, Kimberley S M; Schinkel, Janke; Molenkamp, Richard; Bergevoet, Rosemarijn M; Spijkerman, Ingrid J B; Kraakman, H Carlijn; Pajkrt, Dasja

    2008-08-01

    Enteroviruses (EVs) belong to the family Picornaviridae and are a well-known cause of neonatal sepsis and viral meningitis. Human parechoviruses (HPeVs) type 1 and 2, previously named echovirus 22 and 23, have been associated with mild gastrointestinal or respiratory symptoms in young children. Six HPeV genotypes are currently known, of which HPeV3 is associated with neonatal sepsis and meningitis. Cerebrospinal fluid samples from children aged meningitis, which led to hospitalization and antibiotic treatment. EV-specific PCRs do not detect HPeVs. The addition of an HPeV-specific PCR has led to a 31% increase in detection of a viral cause of neonatal sepsis or central nervous system symptoms in children aged viral sepsis and meningitis in young children, and rapid identification of HPeV by PCR could contribute to shorter duration of both antibiotic use and hospital stay.

  18. Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.

    Science.gov (United States)

    Zou, Wei; Wang, Zekun; Xiong, Min; Chen, Aaron Yun; Xu, Peng; Ganaie, Safder S; Badawi, Yomna; Kleiboeker, Steve; Nishimune, Hiroshi; Ye, Shui Qing; Qiu, Jianming

    2017-12-13

    Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this study provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication.IMPORTANCE Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red-cell aplasia. In fetuses, B19V infection can result in non-immune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression, and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly

  19. When the human viral infectome and diseasome networks collide: towards a systems biology platform for the aetiology of human diseases

    Directory of Open Access Journals (Sweden)

    de Chassey Benoit

    2011-01-01

    Full Text Available Abstract Background Comprehensive understanding of molecular mechanisms underlying viral infection is a major challenge towards the discovery of new antiviral drugs and susceptibility factors of human diseases. New advances in the field are expected from systems-level modelling and integration of the incessant torrent of high-throughput "-omics" data. Results Here, we describe the Human Infectome protein interaction Network, a novel systems virology model of a virtual virus-infected human cell concerning 110 viruses. This in silico model was applied to comprehensively explore the molecular relationships between viruses and their associated diseases. This was done by merging virus-host and host-host physical protein-protein interactomes with the set of genes essential for viral replication and involved in human genetic diseases. This systems-level approach provides strong evidence that viral proteomes target a wide range of functional and inter-connected modules of proteins as well as highly central and bridging proteins within the human interactome. The high centrality of targeted proteins was correlated to their essentiality for viruses' lifecycle, using functional genomic RNAi data. A stealth-attack of viruses on proteins bridging cellular functions was demonstrated by simulation of cellular network perturbations, a property that could be essential in the molecular aetiology of some human diseases. Networking the Human Infectome and Diseasome unravels the connectivity of viruses to a wide range of diseases and profiled molecular basis of Hepatitis C Virus-induced diseases as well as 38 new candidate genetic predisposition factors involved in type 1 diabetes mellitus. Conclusions The Human Infectome and Diseasome Networks described here provide a unique gateway towards the comprehensive modelling and analysis of the systems level properties associated to viral infection as well as candidate genes potentially involved in the molecular aetiology

  20. When the human viral infectome and diseasome networks collide: towards a systems biology platform for the aetiology of human diseases.

    Science.gov (United States)

    Navratil, Vincent; de Chassey, Benoit; Combe, Chantal Rabourdin; Lotteau, Vincent

    2011-01-21

    Comprehensive understanding of molecular mechanisms underlying viral infection is a major challenge towards the discovery of new antiviral drugs and susceptibility factors of human diseases. New advances in the field are expected from systems-level modelling and integration of the incessant torrent of high-throughput "-omics" data. Here, we describe the Human Infectome protein interaction Network, a novel systems virology model of a virtual virus-infected human cell concerning 110 viruses. This in silico model was applied to comprehensively explore the molecular relationships between viruses and their associated diseases. This was done by merging virus-host and host-host physical protein-protein interactomes with the set of genes essential for viral replication and involved in human genetic diseases. This systems-level approach provides strong evidence that viral proteomes target a wide range of functional and inter-connected modules of proteins as well as highly central and bridging proteins within the human interactome. The high centrality of targeted proteins was correlated to their essentiality for viruses' lifecycle, using functional genomic RNAi data. A stealth-attack of viruses on proteins bridging cellular functions was demonstrated by simulation of cellular network perturbations, a property that could be essential in the molecular aetiology of some human diseases. Networking the Human Infectome and Diseasome unravels the connectivity of viruses to a wide range of diseases and profiled molecular basis of Hepatitis C Virus-induced diseases as well as 38 new candidate genetic predisposition factors involved in type 1 diabetes mellitus. The Human Infectome and Diseasome Networks described here provide a unique gateway towards the comprehensive modelling and analysis of the systems level properties associated to viral infection as well as candidate genes potentially involved in the molecular aetiology of human diseases.

  1. Correlation analysis of high-risk human papillomavirus viral load and cervical lesions

    Directory of Open Access Journals (Sweden)

    Xiao-xing MA

    2012-05-01

    Full Text Available Objective  To explore the association between high-risk human papillomavirus (HR-HPV viral load and pathological grades of cervical intraepithelial neoplasia (CIN and cervical cancer. Methods  A total of 1248 patients from General Hospital of PLA, who underwent colposcopy and surgery due to cervical lesions between Jan. 2006 and Aug. 2011 were enrolled in this study, and they were divided five groups: cervicitis, CIN Ⅰ, CIN Ⅱ-Ⅲ, stage Ⅰ cervical cancer and stage Ⅱ cervical cancer. HR-HPV viral load (RLU/CO was determined by the Hybrid Capture Ⅱ (HCⅡ system, and they were categorized into five groups: 0-0.99, 1.00-9.99, 10.00-99.99, 100.00-999.99, ≥1000.00. The mean value and standard deviation of different HR-HPV viral load in the patients with cervicitis or with CIN Ⅰ, CINⅡ-Ⅲ, stage Ⅰ cervical cancer or stage Ⅱ cervical cancer were compared, and the correlation of HR-HPV viral load and pathogenesis of cervical lesions was analyzed. Results  HPV viral loads were significantly higher in CINⅠ(842.1±983.9, CINⅡ-Ⅲ (690.1±795.0, stage Ⅰ cervical cancer (893.1±974.2 and stage Ⅱ cervical cancer (699.5±908.3 patients than in cervicitis patients (274.2±613.6, P < 0.05, and the HPV viral loads in CINⅠ(842.1±983.9 and stage Ⅰ cervical cancer patients were higher than those in CINⅡ-Ⅲ patients (P < 0.05. When HR-HPV viral load was ≥100RLU/CO, the risk of CIN and cervical cancer increased with the increase in viral load, but there was no correlation between the viral load and pathological grades of cervical lesions. In the patients with stage ⅠB-Ⅱ cervical squamous cell carcinoma, when the HR-HPV viral load was ≥100RLU/CO, the risk of lymph node metastasis increased (P < 0.05, and the number of patients with maximum diameter of the cervical tumor ≥4cm also increased (P < 0.05. However, the HR-HPV viral load was not correlated with patient age, pathological type of the lesion, depth of cancer

  2. Development of rhabdomyolysis in a child after norovirus gastroenteritis.

    Science.gov (United States)

    Nishio, Tomohiro; Yonetani, Ryoko; Ito, Eisuke; Yoneta, Makiko; Maruo, Yoshihiro; Yoshida, Tokiko; Sugimoto, Tohru

    2016-11-04

    In children, the most significant cause of rhabdomyolysis or muscle breakdown is viral infection. However, there are no reports that norovirus, a gastroenteric virus that commonly infects children, specifically causes rhabdomyolysis. Here, we report the first pediatric case of norovirus-associated rhabdomyolysis. The patient, a 2-year-old boy with fever, diarrhea, and vomiting, was referred to our hospital with dysstasia and transaminitis. He was diagnosed with rhabdomyolysis. Additionally, norovirus genogroup GII was detected from stool samples by real-time quantitative reverse transcription Polymerase Chain Reaction, and thereafter, the norovirus GII.4 variant was identified. However, the association between rhabdomyolysis and the isolated norovirus variant was not clarified. After treatment the patient recovered without renal failure or disseminated intravascular coagulation. Rhabdomyolysis is a disease for which there is a need for early detection and treatment. If abnormal posture or muscle weakness is observed during the course of gastroenteritis, blood and urinary tests should be performed to rule out rhabdomyolysis.

  3. Glycolipid-peptide conjugate vaccines enhance CD8+ T cell responses against human viral proteins.

    Science.gov (United States)

    Speir, M; Authier-Hall, A; Brooks, C R; Farrand, K J; Compton, B J; Anderson, R J; Heiser, A; Osmond, T L; Tang, C W; Berzofsky, J A; Terabe, M; Painter, G F; Hermans, I F; Weinkove, R

    2017-10-27

    An important goal of vaccination against viruses and virus-driven cancers is to elicit cytotoxic CD8+ T cells specific for virus-derived peptides. CD8+ T cell responses can be enhanced by engaging help from natural killer T (NKT) cells. We have produced synthetic vaccines that induce strong peptide-specific CD8+ T cell responses in vivo by incorporating an NKT cell-activating glycolipid. Here we examine the effect of a glycolipid-peptide conjugate vaccine incorporating an NKT cell-activating glycolipid linked to an MHC class I-restricted peptide from a viral antigen in human peripheral blood mononuclear cells. The vaccine induces CD1d-dependent activation of human NKT cells following enzymatic cleavage, activates human dendritic cells in an NKT-cell dependent manner, and generates a pool of activated antigen-specific CD8+ T cells with cytotoxic potential. Compared to unconjugated peptide, the vaccine upregulates expression of genes encoding interferon-γ, CD137 and granzyme B. A similar vaccine incorporating a peptide from the clinically-relevant human papilloma virus (HPV) 16 E7 oncoprotein induces cytotoxicity against peptide-expressing targets in vivo, and elicits a better antitumor response in a model of E7-expressing lung cancer than its unconjugated components. Glycolipid-peptide conjugate vaccines may prove useful for the prevention or treatment of viral infections and tumors that express viral antigens.

  4. Chromosomally Integrated Human Herpesvirus 6: Models of Viral Genome Release from the Telomere and Impacts on Human Health

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    Michael L. Wood

    2017-07-01

    Full Text Available Human herpesvirus 6A and 6B, alongside some other herpesviruses, have the striking capacity to integrate into telomeres, the terminal repeated regions of chromosomes. The chromosomally integrated forms, ciHHV-6A and ciHHV-6B, are proposed to be a state of latency and it has been shown that they can both be inherited if integration occurs in the germ line. The first step in full viral reactivation must be the release of the integrated viral genome from the telomere and here we propose various models of this release involving transcription of the viral genome, replication fork collapse, and t-circle mediated release. In this review, we also discuss the relationship between ciHHV-6 and the telomere carrying the insertion, particularly how the presence and subsequent partial or complete release of the ciHHV-6 genome may affect telomere dynamics and the risk of disease.

  5. WATERBORNE OUTBREAK OF GASTROENTERITIS ASSOCIATED WITH A NOROVIRUS

    Science.gov (United States)

    The Wyoming Department of Health investigated an outbreak of acute gastroenteritis among persons who dined at a tourist saloon in central Wyoming during October 2001. Human caliciviruses (HuCVs) were suspected as the etiological agent of the outbreak based upon the incubation ...

  6. Glutathione Transferase as a Potential Marker for Gut Epithelial Injury versus the Protective Role of Breast Milk sIgA in Infants with Rota Virus Gastroenteritis

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    Lobna S. Sherif

    2015-11-01

    CONCLUSION: Breast feeding should be encouraged and highly recommended in the first two years of life as it provides Secretory IgA to breast fed infants who in turn protect them against epithelial damage caused by Rota viral gastroenteritis.

  7. Human ?-defensin-2 production upon viral and bacterial co-infection is attenuated in COPD

    OpenAIRE

    Arnason, Jason W.; Murphy, James C.; Kooi, Cora; Wiehler, Shahina; Traves, Suzanne L.; Shelfoon, Christopher; Maciejewski, Barbara; Dumonceaux, Curtis J.; Lewenza, W. Shawn; Proud, David; Leigh, Richard

    2017-01-01

    Viral-bacterial co-infections are associated with severe exacerbations of COPD. Epithelial antimicrobial peptides, including human ?-defensin-2 (HBD-2), are integral to innate host defenses. In this study, we examined how co-infection of airway epithelial cells with rhinovirus and Pseudomonas aeruginosa modulates HBD-2 expression, and whether these responses are attenuated by cigarette smoke and in epithelial cells obtained by bronchial brushings from smokers with normal lung function or from...

  8. Environmental parameters influence non-viral transfection of human mesenchymal stem cells for tissue engineering applications

    Science.gov (United States)

    King, William J.; Kouris, Nicholas A.; Choi, Siyoung; Ogle, Brenda M.; Murphy, William L.

    2012-01-01

    Non-viral transfection is a promising technique which could be used to increase the therapeutic potential of stem cells. The purpose of this study was to explore practical culture parameters of relevance in potential human mesenchymal stem cell (hMSC) clinical and tissue engineering applications, including type of polycationic transfection reagent, N/P ratio and dose of polycation/pDNA polyplexes, cell passage number, cell density, and cell proliferation. The non-viral transfection efficiency was significantly influenced by N/P ratio, polyplex dose, cell density, and cell passage number. hMSC culture conditions that inhibited cell division also decreased transfection efficiency, suggesting that strategies to promote hMSC proliferation may be useful to enhance transfection efficiency in future tissue engineering studies. Non-viral transfection treatments influenced hMSC phenotype, including the expression level of the hMSC marker CD105, and the ability of hMSCs to differentiate down the osteogenic and adipogenic lineages. The parameters found here to promote hMSC transfection efficiency, minimize toxicity, and influence hMSC phenotype may be instructive in future non-viral transfection studies and tissue engineering applications. PMID:22277991

  9. Viral characteristics of human papillomavirus infection and antioxidant levels as risk factors for cervical dysplasia.

    Science.gov (United States)

    Ho, G Y; Palan, P R; Basu, J; Romney, S L; Kadish, A S; Mikhail, M; Wassertheil-Smoller, S; Runowicz, C; Burk, R D

    1998-11-23

    Genital human papillomavirus (HPV) infection is the major causal factor of cervical intraepithelial neoplasia (CIN). The potential role of nutrition as an additional, independent risk factor for CIN has not been appropriately addressed in the context of HPV. This case-control study evaluated the etiologic role of HPV in terms of viral type and load and examined the association between CIN and plasma levels of micronutrients adjusting for HPV. Cases (n = 378) with histo-pathologically confirmed CIN and controls (n = 366) with no history of abnormal Pap smears were recruited from colposcopy and gynecology clinics, respectively. Risk of CIN was significantly increased among women who were infected with multiple HPV types (odds ratio [OR] = 21.06), a high viral load (OR = 13.08) and HPV 16 (OR = 62.49). After adjusting for HPV positivity and demographic factors, there was an inverse correlation between plasma alpha-tocopherol and risk of CIN (OR = 0.15). Plasma ascorbic acid was protective at a high level of > or = 0.803 mg/dl (OR = 0.46). CIN was not associated with plasma retinol and beta-carotene levels. The effect of genital HPV infection on CIN development is highly influenced by oncogenic viral type and high viral load. Vitamins C and E may play an independent protective role in development of CIN that needs to be confirmed in prospective studies.

  10. Systems-biology approaches to discover anti-viral effectors of the human innate immune response.

    Science.gov (United States)

    Münk, Carsten; Sommer, Andreas F R; König, Renate

    2011-07-01

    Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology "omics" methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1), Hepatitis C virus (HCV), West Nile virus (WNV), and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.

  11. Viral Metagenomics on Blood-Feeding Arthropods as a Tool for Human Disease Surveillance.

    Science.gov (United States)

    Brinkmann, Annika; Nitsche, Andreas; Kohl, Claudia

    2016-10-19

    Surveillance and monitoring of viral pathogens circulating in humans and wildlife, together with the identification of emerging infectious diseases (EIDs), are critical for the prediction of future disease outbreaks and epidemics at an early stage. It is advisable to sample a broad range of vertebrates and invertebrates at different temporospatial levels on a regular basis to detect possible candidate viruses at their natural source. However, virus surveillance systems can be expensive, costly in terms of finances and resources and inadequate for sampling sufficient numbers of different host species over space and time. Recent publications have presented the concept of a new virus surveillance system, coining the terms "flying biological syringes", "xenosurveillance" and "vector-enabled metagenomics". According to these novel and promising surveillance approaches, viral metagenomics on engorged mosquitoes might reflect the viral diversity of numerous mammals, birds and humans, combined in the mosquitoes' blood meal during feeding on the host. In this review article, we summarize the literature on vector-enabled metagenomics (VEM) techniques and its application in disease surveillance in humans. Furthermore, we highlight the combination of VEM and "invertebrate-derived DNA" (iDNA) analysis to identify the host DNA within the mosquito midgut.

  12. Molecular Detection and Characterization of Gastroenteritis Viruses Occurring Naturally in the Stream Waters of Manaus, Central Amazônia, Brazil▿

    Science.gov (United States)

    Miagostovich, Marize P.; Ferreira, Fabiana F. M.; Guimarães, Flávia R.; Fumian, Túlio M.; Diniz-Mendes, Leonardo; Luz, Sérgio Luiz B.; Silva, Luciete A.; Leite, José Paulo G.

    2008-01-01

    To assess the presence of the four main viruses responsible for human acute gastroenteritis in a hydrographic network impacted by a disordered urbanization process, a 1-year study was performed involving water sample collection from streams in the hydrographic basin surrounding the city of Manaus, Amazonas, Brazil. Thirteen surface water sample collection sites, including different areas of human settlement characterized as urban, rural, and primary forest, located in the Tarumã-Açu, São Raimundo, Educandos, and Puraquequara microbasins, were defined with a global positioning system. At least one virus was detected in 59.6% (31/52) of the water samples analyzed, and rotavirus was the most frequent (44.2%), followed by human adenovirus (30.8%), human astrovirus (15.4%), and norovirus (5.8%). The viral contamination observed mainly in the urban streams reflected the presence of a local high-density population and indicated the gastroenteritis burden from pathogenic viruses in the water, principally due to recreational activities such as bathing. The presence of viral genomes in areas where fecal contamination was not demonstrated by bacterial indicators suggests prolonged virus persistence in aquatic environments and emphasizes the enteric virus group as the most reliable for environmental monitoring. PMID:18065620

  13. Optimization of human immunodeficiency virus treatment during incarceration: viral suppression at the prison gate.

    Science.gov (United States)

    Meyer, Jaimie P; Cepeda, Javier; Wu, Johnny; Trestman, Robert L; Altice, Frederick L; Springer, Sandra A

    2014-05-01

    Human immunodeficiency virus (HIV) management in correctional settings is logistically feasible, but HIV-related outcomes before release have not been recently systematically examined. To evaluate HIV treatment outcomes throughout incarceration, including jail and prison. Retrospective cohort study of longitudinally linked demographic, pharmacy, and laboratory data on 882 prisoners within the Connecticut Department of Correction (2005-2012) with confirmed HIV infection, who were continually incarcerated 90 days or more, had at least 2 HIV-1 RNA and CD4 lymphocyte measurements, and were prescribed antiretroviral therapy. Three electronic databases (correctional, laboratory, and pharmacy) were integrated to assess HIV viral suppression (HIV-1 RNA levels, HIV-1 RNA levels and mean change in CD4 lymphocyte count during incarceration. Demographic characteristics, prescribed pharmacotherapies, receipt of directly observed therapy, and duration of incarceration were analyzed as possible explanatory variables for HIV viral suppression in logistic regression models. Among 882 HIV-infected prisoners with 1185 incarceration periods, mean HIV-1 RNA level decreased by 1.1 log10 and CD4 lymphocyte count increased by 98 cells/µL over time, with a higher proportion achieving viral suppression by release compared with entry (70.0% vs 29.8%; P HIV-1 RNA level, prerelease viral suppression correlated with female sex (adjusted odds ratio, 1.81; 95% CI, 1.26-2.59) and psychiatric disorder severity below the sample median (adjusted odds ratio, 1.50; 95% CI, 1.12-1.99), but not race/ethnicity, incarceration duration, ART regimen or dosing strategy, or directly observed therapy. Though just one-third of HIV-infected prisoners receiving ART entered correctional facilities with viral suppression, HIV treatment was optimized during incarceration, resulting in the majority achieving viral suppression by release. Treatment for HIV within prison is facilitated by a highly structured

  14. Expression of a humanized viral 2A-mediated lux operon efficiently generates autonomous bioluminescence in human cells.

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    Xu, Tingting; Ripp, Steven; Sayler, Gary S; Close, Dan M

    2014-01-01

    Expression of autonomous bioluminescence from human cells was previously reported to be impossible, suggesting that all bioluminescent-based mammalian reporter systems must therefore require application of a potentially influential chemical substrate. While this was disproven when the bacterial luciferase (lux) cassette was demonstrated to function in a human cell, its expression required multiple genetic constructs, was functional in only a single cell type, and generated a significantly reduced signal compared to substrate-requiring systems. Here we investigate the use of a humanized, viral 2A-linked lux genetic architecture for the efficient introduction of an autobioluminescent phenotype across a variety of human cell lines. The lux cassette was codon optimized and assembled into a synthetic human expression operon using viral 2A elements as linker regions. Human kidney, breast cancer, and colorectal cancer cell lines were both transiently and stably transfected with the humanized operon and the resulting autobioluminescent phenotype was evaluated using common imaging instrumentation. Autobioluminescent cells were screened for cytotoxic effects resulting from lux expression and their utility as bioreporters was evaluated through the demonstration of repeated monitoring of single populations over a prolonged period using both a modified E-SCREEN assay for estrogen detection and a classical cytotoxic compound detection assay for the antibiotic Zeocin. Furthermore, the use of self-directed bioluminescent initiation in response to target detection was assessed to determine its amenability towards deployment as fully autonomous sensors. In all cases, bioluminescent measurements were supported with traditional genetic and transcriptomic evaluations. Our results demonstrate that the viral 2A-linked, humanized lux genetic architecture successfully produced autobioluminescent phenotypes in all cell lines tested without the induction of cytotoxicity. This

  15. Expression of a humanized viral 2A-mediated lux operon efficiently generates autonomous bioluminescence in human cells.

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    Tingting Xu

    Full Text Available Expression of autonomous bioluminescence from human cells was previously reported to be impossible, suggesting that all bioluminescent-based mammalian reporter systems must therefore require application of a potentially influential chemical substrate. While this was disproven when the bacterial luciferase (lux cassette was demonstrated to function in a human cell, its expression required multiple genetic constructs, was functional in only a single cell type, and generated a significantly reduced signal compared to substrate-requiring systems. Here we investigate the use of a humanized, viral 2A-linked lux genetic architecture for the efficient introduction of an autobioluminescent phenotype across a variety of human cell lines.The lux cassette was codon optimized and assembled into a synthetic human expression operon using viral 2A elements as linker regions. Human kidney, breast cancer, and colorectal cancer cell lines were both transiently and stably transfected with the humanized operon and the resulting autobioluminescent phenotype was evaluated using common imaging instrumentation. Autobioluminescent cells were screened for cytotoxic effects resulting from lux expression and their utility as bioreporters was evaluated through the demonstration of repeated monitoring of single populations over a prolonged period using both a modified E-SCREEN assay for estrogen detection and a classical cytotoxic compound detection assay for the antibiotic Zeocin. Furthermore, the use of self-directed bioluminescent initiation in response to target detection was assessed to determine its amenability towards deployment as fully autonomous sensors. In all cases, bioluminescent measurements were supported with traditional genetic and transcriptomic evaluations.Our results demonstrate that the viral 2A-linked, humanized lux genetic architecture successfully produced autobioluminescent phenotypes in all cell lines tested without the induction of cytotoxicity

  16. Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2

    Science.gov (United States)

    Lemey, Philippe; Rambaut, Andrew; Bedford, Trevor; Faria, Nuno; Bielejec, Filip; Baele, Guy; Russell, Colin A.; Smith, Derek J.; Pybus, Oliver G.; Brockmann, Dirk; Suchard, Marc A.

    2014-01-01

    Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control

  17. A Gastroenteritis Outbreak Caused by Noroviruses in Greece

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    Yiannis Alamanos

    2011-08-01

    Full Text Available In June 2006, an outbreak alert regarding cases of acute gastroenteritis in a region in North Eastern Greece (population 100,882 inhabitants, triggered investigations to guide control measures. The outbreak started the first days of June, and peaked in July. A descriptive epidemiological study, a virological characterization of the viral agent identified from cases as well as a phylogenetic analysis was performed. From June 5 to September 3, 2006 (weeks 23–44, 1,640 cases of gastroenteritis (45.2% male and 54.8% female, aged 3 months to 89 years were reported. The overall attack rate for the period was 16.3 cases/1,000 inhabitants. About 57% of cases observed were under the age of 15 years. Αnalysis of faecal samples identified Norovirus GII strains. Fifteen different Norovirus GII strains were recorded, presenting a homology of 94.8% (86–97% to GII strains obtained from GenBank. The long duration of the outbreak suggests an important role of person-to-person transmission, while the emergence of the outbreak was possibly due to contaminated potable water, although no viruses were detected in any tested water samples. This outbreak underscores the need for a national surveillance system for acute non-bacterial gastroenteritis outbreaks.

  18. Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

    Science.gov (United States)

    Alcendor, Donald J

    2017-07-15

    Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study.

  19. A Novel system for evaluating the interaction between human norovirus and receptors

    Science.gov (United States)

    Human noroviruses (HuNoVs) are major pathogens for acute nonbacterial gastroenteritis outbreaks. Many aspects of HuNoVs are poorly understood due to both the current inability to culture HuNoVs, and the lack of efficient small animal models. Recombinant HuNoV viral capsid proteins and/or P particles...

  20. Comparing human T cell and NK cell responses in viral-based malaria vaccine trials.

    Science.gov (United States)

    Berthoud, Tamara K; Fletcher, Helen; Porter, David; Thompson, Fiona; Hill, Adrian V S; Todryk, Stephen M

    2009-12-10

    Vaccination with viral-based vaccines continues to hold promise for the prevention of malaria. Whilst antigen-specific T cell responses are considered a major aim of such an approach, a role for induced NK cells as anti-malarial effector cells, or in shaping T cell responses, has received less attention. In this study naïve human volunteers were vaccinated in a prime-boost vaccination regimen comprising recombinant viral vectors fowlpox (FP9) and modified vaccinia Ankara (MVA) encoding liver-stage antigens, or a virosome vaccine. Significant T cell responses specific for the vectored vaccine antigens were demonstrated by IFNgamma ELISPOT and intracellular cytokine staining (ICS) for IFNgamma and IL-2, the ICS being associated with increased time to parasitaemia following subsequent challenge. Numbers of CD56(bright) lymphocytes increased significantly following vaccination, as did CD3(+) CD56(+) lymphocytes, whilst CD56(dim) cells did not. No such increases were seen with the virosome vaccine. There was no significant correlation of these CD56(+) populations with the antigen-specific T cell responses nor time to parasitaemia. To investigate pathways of immune activation that could contribute to these lymphocyte responses, viral vectors were shown in vitro to efficiently infect APCs but not lymphocytes, and stimulated inflammatory cytokines such as type I interferons. In conclusion, measuring antigen-specific T cells is more meaningful than NK cells in these vaccination regimens.

  1. Aptamer-Based Therapeutics: New Approaches to Combat Human Viral Diseases

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    Ka-To Shum

    2013-11-01

    Full Text Available Viruses replicate inside the cells of an organism and continuously evolve to contend with an ever-changing environment. Many life-threatening diseases, such as AIDS, SARS, hepatitis and some cancers, are caused by viruses. Because viruses have small genome sizes and high mutability, there is currently a lack of and an urgent need for effective treatment for many viral pathogens. One approach that has recently received much attention is aptamer-based therapeutics. Aptamer technology has high target specificity and versatility, i.e., any viral proteins could potentially be targeted. Consequently, new aptamer-based therapeutics have the potential to lead a revolution in the development of anti-infective drugs. Additionally, aptamers can potentially bind any targets and any pathogen that is theoretically amenable to rapid targeting, making aptamers invaluable tools for treating a wide range of diseases. This review will provide a broad, comprehensive overview of viral therapies that use aptamers. The aptamer selection process will be described, followed by an explanation of the potential for treating virus infection by aptamers. Recent progress and prospective use of aptamers against a large variety of human viruses, such as HIV-1, HCV, HBV, SCoV, Rabies virus, HPV, HSV and influenza virus, with particular focus on clinical development of aptamers will also be described. Finally, we will discuss the challenges of advancing antiviral aptamer therapeutics and prospects for future success.

  2. Community-Acquired Rotavirus Gastroenteritis Compared with Adenovirus and Norovirus Gastroenteritis in Italian Children: A Pedianet Study

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    D. Donà

    2016-01-01

    Full Text Available Background. Rotavirus (RV is the commonest pathogen in the hospital and primary care settings, followed by Adenovirus (AV and Norovirus (NV. Only few studies that assess the burden of RV gastroenteritis at the community level have been carried out. Objectives. To estimate incidence, disease characteristics, seasonal distribution, and working days lost by parents of RV, AV, and NV gastroenteritis leading to a family pediatrician (FP visit among children < 5 years. Methods. 12-month, observational, prospective, FP-based study has been carried out using Pedianet database. Results. RVGE incidence was 1.04 per 100 person-years with the highest incidence in the first 2 years of life. Incidences of AVGEs (1.74 and NVGEs (1.51 were slightly higher with similar characteristics regarding age distribution and symptoms. Risk of hospitalisation, access to emergency room (ER, and workdays lost from parents were not significantly different in RVGEs compared to the other viral infections. Conclusions. Features of RVGE in terms of hospitalisation length and indirect cost are lower than those reported in previous studies. Results of the present study reflect the large variability of data present in the literature. This observation underlines the utility of primary care networks for AGE surveillance and further studies on community-acquired gastroenteritis in children.

  3. Nuclear domain 10 components upregulated via interferon during human cytomegalovirus infection potently regulate viral infection.

    Science.gov (United States)

    Ashley, Caroline L; Glass, Mandy S; Abendroth, Allison; McSharry, Brian P; Slobedman, Barry

    2017-07-01

    Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that causes life-threatening disease in immunocompromised and immunonaïve individuals. Type I interferons (IFNs) are crucial molecules in the innate immune response to HCMV and are also known to upregulate several components of the interchromosomal multiprotein aggregates collectively referred to as nuclear domain 10 (ND10). In the context of herpesvirus infection, ND10 components are known to restrict gene expression. This raises the question as to whether key ND10 components (PML, Sp100 and hDaxx) act as anti-viral IFN-stimulated genes (ISGs) during HCMV infection. In this study, analysis of ND10 component transcription during HCMV infection demonstrated that PML and Sp100 were significantly upregulated whilst hDaxx expression remained unchanged. In cells engineered to block the production of, or response to, type I IFNs, upregulation of PML and Sp100 was not detected during HCMV infection. Furthermore, pre-treatment with an IFN-β neutralizing antibody inhibited upregulation of PML and Sp100 during both infection and treatment with HCMV-infected cell supernatant. The significance of ND10 components functioning as anti-viral ISGs during HCMV infection was determined through knockdown of PML, Sp100 and hDaxx. ND10 knockdown cells were significantly more permissive to HCMV infection, as previously described but, in contrast to control cells, could support HCMV plaque formation following IFN-β pre-treatment. This ability of HCMV to overcome the potently anti-viral effects of IFN-β in ND10 expression deficient cells provides evidence that ND10 component upregulation is a key mediator of the anti-viral activity of IFN-β.

  4. Molecular detection of human papillomavirus and viral DNA load after radiotherapy for cervical carcinomas.

    Science.gov (United States)

    Kahla, Saloua; Kochbati, Lotfi; Sarraj, Sana; Ben Daya, Imen; Maalej, Mongi; Oueslati, Ridha

    2016-10-13

    Infection with high-risk types of human papillomavirus (HPV) is a necessary cause for cervical carcinoma. Radiation therapy together with surgery is the most effective treatment. The purpose of this study was to investigate the molecular basis of the response to radiotherapy in cervical cancer cells. Tumor cells were obtained from biopsies of 44 cervical cancers, collected before and after radiotherapy. The presence of HPV was analyzed by polymerase chain reaction (PCR) using primers specific for the L1 region. The prevalence of HPV was 70.4%, with HPV16 being the most common (54.5%) and HPV18 the second (15.9%). Our analyses show that ionizing radiation does not influence HPV detection, as the percentage of HPV-positive biopsies was similar in patients before and after radiotherapy (HPV16 60% vs. 51.7% and HPV18 20% vs. 13.7%, respectively). However, the detection of HPV did vary by tumor stage, with the highest proportion observed in late-stage tumors (HPV16 and HPV18 in 80% and 60% of stage III tumors, respectively). We also found that HPV viral load is influenced by radiotherapy and tumor stage, with the highest viral loads in late-stage tumors (stage III) after 1 day since radiotherapy (p<0.05). According to Kaplan-Meier curves, higher HPV viral load was associated with significantly shortened progression-free survival (p = 0.04). Our data provide prospective evidence that ionizing radiation can affect the HPV viral load and this might offer the best strategies for assessment of therapeutic efficacy.

  5. Viral load affects the immune response to HBV in mice with humanized immune system and liver.

    Science.gov (United States)

    Dusséaux, Mathilde; Masse-Ranson, Guillemette; Darche, Sylvie; Ahodantin, James; Li, Yan; Fiquet, Oriane; Beaumont, Elodie; Moreau, Pierrick; Rivière, Lise; Neuveut, Christine; Soussan, Patrick; Roingeard, Philippe; Kremsdorf, Dina; Di Santo, James P; Strick-Marchand, Helene

    2017-08-26

    Hepatitis B virus (HBV) infects hepatocytes, but the mechanisms of the immune response against the virus, and how it affects disease progression, are unclear. We performed studies with BALB/c Rag2(-/-)Il2rg(-/-)Sirpa(NOD)Alb-uPA(tg/tg) mice, stably engrafted with human hepatocytes (HUHEP) with or without a human immune system (HIS). HUHEP and HIS-HUHEP mice were given an intraperitoneal injection of HBV. Mononuclear cells were isolated from spleen and liver for analysis by flow cytometry. Liver was analyzed by immunohistochemistry and mRNA levels were measured by quantitative reverse transcription PCR. Plasma levels of HBV DNA was quantified by quantitative PCR, and antigen-specific antibodies were detected by immunocytochemistry of HBV transfected BHK-21 cells. Following HBV infection, a complete viral life cycle, with production of HBV DNA, hepatitis B e, core (HBc) and surface (HBs) antigens, and covalently closed circular DNA, was observed in HUHEP and HIS-HUHEP mice. HBV replicated unrestricted in HUHEP mice resulting in high viral titers without pathologic effects. In contrast, HBV-infected HIS-HUHEP mice developed chronic hepatitis with 10-fold lower titers and antigen-specific IgGs, (anti-HBs, anti-HBc), consistent with partial immune control. HBV-infected HIS-HUHEP livers contained infiltrating Kupffer cells, mature activated natural killer cells (CD69+), and PD-1+ effector memory T cells (CD45RO+). Reducing the viral inoculum resulted in more efficient immune control. Plasma from HBV-infected HIS-HUHEP mice had increased levels of inflammatory and immune-suppressive cytokines (C-X-C motif chemokine ligand 10 and interleukin 10), which correlated with populations of intrahepatic CD4+ T cells (CD45RO+PD-1+). Mice with high levels of viremia had HBV-infected liver progenitor cells. Giving the mice the nucleoside analogue entecavir reduced viral loads and decreased liver inflammation. In HIS-HUHEP mice, HBV infection completes a full life cycle and

  6. PD-1 blockade in chronically HIV-1-infected humanized mice suppresses viral loads.

    Directory of Open Access Journals (Sweden)

    Edward Seung

    Full Text Available An estimated 34 million people are living with HIV worldwide (UNAIDS, 2012, with the number of infected persons rising every year. Increases in HIV prevalence have resulted not only from new infections, but also from increases in the survival of HIV-infected persons produced by effective anti-retroviral therapies. Augmentation of anti-viral immune responses may be able to further increase the survival of HIV-infected persons. One strategy to augment these responses is to reinvigorate exhausted anti-HIV immune cells present in chronically infected persons. The PD-1-PD-L1 pathway has been implicated in the exhaustion of virus-specific T cells during chronic HIV infection. Inhibition of PD-1 signaling using blocking anti-PD-1 antibodies has been shown to reduce simian immunodeficiency virus (SIV loads in monkeys. We now show that PD-1 blockade can improve control of HIV replication in vivo in an animal model. BLT (Bone marrow-Liver-Thymus humanized mice chronically infected with HIV-1 were treated with an anti-PD-1 antibody over a 10-day period. The PD-1 blockade resulted in a very significant 45-fold reduction in HIV viral loads in humanized mice with high CD8(+ T cell expression of PD-1, compared to controls at 4 weeks post-treatment. The anti-PD-1 antibody treatment also resulted in a significant increase in CD8(+ T cells. PD-1 blockade did not affect T cell expression of other inhibitory receptors co-expressed with PD-1, including CD244, CD160 and LAG-3, and did not appear to affect virus-specific humoral immune responses. These data demonstrate that inhibiting PD-1 signaling can reduce HIV viral loads in vivo in the humanized BLT mouse model, suggesting that blockade of the PD-1-PD-L1 pathway may have therapeutic potential in the treatment of patients already infected with the AIDS virus.

  7. Characterization of the methylation patterns in human papillomavirus type 16 viral DNA in head and neck cancers.

    Science.gov (United States)

    Park, Il-Seok; Chang, Xiaofei; Loyo, Myriam; Wu, Gaosong; Chuang, Alice; Kim, Myoung Sook; Chae, Young Kwang; Lyford-Pike, Sofia; Westra, William H; Saunders, John R; Sidransky, David; Pai, Sara Isabel

    2011-02-01

    Human papillomavirus (HPV) type 16 can integrate into the host genome, thereby rendering the viral coding genes susceptible to epigenetic modification. Using bisulfite genomic sequencing, we determined the methylation status of all 110 CpG sites within the viral epigenome in advanced stage III/IV HPV-16-associated head and neck cancers. We found that the viral genome was hypomethylated in the majority of head and neck cancers, in particular within the viral regulatory region, long control region (LCR), which controls transcription of the E6 and E7 oncogenes. The hypomethylation status of LCR correlated with detectable levels of E6 and E7 expression, which suggests that the tumors may still be dependent on these viral oncogenes to maintain the malignant phenotype. In addition to the methylation status of LCR, we report other potential factors which may influence intratumoral E6 and E7 expression including viral copy number and integration site. We were able to detect the viral epigenetic alterations in sampled body fluids, such as serum and saliva, which correlated with the changes observed in the primary tumors. Because viral epigenetic changes occur in the setting of viral integration into the human genome, the detection of methylated HPV genes in the serum and/or saliva may have diagnostic potential for early detection strategies of viral integration and assessment of risk for cancer development in high-risk individuals. Our findings also support continued targeting of the E6 and/or E7 antigens through various vaccine strategies against HPV-associated cancers. ©2011 AACR.

  8. Acute gastroenteritis and enteric viruses in hospitalised children in southern Brazil: aetiology, seasonality and clinical outcomes

    Directory of Open Access Journals (Sweden)

    Sonia Maria Raboni

    2014-07-01

    Full Text Available Viral acute gastroenteritis (AG is a significant cause of hospitalisation in children younger than five years. Group A rotavirus (RVA is responsible for 30% of these cases. Following the introduction of RVA immunisation in Brazil in 2006, a decreased circulation of this virus has been observed. However, AG remains an important cause of hospitalisation of paediatric patients and only limited data are available regarding the role of other enteric viruses in these cases. We conducted a prospective study of paediatric patients hospitalised for AG. Stool samples were collected to investigate human adenovirus (HAdV, RVA, norovirus (NoV and astrovirus (AstV. NoV typing was performed by nucleotide sequencing and phylogenetic analysis. From the 225 samples tested, 60 (26% were positive for at least one viral agent. HAdV, NoV, RVA and AstV were detected in 16%, 8%, 6% and 0% of the samples, respectively. Mixed infections were found in nine patients: HAdV/RVA (5, HAdV/NoV (3 and HAdV/NoV/RVA (1. The frequency of fever and lymphocytosis was significantly higher in virus-infected patients. Phylogenetic analysis of NoV indicated that all of these viruses belonged to genotype GII.4. The significant frequency of these pathogens in patients with AG highlights the need to routinely implement laboratory investigations.

  9. Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children.

    Science.gov (United States)

    Zhou, Lili; Zheng, Shouyan; Xiao, Qiuyan; Ren, Luo; Xie, Xiaohong; Luo, Jian; Wang, Lijia; Huang, Ailong; Liu, Wei; Liu, Enmei

    2014-07-30

    Human bocavirus is a newly discovered parvovirus. Multiple studies have confirmed the presence of human bocavirus1 (HBoV1) in respiratory tract samples of children. The viral load, presentation of single detection and its role as a causative agent of severe respiratory tract infections have not been thoroughly elucidated. We investigated the presence of HBoV1 by quantitative polymerase chain reaction (PCR) of nasopharyngeal aspirate specimens from 1229 children hospitalized for respiratory tract infections. The samples were analyzed for 15 respiratory viruses by PCR and 7 respiratory viruses by viral culture. At least one virus was detected in 652 (53.1%) of 1229 children, and two or more viruses were detected in 266 (21.6%) children. HBoV1 was detected in 127 children (10.3%), in which 66/127 (52%) of the cases were the only HBoV1 virus detected. Seasonal variation was observed with a high HBoV1 infection rate in summer. A cutoff value of 107 copies/mL was used to distinguish high and low HBoV1 viral loads in the nasopharyngeal aspirates. High viral loads of HBoV1 were noted predominantly in the absence of other viral agents (28/39, 71.8%) whereas there was primarily co-detection in cases of low HBoV1 viral loads (50/88, 56.8%). There were no differences in the clinical symptoms and severity between HBoV1 single detection and co-detection. In cases of HBoV1 single detection, the high viral load group was more prevalent among children with dyspnea and wheezing than was the low viral load group (42.9% vs. 23.7%, P = 0.036; 60.7% vs. 31.6%, P = 0.018). In clinical severity, a significant difference was recorded (25.0% vs. 5.3%, P = 0.003) between high viral load and low viral load groups. Of the HBoV1 positive patients associated with severe respiratory tract infections, 10/18 (55.6%) patients belonged to the HBoV1 high viral load group, and 7/10 (70%) patients had cases of HBoV1 single detection. HBoV1 at a high viral load is not frequently found in co

  10. Molecular epidemiology of enteric viruses in patients with acute gastroenteritis in Aichi prefecture, Japan, 2008/09-2013/14.

    Science.gov (United States)

    Nakamura, Noriko; Kobayashi, Shinichi; Minagawa, Hiroko; Matsushita, Tadashi; Sugiura, Wataru; Iwatani, Yasumasa

    2016-07-01

    Acute gastroenteritis is a critical infectious disease that affects infants and young children throughout the world, including Japan. This retrospective study was conducted from September 2008 to August 2014 (six seasons: 2008/09-2013/14) to investigate the incidence of enteric viruses responsible for 1,871 cases of acute gastroenteritis in Aichi prefecture, Japan. Of the 1,871 cases, 1,100 enteric viruses were detected in 978 samples, of which strains from norovirus (NoV) genogroup II (60.9%) were the most commonly detected, followed by strains of rotavirus A (RVA) (23.2%), adenovirus (AdV) type 41 (8.2%), sapovirus (SaV) (3.6%), human astrovirus (HAstV) (2.8%), and NoV genogroup I (1.3%). Sequencing of the NoV genogroup II (GII) strains revealed that GII.4 was the most common genotype, although four different GII.4 variants were also identified. The most common G-genotype of RVA was G1 (63.9%), followed by G3 (27.1%), G2 (4.7%) and G9 (4.3%). Three genogroups of SaV strains were found: GI (80.0%), GII (15.0%), and GV (5.0%). HAstV strains were genotyped as HAstV-1 (80.6%), HAstV-8 (16.1%), and HAstV-3 (3.2%). These results show that NoV GII was the leading cause of sporadic acute viral gastroenteritis, although a variety of enteric viruses were detected during the six-season surveillance period. © 2015 Wiley Periodicals, Inc.

  11. Adeno-associated viral vector transduction of human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Stender, Stefan; Murphy, Mary; O'Brien, Tim

    2007-01-01

    Mesenchymal stem cells (MSCs) have received considerable attention in the emerging field of regenerative medicine. One aspect of MSC research focuses on genetically modifying the cells with the aim of enhancing their regenerative potential. Adeno-associated virus (AAV) holds promise as a vector...... in human MSCs and to assess whether AAV transduction affects MSC multipotentiality. The results indicated that human MSCs could indeed be transiently transduced in vitro by the AAV2 vector with efficiencies of up to 65%. The percentage of GFP-positive cells peaked at 4 days post-transduction and declined...... rapidly towards 0% after day 8. The level of transgene expression in the GFP-positive population increased 4-fold over a 10,000 fold viral dose increase. This dose-response contrasted with the 200-fold increase observed in similarly transduced 293-cells, indicating a relatively restricted transgene...

  12. Gastroenteritis outbreak associated with faecal shedding of canine norovirus in a Portuguese kennel following introduction of imported dogs from Russia.

    Science.gov (United States)

    Mesquita, J R; Nascimento, M S J

    2012-10-01

    We describe an outbreak of acute gastroenteritis (AGE) in dogs in March 2011 in a Portuguese kennel after the introduction of imported Russian dogs. Canine norovirus was detected in faecal samples of all dogs with AGE symptoms. Partial sequence analysis of the RT-PCR products confirmed that all canine norovirus strains were identical. The canine norovirus infection disseminated rapidly in 2 days to all dogs in the kennel demonstrating the highly contagious nature of this virus. The incubation period was <48 h, the diarrhoeal disease was self-limiting and the viral shedding lasted <7 days. Overall, the epidemiological features of this outbreak resembled those of human norovirus infections. © 2011 Blackwell Verlag GmbH.

  13. Non-human Primate Schlafen11 Inhibits Production of Both Host and Viral Proteins.

    Directory of Open Access Journals (Sweden)

    Alex C Stabell

    2016-12-01

    Full Text Available Schlafen11 (encoded by the SLFN11 gene has been shown to inhibit the accumulation of HIV-1 proteins. We show that the SLFN11 gene is under positive selection in simian primates and is species-specific in its activity against HIV-1. The activity of human Schlafen11 is relatively weak compared to that of some other primate versions of this protein, with the versions encoded by chimpanzee, orangutan, gibbon, and marmoset being particularly potent inhibitors of HIV-1 protein production. Interestingly, we find that Schlafen11 is functional in the absence of infection and reduces protein production from certain non-viral (GFP and even host (Vinculin and GAPDH transcripts. This suggests that Schlafen11 may just generally block protein production from non-codon optimized transcripts. Because Schlafen11 is an interferon-stimulated gene with a broad ability to inhibit protein production from many host and viral transcripts, its role may be to create a general antiviral state in the cell. Interestingly, the strong inhibitors such as marmoset Schlafen11 consistently block protein production better than weak primate Schlafen11 proteins, regardless of the virus or host target being analyzed. Further, we show that the residues to which species-specific differences in Schlafen11 potency map are distinct from residues that have been targeted by positive selection. We speculate that the positive selection of SLFN11 could have been driven by a number of different factors, including interaction with one or more viral antagonists that have yet to be identified.

  14. Human poly- and cross-reactive anti-viral antibodies and their impact on protection and pathology.

    Science.gov (United States)

    Warter, Lucile; Appanna, Ramapraba; Fink, Katja

    2012-09-01

    Anti-viral immune responses have been studied extensively in order to inform rational vaccine design. Following viral infection, the balance of pathologic and protective antibody responses in the host can critically influence clinical outcomes. Comparisons of the different classes of antibodies produced after acute or chronic viral infections have uncovered common features of anti-viral responses, but these analyses have also revealed temporal differences in neutralizing antibody production, variable neutralization potency and differential induction of cross-reactive antibodies. Cross-reactive antibodies are known to play crucial protective roles in host responses to chronic viral infections; recent studies in human immunodeficiency virus long-term controllers have identified a novel class of broadly neutralizing antibodies generated from highly mutated and selected memory B cells. Here, we summarize the various roles played by cross- and poly-reactive antibodies in acute and persistent viral infections, with a focus on the potential contribution of these antibodies to dengue virus (DENV) immunopathology and host protection. Since host antibodies profoundly alter the course of viral infections, effective DENV vaccine design will require a better understanding of the origin, affinity maturation and protective potential of the poly-reactive and cross-reactive antibodies induced by different interventions.

  15. A preliminary study of viral metagenomics of French bat species in contact with humans: identification of new mammalian viruses.

    Science.gov (United States)

    Dacheux, Laurent; Cervantes-Gonzalez, Minerva; Guigon, Ghislaine; Thiberge, Jean-Michel; Vandenbogaert, Mathias; Maufrais, Corinne; Caro, Valérie; Bourhy, Hervé

    2014-01-01

    The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.

  16. A preliminary study of viral metagenomics of French bat species in contact with humans: identification of new mammalian viruses.

    Directory of Open Access Journals (Sweden)

    Laurent Dacheux

    Full Text Available The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome. We determined the viral diversity of five different French insectivorous bat species (nine specimens in total in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs. Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae. In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.

  17. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption

    Science.gov (United States)

    Scheid, Johannes F.; Horwitz, Joshua A.; Bar-On, Yotam; Kreider, Edward F.; Lu, Ching-Lan; Lorenzi, Julio C. C.; Feldmann, Anna; Braunschweig, Malte; Nogueira, Lilian; Oliveira, Thiago; Shimeliovich, Irina; Patel, Roshni; Burke, Leah; Cohen, Yehuda Z.; Hadrigan, Sonya; Settler, Allison; Witmer-Pack, Maggi; West, Anthony P.; Juelg, Boris; Keler, Tibor; Hawthorne, Thomas; Zingman, Barry; Gulick, Roy M.; Pfeifer, Nico; Learn, Gerald H.; Seaman, Michael S.; Bjorkman, Pamela J.; Klein, Florian; Schlesinger, Sarah J.; Walker, Bruce D.; Hahn, Beatrice H.; Nussenzweig, Michel C.; Caskey, Marina

    2016-01-01

    Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117, a broad and potent neutralizing antibody (bNAb) against the CD4 binding site of HIV-1 Env1, in the setting of analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Two or four 30 mg kg−1 infusions of 3BNC117, separated by 3 or 2 weeks, respectively, are generally well tolerated. Infusions are associated with a delay in viral rebound for 5–9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals, emerging viruses show increased resistance, indicating escape. However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg ml−1, and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9–19 weeks. We conclude that administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans. PMID:27338952

  18. Interaction of extremophilic archaeal viruses with human and mouse complement system and viral biodistribution in mice.

    Science.gov (United States)

    Wu, Linping; Uldahl, Kristine Buch; Chen, Fangfang; Benasutti, Halli; Logvinski, Deborah; Vu, Vivian; Banda, Nirmal K; Peng, Xu; Simberg, Dmitri; Moghimi, Seyed Moein

    2017-10-01

    Archaeal viruses offer exceptional biophysical properties for modification and exploration of their potential in bionanotechnology, bioengineering and nanotherapeutic developments. However, the interaction of archaeal viruses with elements of the innate immune system has not been explored, which is a necessary prerequisite if their potential for biomedical applications to be realized. Here we show complement activation through lectin (via direct binding of MBL/MASPs) and alternative pathways by two extremophilic archaeal viruses (Sulfolobus monocaudavirus 1 and Sulfolobus spindle-shaped virus 2) in human serum. We further show some differences in initiation of complement activation pathways between these viruses. Since, Sulfolobus monocaudavirus 1 was capable of directly triggering the alternative pathway, we also demonstrate that the complement regulator factor H has no affinity for the viral surface, but factor H deposition is purely C3-dependent. This suggests that unlike some virulent pathogens Sulfolobus monocaudavirus 1 does not acquire factor H for protection. Complement activation with Sulfolobus monocaudavirus 1 also proceeds in murine sera through MBL-A/C as well as factor D-dependent manner, but C3 deficiency has no overall effect on viral clearance by organs of the reticuloendothelial system on intravenous injection. However, splenic deposition was significantly higher in C3 knockout animals compared with the corresponding wild type mice. We discuss the potential application of these viruses in biomedicine in relation to their complement activating properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution.

    Science.gov (United States)

    Ogimi, Chikara; Greninger, Alexander L; Waghmare, Alpana A; Kuypers, Jane M; Shean, Ryan C; Xie, Hu; Leisenring, Wendy M; Stevens-Ayers, Terry L; Jerome, Keith R; Englund, Janet A; Boeckh, Michael

    2017-07-15

    Recent data suggest that human coronavirus (HCoV) pneumonia is associated with significant mortality in hematopoietic cell transplant (HCT) recipients. Investigation of risk factors for prolonged shedding and intrahost genome evolution may provide critical information for development of novel therapeutics. We retrospectively reviewed HCT recipients with HCoV detected in nasal samples by polymerase chain reaction (PCR). HCoV strains were identified using strain-specific PCR. Shedding duration was defined as time between first positive and first negative sample. Logistic regression analyses were performed to evaluate factors for prolonged shedding (≥21 days). Metagenomic next-generation sequencing (mNGS) was conducted when ≥4 samples with cycle threshold values of <28 were available. Seventeen of 44 patients had prolonged shedding. Among 31 available samples, 35% were OC43, 32% were NL63, 19% were HKU1, and 13% were 229E; median shedding duration was similar between strains (P = .79). Bivariable logistic regression analyses suggested that high viral load, receipt of high-dose steroids, and myeloablative conditioning were associated with prolonged shedding. mNGS among 5 subjects showed single-nucleotide polymorphisms from OC43 and NL63 starting 1 month following onset of shedding. High viral load, high-dose steroids, and myeloablative conditioning were associated with prolonged shedding of HCoV in HCT recipients. Genome changes were consistent with the expected molecular clock of HCoV.

  20. Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems

    Directory of Open Access Journals (Sweden)

    Marta Trevisan

    2015-07-01

    Full Text Available The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs, which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host–pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

  1. Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems.

    Science.gov (United States)

    Trevisan, Marta; Sinigaglia, Alessandro; Desole, Giovanna; Berto, Alessandro; Pacenti, Monia; Palù, Giorgio; Barzon, Luisa

    2015-07-13

    The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs), which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host-pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

  2. Investigation of the Enteric Adenovirus Antigen Frequency by Immunochromotographic Method in Children with Acute Gastroenteritis

    Directory of Open Access Journals (Sweden)

    Orhan Akpınar

    2017-08-01

    Full Text Available Objective: Gastroenteritis is the third common cause of death due to infections. After rotavirus, adenoviruses are also one of the reasons frequently seen in gastroenteritis in infants and children. This study is performed to determine the incidence of enteric virus serotype 40 and 41 in children with acute gastroenteritis in order to enable prompt and appropriate treatment. Materials and Methods: Stool specimens of patients who attended our clinic with a diagnosis of acute gastroenteritis between January 2013 and December 2013 were examined for the presence of enteric adenovirus (Ad40 and Ad41 antigen using immunochromatographic methods. Results: One hundred and two stool samples from 3206 were positive for adenovirus antigens. Adenovirus antigen positive-patients aged 0-5 years constituted 82.3% of patients. Adenovirus infections were observed in all seasons of the year. Conclusion: In our country, the epidemiology of adenovirus infection is not known very well. According to the data we obtained from the results of this study, we assume that idntifying viral agent in patients with diarrhea in an accurate, prompt and reliable way can prevent unnecessary antibiotic use and can contribute seroepidemiologic data in childhood gastroenteritis in our region.

  3. Association between high nasopharyngeal viral load and disease severity in children with human metapneumovirus infection

    NARCIS (Netherlands)

    Bosis, Samantha; Esposito, Susanna; Osterhaus, Albert D. M. E.; Tremolati, Elena; Begliatti, Enrica; Tagliabue, Claudia; Corti, Fabiola; Principi, Nicola; Niesters, Hubert G. M.

    Background: Previous studies have shown that viral genotype and viral load may play a significant role in the pathogenesis of viral infections. Objectives: The aim of this study was to evaluate these aspects of hMPV infections in children and their household contacts. Study design: Between I

  4. Food webs in the human body: linking ecological theory to viral dynamics.

    Science.gov (United States)

    Murall, Carmen Lía; McCann, Kevin S; Bauch, Chris T

    2012-01-01

    The dynamics of in-host infections are central to predicting the progression of natural infections and the effectiveness of drugs or vaccines, however, they are not well understood. Here, we apply food web theory to in-host disease networks of the human body that are structured similarly to food web models that treat both predation and competition simultaneously. We show that in-host trade-offs, an under-studied aspect of disease ecology, are fundamental to understanding the outcomes of competing viral strains under differential immune responses. Further, and importantly, our analysis shows that the outcome of competition between virulent and non-virulent strains can be highly contingent on the abiotic conditions prevailing in the human body. These results suggest the alarming idea that even subtle behavioral changes that alter the human body (e.g. weight gain, smoking) may switch the environmental conditions in a manner that suddenly allows a virulent strain to dominate and replace less virulent strains. These ecological results therefore cast new light on the control of disease in the human body, and highlight the importance of longitudinal empirical studies across host variation gradients, as well as, of studies focused on delineating life history trade-offs within hosts.

  5. Infidelity of translation of encephalomyocarditis viral RNA with tRNA from human malignant trophoblastic cells

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, O.K.; Kuchino, Y.

    1977-09-23

    We have investigated tRNA from the human malignant trophoblastic cells (BeWo cell) and human chorionic tissue for the translation of specific mRNAs, in a tRNA-dependent protein synthesizing system from Ehrlich ascites cells. BeWo cell tRNA and chorionic tRNA supported oviduct mRNA or encephalomyocarditis (EMC) viral RNA directed amino acid incorporation into polypeptides equally effectively. Polypeptides synthesized with oviduct mRNA and tRNA from both sources were identical upon sodium dodecylsulfate polyacrylamide gel electrophoresis. But the EMC RNA directed polypeptides synthesized with BeWo cell tRNA were different from those synthesized with chorionic tRNA. A polypeptide (molecular weight 58,000) was apparently not synthesized and the synthesis of a faster moving component (molecular weight, 14,000) was enhanced when BeWo cell tRNA was used. These results imply a functional difference in tRNA from human malignant cells compared to their normal counterpart.

  6. Direct Neural Conversion from Human Fibroblasts Using Self-Regulating and Nonintegrating Viral Vectors

    Directory of Open Access Journals (Sweden)

    Shong Lau

    2014-12-01

    Full Text Available Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and self-regulated conversion system that rids problems associated with the integration of viral transgenes into the host genome. These modifications make the system suitable for clinical use and therefore represent a major step forward in the development of induced neurons for cell therapy.

  7. Modeling Zika plasma viral dynamics in non-human primates: insights into viral pathogenesis and antiviral strategies

    Energy Technology Data Exchange (ETDEWEB)

    Best, Katharine [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Guedj, Jeremie [Univ. of Paris (France). IAME; Madelain, Vincent [Univ. of Paris (France); de Lamballerie, Xavier [Aix-Marseille Univ. (France); L, So-Yonim [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Osuna, Christa E [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Whitney, James [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Perelson, Alan S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-10-24

    The recent outbreak of Zika virus (ZIKV) has been associated with fetal abnormalities and neurological complications, prompting global concern. Here we present the first mathematical analysis of the within-host dynamics of plasma ZiKV burden in a non-human primate model, allowing for characterization of the growth and clearance of ZIKV within an individual macaque.

  8. Gastroenteric tube feeding: Techniques, problems and solutions

    National Research Council Canada - National Science Library

    Irina Blumenstein Yogesh M Shastri Jürgen Stein

    2014-01-01

    Gastroenteric tube feeding plays a major role in the management of patients with poor voluntary intake,chronic neurological or mechanical dysphagia or gut dysfunction,and patients who are critically...

  9. Hepatitis B viral core protein disrupts human host gene expression by binding to promoter regions

    Directory of Open Access Journals (Sweden)

    Guo Yanhai

    2012-10-01

    Full Text Available Abstract Background The core protein (HBc of hepatitis B virus (HBV has been implicated in the malignant transformation of chronically-infected hepatocytes and displays pleiotropic functions, including RNA- and DNA-binding activities. However, the mechanism by which HBc interacts with the human genome to exert effects on hepatocyte function remains unknown. This study investigated the distribution of HBc binding to promoters in the human genome and evaluated its effects on the related genes’ expression. Results Whole-genome chromatin immunoprecipitation microarray (ChIP-on-chip analysis was used to identify HBc-bound human gene promoters. Gene Ontology and pathway analyses were performed on related genes. The quantitative polymerase chain reaction assay was used to verify ChIP-on-chip results. Five novel genes were selected for luciferase reporter assay evaluation to assess the influence of HBc promoter binding. The HBc antibody immunoprecipitated approximately 3100 human gene promoters. Among these, 1993 are associated with known biological processes, and 2208 regulate genes with defined molecular functions. In total, 1286 of the related genes mediate primary metabolic processes, and 1398 encode proteins with binding activity. Sixty-four of the promoters regulate genes related to the mitogen-activated protein kinase (MAPK pathways, and 41 regulate Wnt/beta-catenin pathway genes. The reporter gene assay indicated that HBc binding up-regulates proto-oncogene tyrosine-protein kinase (SRC, type 1 insulin-like growth factor receptor (IGF1R, and neurotrophic tyrosine kinase receptor 2 (NTRK2, and down-regulates v-Ha-ras Harvey rat sarcoma viral oncogene (HRAS. Conclusion HBc has the ability to bind a large number of human gene promoters, and can disrupt normal host gene expression. Manipulation of the transcriptional profile in HBV-infected hepatocytes may represent a key pathogenic mechanism of HBV infection.

  10. Benign afebrile cluster convulsions with gastroenteritis: an observational study

    Directory of Open Access Journals (Sweden)

    Narchi Hassib

    2004-02-01

    Full Text Available Abstract Backround The occurrence of afebrile seizures in association with viral gastroenteritis, without dehydration or electrolyte imbalance, is virtually unknown outside Asia. They are reported to have a benign prognosis and not to require specific investigations or therapy. Methods We report the occurrence of such afebrile convulsions in association with viral gastroenteritis without dehydration or electrolyte imbalance, over a 3-year period, in a cohort of 14 British children. Results The children (5 males and 9 females, 10 Caucasians and 4 Asians were aged 9 to 60 months (median 14.5 months. All 14 had a normal neurological examination and normal serum biochemistry. Twelve children had generalised seizures and 2 had, in addition, absence seizures. The number of seizures per child ranged from 1 to 8. Most convulsions were short with 85.7% of children having the longest seizure not longer than 4 minutes. The longest duration for a seizure was 10 minutes and occurred in 2 children. Convulsions did not recur after the first day in 10 children, 3 children had recurrences the second day and one child on the fourth day. No convulsions recurred after 4 days. Cerebrospinal fluid studies, computed tomography and electroencephalogram (EEG were performed on two children who had prolonged seizures and the results were normal. No pathogenic bacteria were grown in any of the stools. Enzyme immunoassay detection of Rotavirus in the stools was positive in 7 of the 10 children where it was tested. All 14 children recovered spontaneously within a few days. On long-term follow of up to 31 months (median 16 months, none had further convulsions and all had normal development milestones. Conclusions Afebrile seizures in association with viral gastroenteritis do also occur outside Asia. Recognition of this entity should lead to reassurance of the parents. As in previously published series, investigations such as lumbar puncture, neuroimaging and EEG are usually

  11. Human T cell aging and the impact of persistent viral infections

    Directory of Open Access Journals (Sweden)

    Tamas eFulop

    2013-09-01

    Full Text Available Aging is associated with a dysregulation of the immune response, loosely termed immunosenescence. Each part of the immune system is influenced to some extent by the aging process. However, adaptive immunity seems more extensively affected and among all participating cells it is the T cells that are most altered. There is a large body of experimental work devoted to the investigation of age-associated differences in T cell phenotypes and functions in young and old individuals, but few longitudinal studies in humans actually delineating changes at the level of the individual. In most studies, the number and proportion of late-differentiated T cells, especially CD8+ T cells, is reported to be higher in the elderly than in the young. Limited longitudinal studies suggest that accumulation of these cells is a dynamic process and does indeed represent an age-associated change. Accumulations of such late-stage cells may contribute to the enhanced systemic pro-inflammatory milieu commonly seen in older people. We do not know exactly what causes these observed changes, but an understanding of the possible causes is now beginning to emerge. A favored hypothesis is that these events are at least partly due to the effects of the maintenance of essential immune surveillance against persistent viral infections, notably Cytomegalovirus (CMV, which may exhaust the immune system over time. It is still a matter of debate as to whether these changes are compensatory and beneficial or pathological and detrimental to the proper functioning of the immune system and whether they impact longevity. Here, we will review present knowledge of T cell changes with aging and their relation to chronic viral and possibly other persistent infections.

  12. Novel Human Cytomegalovirus Viral Chemokines, vCXCL-1s, Display Functional Selectivity for Neutrophil Signaling and Function

    NARCIS (Netherlands)

    Heo, Jinho; Dogra, Pranay; Masi, Tom J; Pitt, Elisabeth A; de Kruijf, Petra; Smit, Martine J; Sparer, Tim E

    2015-01-01

    Human CMV (HCMV) uses members of the hematopoietic system including neutrophils for dissemination throughout the body. HCMV encodes a viral chemokine, vCXCL-1, that is postulated to attract neutrophils for dissemination within the host. The gene encoding vCXCL-1, UL146, is one of the most variable

  13. Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

    Science.gov (United States)

    Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

    2017-06-15

    Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We

  14. Quantitative screening of single copies of human papilloma viral DNA without amplification.

    Science.gov (United States)

    Li, Jiangwei; Lee, Ji-Young; Yeung, Edward S

    2006-09-15

    We describe a novel quantitative viral screening method based on single-molecule detection that does not require amplification. DNA of human papilloma virus (HPV), the major etiological agent of cervical cancer, served as the screening target in this study. Eight 100-nucleotide single-stranded DNA probes were designed complementary to the E6-E7 gene of HPV-16 DNA. The probes were covalently stained with Alexa Fluor 532 and hybridized to the target in solution. The individual hybridized molecules were imaged with an intensified charge-coupled device (ICCD) in two ways. In the single-color mode, target molecules were detected via fluorescence from hybridized probes only. This system could detect HPV-16 DNA in the presence of human genomic DNA down to 0.7 copy/cell and had a linear dynamic range of over 6 orders of magnitude. In the dual-color mode, we employed fluorescence resonance energy transfer and added YOYO-3 dye as the acceptor. The two colors from Alexa Fluor 532 and YOYO-3 were dispersed by a transmission grating located in front of the ICCD. With this reinforced criterion for identifying the hybridized molecules, zero false-positive count was achieved. We also showed that DNA extracts from Pap test specimens did not interfere with the measurements.

  15. Vaccination Reduces Simian-Human Immunodeficiency Virus Sequence Reversion through Enhanced Viral Control▿

    Science.gov (United States)

    Manuel, Edwin R.; Yeh, Wendy W.; Balachandran, Harikrishnan; Clarke, Ryon H.; Lifton, Michelle A.; Letvin, Norman L.

    2010-01-01

    It has been suggested that vaccination prior to infection may direct the mutational evolution of human immunodeficiency virus type 1 (HIV-1) to a less fit virus, resulting in an attenuated course of disease. The present study was initiated to explore whether prior immunization might prevent the reversion of the virus to the wild-type form. Mamu-A*01 monkeys were vaccinated to generate a cytotoxic T-lymphocyte response to the immunodominant Gag p11C epitope and were then challenged with a cloned pathogenic CXCR4-tropic simian-human immunodeficiency virus (SHIV) expressing a mutant Gag p11C sequence (Δp11C SHIV). The epitopic and extraepitopic compensatory mutations introduced into gag of Δp11C SHIV resulted in attenuated replicative capacity and eventual reversions to the wild-type Gag p11C sequence in naïve rhesus monkeys. However, in vaccinated rhesus monkeys, no reversions of the challenge virus were observed, an effect that may have been a consequence of significantly decreased viral replication rather than a redirection of the mutational evolution of the virus. These findings highlight the multifactorial pressures that affect the evolution of primate immunodeficiency viruses. PMID:20881040

  16. Vaccination reduces simian-human immunodeficiency virus sequence reversion through enhanced viral control.

    Science.gov (United States)

    Manuel, Edwin R; Yeh, Wendy W; Balachandran, Harikrishnan; Clarke, Ryon H; Lifton, Michelle A; Letvin, Norman L

    2010-12-01

    It has been suggested that vaccination prior to infection may direct the mutational evolution of human immunodeficiency virus type 1 (HIV-1) to a less fit virus, resulting in an attenuated course of disease. The present study was initiated to explore whether prior immunization might prevent the reversion of the virus to the wild-type form. Mamu-A*01 monkeys were vaccinated to generate a cytotoxic T-lymphocyte response to the immunodominant Gag p11C epitope and were then challenged with a cloned pathogenic CXCR4-tropic simian-human immunodeficiency virus (SHIV) expressing a mutant Gag p11C sequence (Δp11C SHIV). The epitopic and extraepitopic compensatory mutations introduced into gag of Δp11C SHIV resulted in attenuated replicative capacity and eventual reversions to the wild-type Gag p11C sequence in naïve rhesus monkeys. However, in vaccinated rhesus monkeys, no reversions of the challenge virus were observed, an effect that may have been a consequence of significantly decreased viral replication rather than a redirection of the mutational evolution of the virus. These findings highlight the multifactorial pressures that affect the evolution of primate immunodeficiency viruses.

  17. Internalization of novel non-viral vector TAT-streptavidin into human cells

    Directory of Open Access Journals (Sweden)

    Kulomaa Markku S

    2007-01-01

    Full Text Available Abstract Background The cell-penetrating peptide derived from the Human immunodeficiency virus-1 transactivator protein Tat possesses the capacity to promote the effective uptake of various cargo molecules across the plasma membrane in vitro and in vivo. The objective of this study was to characterize the uptake and delivery mechanisms of a novel streptavidin fusion construct, TAT47–57-streptavidin (TAT-SA, 60 kD. SA represents a potentially useful TAT-fusion partner due to its ability to perform as a versatile intracellular delivery vector for a wide array of biotinylated molecules or cargoes. Results By confocal and immunoelectron microscopy the majority of internalized TAT-SA was shown to accumulate in perinuclear vesicles in both cancer and non-cancer cell lines. The uptake studies in living cells with various fluorescent endocytic markers and inhibiting agents suggested that TAT-SA is internalized into cells efficiently, using both clathrin-mediated endocytosis and lipid-raft-mediated macropinocytosis. When endosomal release of TAT-SA was enhanced through the incorporation of a biotinylated, pH-responsive polymer poly(propylacrylic acid (PPAA, nuclear localization of TAT-SA and TAT-SA bound to biotin was markedly improved. Additionally, no significant cytotoxicity was detected in the TAT-SA constructs. Conclusion This study demonstrates that TAT-SA-PPAA is a potential non-viral vector to be utilized in protein therapeutics to deliver biotinylated molecules both into cytoplasm and nucleus of human cells.

  18. Viral Skin Diseases.

    Science.gov (United States)

    Ramdass, Priya; Mullick, Sahil; Farber, Harold F

    2015-12-01

    In the vast world of skin diseases, viral skin disorders account for a significant percentage. Most viral skin diseases present with an exanthem (skin rash) and, oftentimes, an accompanying enanthem (lesions involving the mucosal membrane). In this article, the various viral skin diseases are explored, including viral childhood exanthems (measles, rubella, erythema infectiosum, and roseola), herpes viruses (herpes simplex virus, varicella zoster virus, Kaposi sarcoma herpes virus, viral zoonotic infections [orf, monkeypox, ebola, smallpox]), and several other viral skin diseases, such as human papilloma virus, hand, foot, and mouth disease, molluscum contagiosum, and Gianotti-Crosti syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. High-risk human papillomavirus viral load and persistence among heterosexual HIV-negative and HIV-positive men.

    Science.gov (United States)

    Grabowski, Mary K; Gray, Ronald H; Serwadda, David; Kigozi, Godfrey; Gravitt, Patti E; Nalugoda, Fred; Reynolds, Steven J; Wawer, Maria J; Watya, Stephen; Quinn, Thomas C; Tobian, Aaron A R

    2014-06-01

    High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-HPV persistence in women. It is unknown whether HR-HPV viral load is associated with persistence in HIV-negative or HIV-positive men. HR-HPV viral load and persistence were evaluated among 703 HIV-negative and 233 HIV-positive heterosexual men who participated in a male circumcision trial in Rakai, Uganda. Penile swabs were tested at baseline and 6, 12 and 24 months for HR-HPV using the Roche HPV Linear Array, which provides a semiquantitative measure of HPV shedding by hybridisation band intensity (graded: 1-4). Prevalence risk ratios (PRR) were used to estimate the association between HR-HPV viral load and persistent detection of HR-HPV. HR-HPV genotypes with high viral load (grade:3-4) at baseline were more likely to persist than HR-HPV genotypes with low viral load (grade: 1-2) among HIV-negative men (month 6: adjPRR=1.83, 95% CI 1.32 to 2.52; month 12: adjPRR=2.01, 95% CI 1.42 to 3.11), and HIV-positive men (month 6: adjPRR=1.33, 95% CI 1.06 to 1.67; month 12: adjPRR=1.73, 95% CI 1.18 to 2.54). Long-term persistence of HR-HPV was more frequent among HIV-positive men compared with HIV-negative men (month 24: adjPRR=2.27, 95% CI 1.47 to 3.51). Persistence of newly detected HR-HPV at the 6-month and 12-month visits with high viral load were also more likely to persist to 24 months than HR-HPV with low viral load among HIV-negative men (adjPRR=1.67, 95% CI 0.88 to 3.16). HR-HPV genotypes with high viral load are more likely to persist among HIV-negative and HIV-positive men, though persistence was more common among HIV-positive men overall. The results may explain the association between high HR-HPV viral load and HR-HPV transmission. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Human papillomavirus 16/18 E7 viral loads predict distant metastasis in oral cavity squamous cell carcinoma.

    Science.gov (United States)

    Huang, Chung-Guei; Lee, Li-Ang; Tsao, Kuo-Chien; Liao, Chun-Ta; Yang, Lan-Yan; Kang, Chung-Jan; Chang, Kei-Ping; Huang, Shiang-Fu; Chen, I-How; Yang, Shu-Li; Lee, Li-Yu; Hsueh, Chuen; Chen, Tse-Ching; Lin, Chien-Yu; Fan, Kang-Hsing; Chang, Tung-Chieh; Wang, Hung-Ming; Ng, Shu-Hang; Yen, Tzu-Chen

    2014-10-01

    Human papillomaviruses (HPV) seem to be related to distant metastasis (DM) in advanced oral cavity squamous cell carcinoma (OSCC) patients. This study aimed to investigate whether high-risk HPV viral load may predict DM among OSCC patients and stratify patients for risk-adapted treatment. Viral loads of E7 oncogenes for HPV 16/18 were measured by quantitative PCR tests in paraffin-embedded lesional specimens from 312 OSCC of which the HPV genotypes had been determined previously. Multivariable Cox regression analysis was used to identify the independent prognostic factors for 5-year DM and C statistics were further computed. By multivariable analysis, high HPV 16 E7 viral load (≥15.0 copies/genome); high HPV 18 E7 viral load (≥15.0 copies/genome); pathological N2 status (pN2); tumor depth ≥11 mm; extracapsular spread (ECS); and level IV/V metastases were independent risk factors for DM. We further identified three prognostic groups. In the high-risk group (level IV/V metastases or high HPV 16/18 E7 viral load plus pN2, tumor depth ≥11 mm, or ECS), the 5-year distant metastasis rate was 74%. In the intermediate-risk group (high HPV 16/18 E7 viral load, pN2, tumor depth ≥11 mm, or ECS), the 5-year DM rate was 17%. Finally, the 5-year DM rate was 1% in the low-risk group (no risk factors). The value of the C statistics was 0.78. Among OSCC patients, high HPV 16/18 E7 viral load identifies a small subgroup of patients at high-risk of 5-year DM and suggest the need for more intensive treatments and follow-up strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Modulation of the Host Environment by Human Cytomegalovirus with Viral Interleukin 10 in Peripheral Blood.

    Science.gov (United States)

    Young, Vivian P; Mariano, Margarette C; Tu, Carolyn C; Allaire, Kathryn M; Avdic, Selmir; Slobedman, Barry; Spencer, Juliet V

    2017-03-15

    Human cytomegalovirus (HCMV) is a herpesvirus with both lytic and latent life cycles. Human cytomegalovirus encodes 2 viral cytokines that are orthologs of human cellular interleukin 10 (cIL-10). Both cytomegalovirus interleukin 10 (cmvIL-10) and Latency-associated cytomegalovirus interleukin 10 (LAcmvIL-10) (collectively vIL-10) are expressed during lytic infection and cause immunosuppressive effects that impede virus clearance. LAcmvIL-10 is also expressed during latent infection of myeloid progenitor cells and monocytes and facilitates persistence. Here, we investigated whether vIL-10 could be detected during natural infection. Plasma from healthy blood donors was tested by enzyme-linked immunosorbent assay for anti-HCMV immunoglobulin G and immunoglobulin M and for cIL-10 and vIL-10 levels using a novel vIL-10 assay that detects cmvIL-10 and LAcmvIL-10, with no cross-reactivity to cIL-10. vIL-10 was evident in HCMV+ donors (n = 19 of 26), at levels ranging 31-547 pg/mL. By comparison, cIL-10 was detected at lower levels ranging 3-69 pg/mL. There was a strong correlation between vIL-10 and cIL-10 levels (P = .01). Antibodies against vIL-10 were also detected and neutralized vIL-10 activity. vIL-10 was detected in peripheral blood of healthy blood donors. These findings suggest that vIL-10 may play a key role in sensing or modifying the host environment during latency and, therefore, may be a potential target for intervention strategies.

  2. Molecular biology of human herpesvirus 8: novel functions and virus-host interactions implicated in viral pathogenesis and replication.

    Science.gov (United States)

    Cousins, Emily; Nicholas, John

    2014-01-01

    Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the second identified human gammaherpesvirus. Like its relative Epstein-Barr virus, HHV-8 is linked to B-cell tumors, specifically primary effusion lymphoma and multicentric Castleman's disease, in addition to endothelial-derived KS. HHV-8 is unusual in its possession of a plethora of "accessory" genes and encoded proteins in addition to the core, conserved herpesvirus and gammaherpesvirus genes that are necessary for basic biological functions of these viruses. The HHV-8 accessory proteins specify not only activities deducible from their cellular protein homologies but also novel, unsuspected activities that have revealed new mechanisms of virus-host interaction that serve virus replication or latency and may contribute to the development and progression of virus-associated neoplasia. These proteins include viral interleukin-6 (vIL-6), viral chemokines (vCCLs), viral G protein-coupled receptor (vGPCR), viral interferon regulatory factors (vIRFs), and viral antiapoptotic proteins homologous to FLICE (FADD-like IL-1β converting enzyme)-inhibitory protein (FLIP) and survivin. Other HHV-8 proteins, such as signaling membrane receptors encoded by open reading frames K1 and K15, also interact with host mechanisms in unique ways and have been implicated in viral pathogenesis. Additionally, a set of micro-RNAs encoded by HHV-8 appear to modulate expression of multiple host proteins to provide conditions conducive to virus persistence within the host and could also contribute to HHV-8-induced neoplasia. Here, we review the molecular biology underlying these novel virus-host interactions and their potential roles in both virus biology and virus-associated disease.

  3. Human T-lymphotropic virus type 1–associated myelopathy/tropical spastic paraparesis: Viral load and muscle tone are correlated

    Science.gov (United States)

    Zunt, JR; Montano, SM; Beck, I; Alarcón, JOV; Frenkel, LM; Bautista, CT; Price, R; Longstreth, WT

    2009-01-01

    Human T-lymphotropic virus type 1 (HTLV-1) infections are associated with varying degrees of HTLV-1 viral load and spasticity. Increased viral load is associated with higher risk of developing HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP). The authors performed a cross-sectional study of 24 people with HAM/TSP in Lima, Perú, to determine if higher HTLV-1 viral load was correlated with increased muscle tone, measured with a device providing quantitative spasticity assessment (QSA). Median HTLV-1 viral load was 17.0 copies/100 peripheral blood mononuclear cells and QSA value was 39.9 Newton-meters/radian. HTLV-1 viral load was significantly correlated with QSA value (Spearman rho = .48, P = .02), suggesting viral load may play a role in expression of symptomatic neurologic disease. Longitudinal studies are needed to determine if treatments that reduce viral load will reduce muscle tone. PMID:17162662

  4. Optical manipulation of a single human virus for study of viral-cell interactions.

    Science.gov (United States)

    Hou, Ximiao; DeSantis, Michael C; Tian, Chunjuan; Cheng, Wei

    2016-08-01

    Although Ashkin and Dziedzic first demonstrated optical trapping of individual tobacco mosaic viruses in suspension as early as 1987, this pioneering work has not been followed up only until recently. Using human immunodeficiency virus type 1 (HIV-1) as a model virus, we have recently demonstrated that a single HIV-1 virion can be stabled trapped, manipulated and measured in physiological media with high precision. The capability to optically trap a single virion in suspension not only allows us to determine, for the first time, the refractive index of a single virus with high precision, but also quantitate the heterogeneity among individual virions with single-molecule resolution, the results of which shed light on the molecular mechanisms of virion infectivity. Here we report the further development of a set of microscopic techniques to physically deliver a single HIV-1 virion to a single host cell in solution. Combined with simultaneous epifluorescence imaging, the attachment and dissociation events of individual manipulated virions on host cell surface can be measured and the results help us understand the role of diffusion in mediating viral attachment to host cells. The establishment of these techniques opens up new ways for investigation of a wide range of virion-cell interactions, and should be applicable for study of B cell interactions with particulate antigens such as viruses.

  5. Human herpesvirus 8-associated neoplasms: the roles of viral replication and antiviral treatment.

    Science.gov (United States)

    Gantt, Soren; Casper, Corey

    2011-08-01

    In this review, we highlight the importance of human herpesvirus 8 (HHV-8) lytic replication and the potential for antiviral therapies to prevent or treat HHV-8-related neoplasms. Diseases caused by HHV-8 infection include Kaposi sarcoma, multicentric Castleman disease (MCD), and primary effusion lymphoma (PEL), which occur primarily in patients with HIV infection. Kaposi sarcoma is the most common AIDS-associated malignancy worldwide. MCD and PEL occur less commonly but, like Kaposi sarcoma, are associated with poor treatment outcomes. Like all herpesviruses, HHV-8 is capable of either latent or lytic infection of cells. Although HHV-8 infection of tumor cells is predominately latent, accumulating data point to the importance of both lytic phase viral gene products and production of infectious virus. Antiviral agents that target herpesvirus DNA synthesis, such as ganciclovir, inhibit HHV-8 lytic replication and can prevent Kaposi sarcoma. Several HIV protease inhibitors may interfere with tumor growth and angiogenesis, and one protease inhibitor, nelfinavir, directly inhibits HHV-8 replication in vitro. Controlled trials are indicated to determine the clinical utility of antiviral suppression of HHV-8 replication, and identify the optimal antiretroviral regimens, for the prevention and treatment of Kaposi sarcoma.

  6. Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Lu Chen

    2014-06-01

    Full Text Available Using a viral model of the demyelinating disease multiple sclerosis (MS, we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.

  7. The significance of serum and fecal levels of interleukin-6 and interleukin-8 in hospitalized children with acute rotavirus and norovirus gastroenteritis.

    Science.gov (United States)

    Chen, Shan-Ming; Lin, Ching-Pin; Tsai, Jeng-Dau; Chao, Yu-Hua; Sheu, Ji-Nan

    2014-04-01

    Rotavirus and norovirus are the most common known causes of viral gastroenteritis in children. This study examined the association between serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels and disease severity in the acute phase of rotavirus and norovirus gastroenteritis in children, and it also explored the role of fecal cytokine levels in children with viral and bacterial gastroenteritis. This prospective study enrolled patients aged 4 months to 14 years admitted with acute gastroenteritis in a tertiary care center. Peripheral blood samples were collected for IL-6 and IL-8 assays within the first 3 days of diarrhea. Stool samples were obtained from the patients in the first 24 hours after admission. Serum IL-6 and IL-8 were measured in children with viral (n = 66) and bacterial (n = 23) infections, and in healthy controls (n = 10). In the acute phase of gastroenteritis, a moderately positive correlation was found between serum IL-6 levels and disease severity (rs = 0.41, p fever (rs = 0.28, p = 0.03). Fecal IL-6 levels correlated with the maximum number of daily bowel movements (rs = 0.35, p Rotavirus infection induced significantly higher serum IL-8 levels than norovirus infection (p rotavirus from norovirus gastroenteritis. IL-6 and IL-8 are involved in the pathogenesis of acute gastroenteritis in both rotavirus and norovirus. An ANC of less than 9000/mm(3), maximum BT of less than 38.2°C, and Vesikari score of less than 14 at the end of the course are potential predictors of norovirus infection in children compared with rotavirus gastroenteritis. Copyright © 2013. Published by Elsevier B.V.

  8. Prevalence and evaluation strategies for viral contamination in food products: Risk to human health-a review.

    Science.gov (United States)

    Shukla, Shruti; Cho, Hyunjeong; Kwon, O Jun; Chung, Soo Hyun; Kim, Myunghee

    2018-02-11

    Nowadays, viruses of foodborne origin such as norovirus and hepatitis A are considered major causes of foodborne gastrointestinal illness with widespread distribution worldwide. A number of foodborne outbreaks associated with food products of animal and non-animal origins, which often involve multiple cases of variety of food streams, have been reported. Although several viruses, including rotavirus, adenovirus, astrovirus, parvovirus, and other enteroviruses, significantly contribute to incidence of gastrointestinal diseases, systematic information on the role of food in transmitting such viruses is limited. Most of the outbreak cases caused by infected food handlers were the source of 53% of total outbreaks. Therefore, prevention and hygiene measures to reduce the frequency of foodborne virus outbreaks should focus on food workers and production site of food products. Pivotal strategies, such as proper investigation, surveillance, and reports on foodborne viral illnesses, are needed in order to develop more accurate measures to detect the presence and pathogenesis of viral infection with detailed descriptions. Moreover, molecular epidemiology and surveillance of food samples may help analysis of public health hazards associated with exposure to foodborne viruses. In this present review, we discuss different aspects of foodborne viral contamination and its impact on human health. This review also aims to improve understanding of foodborne viral infections as major causes of human illness as well as provide descriptions of their control and prevention strategies and rapid detection by advanced molecular techniques. Further, a brief description of methods available for the detection of viruses in food and related matrices is provided.

  9. [Methods for the detection of viral contamination in food of animal origin].

    Science.gov (United States)

    Greiser-Wilke, I; Fries, R

    1994-07-01

    Contamination of foods of animal origin with pathogenic human viruses may occur during handling or through polluted water. Most of these viruses are pathogens originating from the human gastrointestinal tract. They can be transmitted by the consumption of contaminated food and often cause disease. A survey is given of DNA- and RNA-viruses that may occur as contaminants of foods. In addition, the classical methods for detecting viral contaminations in foods are summarized. They are based on the effects after virus inoculation of cell cultures. Besides the fact that these methods are not economic and time consuming, they do not permit detection of some of the most important foodborne gastroenteritis viruses. The possibility of replacing these methods by detecting the viral genomes using hybridization and polymerase chain reaction (PCR) is discussed.

  10. Adenovirus, calicivirus and astrovirus detection in fecal samples of hospitalized children with acute gastroenteritis from Campo Grande, MS, Brazil

    Directory of Open Access Journals (Sweden)

    Marcia Sueli Assis Andreasi

    2008-11-01

    Full Text Available We analyzed fecal samples from hospitalized children up to three years of age with acute gastroenteritis at Campo Grande, Mato Grosso do Sul, Brazil, from May 2000-January 2004. Astrovirus and calicivirus were detected by Reverse Transcription-Polymerase Chain Reaction and adenovirus was detected using the Rotavirus and Adenovirus combined immunoenzyme assay. Astrovirus, adenovirus and calicivirus were detected at rates of 3.1%, 3.6% and 7.6%, respectively. These results re-emphasize the need for the establishment of regional vigilance systems to evaluate the impact of enteric viruses on viral gastroenteritis.

  11. Acute gastroenteritis: from guidelines to real life

    Directory of Open Access Journals (Sweden)

    Chung M Chow

    2010-07-01

    Full Text Available Chung M Chow1, Alexander KC Leung2, Kam L Hon11Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, PR China; 2Department of Pediatrics, The University of Calgary, Calgary, Alberta, CanadaAbstract: Acute gastroenteritis is a very common disease. It causes significant mortality in developing countries and significant economic burden to developed countries. Viruses are ­responsible for approximately 70% of episodes of acute gastroenteritis in children and rotavirus is one of the best studied of these viruses. Oral rehydration therapy is as effective as i­ntravenous therapy in treating mild to moderate dehydration in acute gastroenteritis and is strongly r­ecommended as the first line therapy. However, the oral rehydration solution is described as an underused simple solution. Vomiting is one of the main reasons to explain the underuse of oral rehydration therapy. Antiemetics are not routinely recommended in treating acute gastroenteritis, though they are still commonly prescribed. Ondansetron is one of the best studied antiemetics and its role in enhancing the compliance of oral rehydration therapy and decreasing the rate of hospitalization has been proved recently. The guidelines regarding the recommendation on antiemetics have been changed according to the evidence of these recent studies.Keywords: gastroenteritis, vomiting, antiemetic, ondansetron, rotavirus, oral rehydration therapy, intravenous therapy, guideline

  12. [Relationship between viral load of human bocavirus and clinical characteristics in children with acute lower respiratory tract infection].

    Science.gov (United States)

    Ding, Xiao-Fang; Zhang, Bing; Zhong, Li-Li; Xie, Le-Yun; Xiao, Ni-Guang

    2017-03-01

    To investigate the prevalence of human bocavirus (HBoV) in children with acute lower respiratory tract infection and to explore the relationship between the viral load of HBoV and the clinical characteristics of acute lower respiratory tract infection in children. A total of 1 554 nasopharyngeal aspirates from children who were hospitalized due to acute lower respiratory tract infection between March 2011 and March 2014 were collected. Quantitative real-time PCR was used to detect 12 RNA and 2 DNA viruses, adenovirus (ADV) and HBoV, and to measure the viral load of HBoV in HBoV-positive children. A comprehensive analysis was performed with reference to clinical symptoms and indicators. In the 1 554 specimens, 1 212 (77.99%) were positive for viruses, and 275 (17.70%) were HBoV-positive. In HBoV-positive cases, 94.9% were aged infection, and 230 (83.64%) had mixed infection. There was no significant difference in viral load between children with single infection and mixed infection (P>0.05). The patients with fever had a significantly higher viral load than those without fever (Pacute lower respiratory tract infection (P>0.05). HBoV is one of the important pathogens of acute lower respiratory tract infection in children. Children with a higher viral load of HBoV are more likely to experience symptoms such as fever and wheezing. However, the severity of disease and mixed infection are not significantly related to viral load.

  13. Acute gastroenteritis outbreak associated to norovirus GI.9 in a Portuguese army base.

    Science.gov (United States)

    Lopes-João, António; Mesquita, João R; de Sousa, Rita; Oleastro, Mónica; Penha-Gonçalves, Carlos; Nascimento, Maria Sao José

    2017-05-01

    Gastroenteritis is considered a major illness within the military settings being caused by foodborne enteric pathogens that are particularly easily spread in the crowded conditions of military camps. Gastroenteritis outbreaks caused by norovirus usually affect a great number of soldiers due to the low infectious dose, copious viral shedding, and environmental stability. The present study describes the investigation of an outbreak of acute gastroenteritis that occurred in April 2015 in a Portuguese army base, focusing on the study of the epidemiological curve, symptoms experienced by the affected soldiers, and results of food, water, and stool microbiological analysis. From a total of 938 military personnel stationed on the base 46 soldiers developed acute gastroenteritis. Stool analysis of seven cases showed to be positive for norovirus GI.9 that was the probable cause of the outbreak. This report shows that genogroup I norovirus can also cause considerable morbidity in healthy young soldiers, affecting the operational effectiveness on the military forces. J. Med. Virol. 89:922-925, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Physical status and viral load in women with positive human papillomavirus (HPV) infection in uterine cervix

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    Kim, Byoung Gie; Lee, Eui Don; Zin, Yong Jae [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    This study was performed to determine the frequency of viral integration and viral load in women with positive HPV type 16 infection, and showing normal findings, CIN, and cervical cancer. Total 75 (normal, 15; CIN I, 20; CIN III, 20; cervical cancer, 20) cervical swab specimens were used. HPV detection, typing, and viral load was determined by PCR method. Seventy of 75 (93.3%) of cervical swab specimens showed same results with hybrid capture assay and PCR method for detecting HPV DNA. HPV type 16 DNA was identified more frequently with progression from normal to cervical cancer (normal, 13 %; CIN I, 15%; CIN III, 40 %; cervical cancer, 55 %). The frequency of HPV type 16 DNA integration also increased with grade of the lesion (normal, 0 %; CIN I, 33 %; CIN III, 87 %; cervical cancer, 91 %) suggesting most of HPV type 16 present as integration forms in the cells. In addition, high-level of HPV 16 viral load also was found more frequently in CIN III and cervical cancer (normal, 0 %; CIN I, 0 %; CIN III, 87 %; cervical cancer, 100 %). These results suggest that viral integration and high-level of viral load may play an important role in cervical carcinogenesis. (author). 13 refs., 5 figs.

  15. Viral DNA Replication Orientation and hnRNPs Regulate Transcription of the Human Papillomavirus 18 Late Promoter.

    Science.gov (United States)

    Wang, Xiaohong; Liu, Haibin; Ge, Hui; Ajiro, Masahiko; Sharma, Nishi R; Meyers, Craig; Morozov, Pavel; Tuschl, Thomas; Klar, Amar; Court, Donald; Zheng, Zhi-Ming

    2017-05-30

    The life cycle of human papillomaviruses (HPVs) is tightly linked to keratinocyte differentiation. Although expression of viral early genes is initiated immediately upon virus infection of undifferentiated basal cells, viral DNA amplification and late gene expression occur only in the mid to upper strata of the keratinocytes undergoing terminal differentiation. In this report, we show that the relative activity of HPV18 TATA-less late promoter P811 depends on its orientation relative to that of the origin (Ori) of viral DNA replication and is sensitive to the eukaryotic DNA polymerase inhibitor aphidicolin. Additionally, transfected 70-nucleotide (nt)-long single-strand DNA oligonucleotides that are homologous to the region near Ori induce late promoter activity. We also found that promoter activation in raft cultures leads to production of the late promoter-associated, sense-strand transcription initiation RNAs (tiRNAs) and splice-site small RNAs (spliRNAs). Finally, a cis-acting AAGTATGCA core element that functions as a repressor to the promoter was identified. This element interacts with hnRNP D0B and hnRNP A/B factors. Point mutations in the core prevented binding of hnRNPs and increased the promoter activity. Confirming this result, knocking down the expression of both hnRNPs in keratinocytes led to increased promoter activity. Taking the data together, our study revealed the mechanism of how the HPV18 late promoter is regulated by DNA replication and host factors.IMPORTANCE It has been known for decades that the activity of viral late promoters is associated with viral DNA replication among almost all DNA viruses. However, the mechanism of how DNA replication activates the viral late promoter and what components of the replication machinery are involved remain largely unknown. In this study, we characterized the P811 promoter region of HPV18 and demonstrated that its activation depends on the orientation of DNA replication. Using single

  16. Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To Limit Essential Viral Functions.

    Science.gov (United States)

    Freudenberger, Nora; Meyer, Tina; Groitl, Peter; Dobner, Thomas; Schreiner, Sabrina

    2018-02-15

    Human adenoviruses (HAdV) are nonenveloped viruses containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear pore complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was poorly understood. The core protein V is speculated to bridge the core and the surrounding capsid. It binds the genome in a sequence-independent manner and localizes in the nucleus of infected cells, accumulating at nucleoli. Here, we show that protein V contains conserved SUMO conjugation motifs (SCMs). Mutation of these consensus motifs resulted in reduced SUMOylation of the protein; thus, protein V represents a novel target of the host SUMOylation machinery. To understand the role of protein V SUMO posttranslational modification during productive HAdV infection, we generated a replication-competent HAdV with SCM mutations within the protein V coding sequence. Phenotypic analyses revealed that these SCM mutations are beneficial for adenoviral replication. Blocking protein V SUMOylation at specific sites shifts the onset of viral DNA replication to earlier time points during infection and promotes viral gene expression. Simultaneously, the altered kinetics within the viral life cycle are accompanied by more efficient proteasomal degradation of host determinants and increased virus progeny production than that observed during wild-type infection. Taken together, our studies show that protein V SUMOylation reduces virus growth; hence, protein V SUMOylation represents an important novel aspect of the host antiviral strategy to limit virus replication and thereby points to potential intervention strategies. IMPORTANCE Many decades of research have revealed that HAdV structural proteins promote viral entry and mainly physical stability of the viral genome in the capsid. Our work over the last years showed that this

  17. Viral pathogens.

    Science.gov (United States)

    Ragni, M V; Sherman, K E; Jordan, J A

    2010-07-01

    Despite continuous improvement in safety and purity of blood products for individuals with haemophilia, transmissible agents continue to affect individuals with haemophilia. This chapter addresses three viral pathogens with significant clinical impact: HIV, hepatitis C and parvovirus B19. Hepatitis C is the leading cause of chronic hepatitis and the major co-morbid complication of haemophilia treatment. Clinically, asymptomatic intermittent alanine aminotransferase elevation is typical, with biopsy evidence of advanced fibrosis currently in 25%. Current treatment is effective in up to 70%, and many new agents are in development. For those progressing to end-stage liver disease, liver transplantation outcomes are similar to those in non-haemophilia subjects, although pretransplant mortality is higher. HIV infection, the second leading co-morbid condition in haemophilia, is managed as a chronic infection with highly active antiretroviral therapy (HAART). HAART also slows hepatitis C virus (HCV) progression in those with HIV/HCV co-infection. Viral inactivation and recombinant technologies have effectively prevented transfusion-transmitted viral pathogens in haemophilia. Human parvovirus B19 infection, typically associated with anaemia or, rarely severe aplastic crisis, is a non-lipid enveloped virus, for which standard inactivation techniques are ineffective. Thus, nucleic acid testing (NAT) to screen the blood supply for B19 DNA is currently under consideration by the Food and Drug Administration. To the extent, viral inactivation, recombinant, and NAT technologies are available worldwide, and the lifespan for those with haemophilia is approaching that of the normal population. The purpose of this chapter is to provide an update on three clinically significant transfusion-transmitted viral pathogens.

  18. An atypical rotavirus detected in a child with gastroenteritis in Rio de Janeiro, Brazil

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    H. G. Pereira

    1983-09-01

    Full Text Available Particles morphologically identical to rotaviruses were found in the faeces of a nine week-old child with gastroenteritis. Analysis of the viral RNA genome by polyacrylamine gel electrophoresis revealed 10 bands (probably 11 segments some of wich differed in migration rate from those of the great majority of rotaviruses infecting man and other animal hosts. The virus was not detected by a highly sensitive enzyme immunoassay (ELISA and therefore probably lacked the crossreactive antigen(s shared by the majority rotaviruses. This was the only strain with such behaviour among 230 rotaviruses of human origin examined in this laboratory since 1979. The implications of the existence of non-crossreactive rotaviruses are discussed.Partículas morfologicamente idênticas a rotavirus foram encontradas nas fezes de uma criança de dois meses com gastroenterite. Análise do genoma viral por eletroforese em gel de poliacrilamida revelou 10 faixas (provavelmente 11 segmentos de RNA, algumas das quais diferem em velocidade de migração das observadas na grande maioria de rotavirus de hospedeiros humanos e de diversas espécies de animais. O vírus não foi revelado por um ensaio imuno-enzimático de alta sensibilidade, o que sugere a ausência do antígeno de grupo que da reações cruzadas entre a maioria dos rotavirus. O vírus descrito no presente trabalho foi o único com tal comportamento entre 230 amostras analisadas por nós desde 1979. A relevância de existência de rotavirus não relacionados antigenicamente a outros membros do grupo é discutida.

  19. Identification of human viral protein-derived ligands recognized by individual MHCI-restricted T-cell receptors

    Science.gov (United States)

    Szomolay, Barbara; Liu, Jie; Brown, Paul E; Miles, John J; Clement, Mathew; Llewellyn-Lacey, Sian; Dolton, Garry; Ekeruche-Makinde, Julia; Lissina, Anya; Schauenburg, Andrea J; Sewell, Andrew K; Burrows, Scott R; Roederer, Mario; Price, David A; Wooldridge, Linda; van den Berg, Hugo A

    2016-01-01

    Evidence indicates that autoimmunity can be triggered by virus-specific CD8+ T cells that crossreact with self-derived peptide epitopes presented on the cell surface by major histocompatibility complex class I (MHCI) molecules. Identification of the associated viral pathogens is challenging because individual T-cell receptors can potentially recognize up to a million different peptides. Here, we generate peptide length-matched combinatorial peptide library (CPL) scan data for a panel of virus-specific CD8+ T-cell clones spanning different restriction elements and a range of epitope lengths. CPL scan data drove a protein database search limited to viruses that infect humans. Peptide sequences were ranked in order of likelihood of recognition. For all anti-viral CD8+ T-cell clones examined in this study, the index peptide was either the top-ranked sequence or ranked as one of the most likely sequences to be recognized. Thus, we demonstrate that anti-viral CD8+ T-cell clones are highly focused on their index peptide sequence and that ‘CPL-driven database searching' can be used to identify the inciting virus-derived epitope for a given CD8+ T-cell clone. Moreover, to augment access to CPL-driven database searching, we have created a publicly accessible webtool. Application of these methodologies in the clinical setting may clarify the role of viral pathogens in the etiology of autoimmune diseases. PMID:26846725

  20. Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease.

    Science.gov (United States)

    Moe, Nina; Krokstad, Sidsel; Stenseng, Inger Heimdal; Christensen, Andreas; Skanke, Lars Høsøien; Risnes, Kari Ravndal; Nordbø, Svein Arne; Døllner, Henrik

    2017-01-01

    It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV). We prospectively enrolled hospitalized children aged disease severity among single virus-infected children, where children disease than those with RSV, while in children 12-23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. Among hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children.

  1. Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress Complex and the Viral Protein Kinase pUL97.

    Science.gov (United States)

    Milbradt, Jens; Sonntag, Eric; Wagner, Sabrina; Strojan, Hanife; Wangen, Christina; Lenac Rovis, Tihana; Lisnic, Berislav; Jonjic, Stipan; Sticht, Heinrich; Britt, William J; Schlötzer-Schrehardt, Ursula; Marschall, Manfred

    2018-01-13

    The nuclear phase of herpesvirus replication is regulated through the formation of regulatory multi-component protein complexes. Viral genomic replication is followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The latter has been studied intensely pointing to the formation of a viral core nuclear egress complex (NEC) that recruits a multimeric assembly of viral and cellular factors for the reorganization of the nuclear envelope. To date, the mechanism of the association of human cytomegalovirus (HCMV) capsids with the NEC, which in turn initiates the specific steps of nuclear capsid budding, remains undefined. Here, we provide electron microscopy-based data demonstrating the association of both nuclear capsids and NEC proteins at nuclear lamina budding sites. Specifically, immunogold labelling of the core NEC constituent pUL53 and NEC-associated viral kinase pUL97 suggested an intranuclear NEC-capsid interaction. Staining patterns with phospho-specific lamin A/C antibodies are compatible with earlier postulates of targeted capsid egress at lamina-depleted areas. Important data were provided by co-immunoprecipitation and in vitro kinase analyses using lysates from HCMV-infected cells, nuclear fractions, or infectious virions. Data strongly suggest that nuclear capsids interact with pUL53 and pUL97. Combined, the findings support a refined concept of HCMV nuclear trafficking and NEC-capsid interaction.

  2. High viral load in lymph nodes and latent human immunodeficiency virus (HIV) in peripheral blood cells of HIV-1-infected chimpanzees.

    OpenAIRE

    Saksela, K; Muchmore, E; Girard, M; Fultz, P; Baltimore, D

    1993-01-01

    We have examined human immunodeficiency virus type 1 (HIV-1) infection in chimpanzees by analyzing HIV-1 DNA and RNA in lymph nodes and peripheral mononuclear cells (PBMCs). Like certain asymptomatic HIV-infected persons, these chimpanzees had no detectable viral replication in their PBMCs. However, viral replication and a high viral load were observed in the lymphatic tissue. Despite the absence of viral replication in PBMCs, 1/1,000 to 1/10,000 of the PBMCs contained HIV-1 proviral DNA, and...

  3. Viral Causes of Lymphoma: The History of Epstein-Barr Virus and Human T-Lymphotropic Virus 1

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    Daniel Esau

    2017-09-01

    Full Text Available In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1, human immunodeficiency virus (HIV, Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis. Lymphomas have also played an important role in the history of oncoviruses, as both the first human oncovirus (EBV and the first human retrovirus (HTLV-1 were discovered through isolates taken from patients with unique lymphoma syndromes. The history of the discovery of these 2 key oncoviruses is presented here, and their impact on further medical research, using the specific example of HIV research, is briefly discussed.

  4. Viral Causes of Lymphoma: The History of Epstein-Barr Virus and Human T-Lymphotropic Virus 1.

    Science.gov (United States)

    Esau, Daniel

    2017-01-01

    In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV) was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1), human immunodeficiency virus (HIV), Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis. Lymphomas have also played an important role in the history of oncoviruses, as both the first human oncovirus (EBV) and the first human retrovirus (HTLV-1) were discovered through isolates taken from patients with unique lymphoma syndromes. The history of the discovery of these 2 key oncoviruses is presented here, and their impact on further medical research, using the specific example of HIV research, is briefly discussed.

  5. A humanized mouse-based HIV-1 viral outgrowth assay with higher sensitivity than in vitro qVOA in detecting latently infected cells from individuals on ART with undetectable viral loads.

    Science.gov (United States)

    Charlins, Paige; Schmitt, Kimberly; Remling-Mulder, Leila; Hogan, Louise E; Hanhauser, Emily; Hobbs, Kristen S; Hecht, Frederick; Deeks, Steven G; Henrich, Timothy J; Akkina, Ramesh

    2017-07-01

    Assays that can verify full viral eradication are essential in the context of achieving a cure for HIV/AIDS. In vitro quantitative viral out growth assays (qVOA) are currently the gold standard for measuring latent HIV-1 but these assays often fail to detect very low levels of replication-competent virus. Here we investigated an alternative in vivo approach for sensitive viral detection using humanized mice (hmVOA). Peripheral blood CD4+ T cell samples from HIV subjects on stable ART with undetectable viral loads by RT-PCR were first assayed by in vitro qVOA. Corresponding patient samples in which no virus was detected by qVOA were injected into humanized mice to allow viral outgrowth. Of the five qVOA virus negative samples, four gave positive viral outgrowth in the hmVOA assay suggesting that it is more sensitive in detecting latent HIV-1. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Increased methylation of Human Papillomavirus type 16 DNA correlates with viral integration in Vulval Intraepithelial Neoplasia.

    Science.gov (United States)

    Bryant, Dean; Onions, Tiffany; Raybould, Rachel; Jones, Sadie; Tristram, Amanda; Hibbitts, Samantha; Fiander, Alison; Powell, Ned

    2014-11-01

    Methylation of HPV16 DNA is a promising biomarker for triage of HPV positive cervical screening samples but the biological basis for the association between HPV-associated neoplasia and increased methylation is unclear. To determine whether HPV16 DNA methylation was associated with viral integration, and investigate the relationships between viral DNA methylation, integration and gene expression. HPV16 DNA methylation, integration and gene expression were assessed using pyrosequencing, ligation-mediated PCR and QPCR, in biopsies from 25 patients attending a specialist vulval neoplasia clinic and in short-term clonal cell lines derived from vulval and vaginal neoplasia. Increased methylation of the HPV16 L1/L2 and E2 regions was associated with integration of viral DNA into the host genome. This relationship was observed both in vivo and in vitro. Increased methylation of E2 binding sites did not appear to be associated with greater expression of viral early genes. Expression of HPV E6 and E7 did not correlate with either integration state or increased L1/L2 methylation. The data suggest that increased HPV DNA methylation may be partly attributable to viral integration, and provide a biological rationale for quantification of L1/L2 methylation in triage of HPV positive cervical screening samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Viral Hepatitis

    Science.gov (United States)

    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  8. Gefitinib and pyrrolidine dithiocarbamate decrease viral replication and cytokine production in dengue virus infected human monocyte cultures.

    Science.gov (United States)

    Duran, Anyelo; Valero, Nereida; Mosquera, Jesús; Fuenmayor, Edgard; Alvarez-Mon, Melchor

    2017-12-15

    The epidermal growth factor receptor (EGFR) and nucleotide-binding and oligomerization-domain containing 2 (NOD2) are important in cancer and in microbial recognition, respectively. These molecules trigger intracellular signaling pathways inducing the expression of inflammatory genes by NF-kB translocation. Gefitinib (GBTC) and pyrrolidine dithiocarbamate (PDTC) are capable of inhibiting EGFR/NOD2 and NF-kB, respectively. In earlier stages of dengue virus (DENV) infection, monocytes are capable of sustaining viral replication and increasing cytokine production, suggesting that monocyte/macrophages play an important role in early DENV replication. GBTC and PDTC have not been used to modify the pathogenesis of DENV in infected cells. This study was aimed to determine the effect of GBTC and PDTC on viral replication and cytokine production in DENV serotype 2 (DENV2)-infected human monocyte cultures. GBTC and PDTC were used to inhibit EGFR/NOD2 and NF-kB, respectively. Cytokine production was measured by ELISA and viral replication by plaque forming unit assay. Increased DENV2 replication and anti-viral cytokine production (IFN-α/β, TNF-α, IL-12 and IL-18) in infected cultures were found. These parameters were decreased after EGFR/NOD2 or NF-kB inhibitions. The inhibitory effects of GBTC and PDTC on viral replication and cytokine production can be beneficial in the treatment of patients infected by dengue and suggest a possible role of EGFR/NOD2 receptors and NF-kB in dengue pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. GCN2 has inhibitory effect on human immunodeficiency virus-1 protein synthesis and is cleaved upon viral infection.

    Directory of Open Access Journals (Sweden)

    Javier del Pino

    Full Text Available The reversible phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 (eIF2alpha is a well-characterized mechanism of translational control in response to a wide variety of cellular stresses, including viral infection. Beside PKR, the eIF2alpha kinase GCN2 participates in the cellular response against viral infection by RNA viruses with central nervous system tropism. PKR has also been involved in the antiviral response against HIV-1, although this antiviral effect is very limited due to the distinct mechanisms evolved by the virus to counteract PKR action. Here we report that infection of human cells with HIV-1 conveys the proteolytic cleavage of GCN2 and that purified HIV-1 and HIV-2 proteases produce direct proteolysis of GCN2 in vitro, abrogating the activation of GCN2 by HIV-1 RNA. Transfection of distinct cell lines with a plasmid encoding an HIV-1 cDNA clone competent for a single round of replication resulted in the activation of GCN2 and the subsequent eIF2alpha phosphorylation. Moreover, transfection of GCN2 knockout cells or cells with low levels of phosphorylated eIF2alpha with the same HIV-1 cDNA clone resulted in a marked increase of HIV-1 protein synthesis. Also, the over-expression of GCN2 in cells led to a diminished viral protein synthesis. These findings suggest that viral RNA produced during HIV-1 infection activates GCN2 leading to inhibition of viral RNA translation, and that HIV-1 protease cleaves GCN2 to overcome its antiviral effect.

  10. Impact of cell regeneration in human respiratory tract on simultaneous viral infections

    Science.gov (United States)

    Pinky, Lubna Jahan Rashid; Dobrovolny, Hana

    2015-03-01

    Studies have found that ~ 40% of patients hospitalized with influenza-like illness are infected with at least two different viruses. In these longer infections, we need to consider the role of cell regeneration. Several mathematical models have been used to describe cell regeneration in infection models, though the effect of model choice on the predicted time course of simultaneous viral infections is not clear. We investigate a series of mathematical models of cell regeneration during simultaneous respiratory virus infections to determine the effect of cell regeneration on infection dynamics. We perform a nonlinear stability analysis for each model. The analysis suggests that coexistence of two viral species is not possible for any form of regeneration. We find that chronic illness is possible, but with only one viral species.

  11. Novel microRNA-like viral small regulatory RNAs arising during human hepatitis A virus infection.

    Science.gov (United States)

    Shi, Jiandong; Sun, Jing; Wang, Bin; Wu, Meini; Zhang, Jing; Duan, Zhiqing; Wang, Haixuan; Hu, Ningzhu; Hu, Yunzhang

    2014-10-01

    MicroRNAs (miRNAs), including host miRNAs and viral miRNAs, play vital roles in regulating host-virus interactions. DNA viruses encode miRNAs that regulate the viral life cycle. However, it is generally believed that cytoplasmic RNA viruses do not encode miRNAs, owing to inaccessible cellular miRNA processing machinery. Here, we provide a comprehensive genome-wide analysis and identification of miRNAs that were derived from hepatitis A virus (HAV; Hu/China/H2/1982), which is a typical cytoplasmic RNA virus. Using deep-sequencing and in silico approaches, we identified 2 novel virally encoded miRNAs, named hav-miR-1-5p and hav-miR-2-5p. Both of the novel virally encoded miRNAs were clearly detected in infected cells. Analysis of Dicer enzyme silencing demonstrated that HAV-derived miRNA biogenesis is Dicer dependent. Furthermore, we confirmed that HAV mature miRNAs were generated from viral miRNA precursors (pre-miRNAs) in host cells. Notably, naturally derived HAV miRNAs were biologically and functionally active and induced post-transcriptional gene silencing (PTGS). Genomic location analysis revealed novel miRNAs located in the coding region of the viral genome. Overall, our results show that HAV naturally generates functional miRNA-like small regulatory RNAs during infection. This is the first report of miRNAs derived from the coding region of genomic RNA of a cytoplasmic RNA virus. These observations demonstrate that a cytoplasmic RNA virus can naturally generate functional miRNAs, as DNA viruses do. These findings also contribute to improved understanding of host-RNA virus interactions mediated by RNA virus-derived miRNAs. © FASEB.

  12. Evaluation of extraction methods from paraffin wax embedded tissues for PCR amplification of human and viral DNA.

    Science.gov (United States)

    Chan, P K; Chan, D P; To, K F; Yu, M Y; Cheung, J L; Cheng, A F

    2001-05-01

    To evaluate the efficiency of phenol/chloroform, microwave, and Qiagen spin column based DNA extractions from paraffin wax embedded tissue for use in the polymerase chain reaction (PCR). In addition, to assess the reliability of amplifying a housekeeping gene to indicate successful viral DNA extraction. DNA samples extracted from 20 blocks of cervical carcinoma tissues using the three methods were subjected to PCRs targeting 509 bp and 355 bp of the beta globin gene, and 450 bp and 150 bp of human papillomavirus (HPV) DNA. Microwave extraction showed the highest positive rate for beta globin PCR, whereas the spin column method was the most efficient for HPV DNA extraction. When the 509 bp beta globin and 450 bp HPV PCR results were correlated, two of 10, eight of 12, and nine of 10 beta globin positive extractions prepared by means of the phenol/chloroform, microwave, and spin column methods, respectively, yielded HPV DNA of the expected size. For the beta globin negative samples, HPV was detected in three of 10, two of eight, and four of 10 samples. HPV DNA extraction was most efficient using the Qiagen spin column and had the highest positive predictive value when a housekeeping gene was used as an indicator of successful viral DNA extraction; the phenol/chloroform method was the least efficient. The potential drawbacks of some extraction methods when using a human housekeeping gene to assess the quality of viral DNA extraction need to be considered.

  13. Human β-defensin-2 production upon viral and bacterial co-infection is attenuated in COPD.

    Science.gov (United States)

    Arnason, Jason W; Murphy, James C; Kooi, Cora; Wiehler, Shahina; Traves, Suzanne L; Shelfoon, Christopher; Maciejewski, Barbara; Dumonceaux, Curtis J; Lewenza, W Shawn; Proud, David; Leigh, Richard

    2017-01-01

    Viral-bacterial co-infections are associated with severe exacerbations of COPD. Epithelial antimicrobial peptides, including human β-defensin-2 (HBD-2), are integral to innate host defenses. In this study, we examined how co-infection of airway epithelial cells with rhinovirus and Pseudomonas aeruginosa modulates HBD-2 expression, and whether these responses are attenuated by cigarette smoke and in epithelial cells obtained by bronchial brushings from smokers with normal lung function or from COPD patients. When human airway epithelial cells from normal lungs were infected with rhinovirus, Pseudomonas aeruginosa, or the combination, co-infection with rhinovirus and bacteria resulted in synergistic induction of HBD-2 (peffects of Pseudomonas aeruginosa were mediated via interactions of flagellin with TLR5. The effects of HRV-16 depended upon viral replication but did not appear to be mediated via the intracellular RNA helicases, retinoic acid-inducible gene-I or melanoma differentiation-associated gene-5. Cigarette smoke extract significantly decreased HBD-2 production in response to co-infection. Attenuated production was also observed following co-infection of cells obtained from healthy smokers or COPD patients compared to healthy controls (pexposure to HRV-16 and Pseudomonas aeruginosa induces synergistic production of HBD-2 from epithelial cells and that this synergistic induction of HBD-2 is reduced in COPD patients. This may contribute to the more severe exacerbations these patients experience in response to viral-bacterial co-infections.

  14. Water extract of Cinnamomum cassia Blume inhibited human respiratory syncytial virus by preventing viral attachment, internalization, and syncytium formation.

    Science.gov (United States)

    Yeh, Chia Feng; Chang, Jung San; Wang, Kuo Chih; Shieh, Den En; Chiang, Lien Chai

    2013-05-20

    Cinnamomum cassia Blume is a popular traditional Chinese herbal medicine that has been used to manage respiratory tract disease, including common cold and chronic bronchitis for thousand years. Human respiratory syncytial virus (HRSV) is one of the leading causes of severe lower respiratory tract illness worldwide. No effective therapeutic modality against HRSV infection has been proved. It is unknown whether Cinnamomum cassia is effective against HRSV. This study tested the hypothesis that Cinnamomum cassia can effectively decrease HRSV-induced plaque formation and syncytium formation in respiratory mucosal cell lines. Antiviral activity of the hot water extract of Cinnamomum cassia against HRSV was tested by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines. Its ability to inhibit the synthesis of viral fusion (F) protein was examined by Western blot assay. Cinnamomum cassia dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cell lines (pCinnamomum cassia was more effective when given before viral infection (pCinnamomum cassia could inhibit F protein production and syncytium formation to interfere with HRSV spreading. Cinnamomum cassia prevented airway epithelia from HRSV infection through inhibiting viral attachment, internalization and syncytium formation. Cinnamomum cassia could be a candidate to develop therapeutic modalities to manage HRSV infection in the future. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Molecular analysis of group A rotaviruses detected in adults and adolescents with severe acute gastroenteritis in Italy in 2012.

    Science.gov (United States)

    Ianiro, Giovanni; Delogu, Roberto; Bonomo, Paolo; Fiore, Lucia; Ruggeri, Franco M

    2014-06-01

    Hospital-based surveillance of acute gastroenteritis caused by rotavirus has produced ample knowledge on the infection in children, whereas little is known on rotavirus infection among adults. The Italian surveillance program RotaNet-Italia collected 1,595 samples from patients admitted to hospital with gastroenteritis in 2012. All patients presented with vomiting, diarrhea, fever, and/or abdominal pain. Forty-two samples obtained by the RotaNet-Italia (2.6%) were from adolescents or adults (10-89 years). The study compared the genotypes and gene sequences of the rotavirus strains identified in adults with strains obtained from children worldwide. All 42 Italian strains were genotyped by the EuroRotaNet RT-nested-PCR protocols, and 12 rotaviruses from patients >13-year-old were subjected to nucleotide sequencing of their VP7 and/or VP4 genes. All strains analyzed belonged to the common human genotypes G1P[8], G2P[4], G4P[8], and G9P[8], except an uncommon G3P[19] genotype detected in a single patient. Phylogenetic analysis of the 12 strains showed that within each genotype they clustered in RVA lineages reported worldwide. The amino acid sequences of the VP7 and the VP8* hypervariable regions were highly conserved between the RVA strains collected from adults and children, in each lineage. Genotyping, phylogenetic analysis, and the study of viral epitopes revealed that rotaviruses circulating in adults in Italy are closely similar to the strains circulating in children, with high nucleotide identity particularly with strains reported in Europe and Asia. The circulation of the same rotavirus strains in both children and adults suggests that adults may contribute to sustain the circulation of rotaviruses through the population. © 2014 Wiley Periodicals, Inc.

  16. Neisseria gonorrhoeae co-infection exacerbates vaginal HIV shedding without affecting systemic viral loads in human CD34+ engrafted mice.

    Science.gov (United States)

    Xu, Stacey X; Leontyev, Danila; Kaul, Rupert; Gray-Owen, Scott D

    2018-01-01

    HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.

  17. Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo

    Directory of Open Access Journals (Sweden)

    James M Fox

    2016-03-01

    Full Text Available Clonal expansion of human T-lymphotropic virus type-1 (HTLV-1 infected cells in vivo is well documented. Unlike human immunodeficiency virus type 1 (HIV-1, HTLV-1 plasma RNA is sparse. The contribution of the “mitotic” spread of HTLV-1 compared with infectious spread of the virus to HTLV-1 viral burden in established infection is uncertain. Since extrachromosomal long terminal repeat (LTR DNA circles are indicators of viral replication in HIV-1 carriers with undetectable plasma HIV RNA, we hypothesised that HTLV-1 LTR circles could indicate reverse transcriptase (RT usage and infectious activity. 1LTR and 2LTR DNA circles were measured in HTLV-1 cell lines and peripheral blood mononuclear cells (PBMC of asymptomatic carriers (ACs and patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP or adult T cell leukaemia/lymphoma (ATLL. 1LTR DNA circles were detected in 14/20 patients at a mean of 1.38/100 PBMC but did not differentiate disease status nor correlate with HTLV-1 DNA copies. 2LTR DNA circles were detected in 30/31 patients and at higher concentrations in patients with HTLV-1-associated diseases, independent of HTLV-1 DNA load. In an incident case the 2LTR DNA circle concentration increased 2.1 fold at the onset of HAM/TSP compared to baseline. Detectable and fluctuating levels of HTLV-1 DNA circles in patients indicate viral RT usage and virus replication. Our results indicate HTLV-1 viral replication capacity is maintained in chronic infection and may be associated with disease onset.

  18. Estimating Initial Viral Levels during Simian Immunodeficiency Virus/Human Immunodeficiency Virus Reactivation from Latency

    DEFF Research Database (Denmark)

    Pinkevych, Mykola; Fennessey, Christine M; Cromer, Deborah

    2018-01-01

    the level of detection within a few weeks. There are a number of approaches being tested aimed at either eradicating latently infected cells or controlling the virus if it returns. Studying both the small pool of latently infected cells and the early events during viral reactivation is difficult, because...

  19. INDUCTION OF AUTOANTIBODIES TO HUMAN ENZYMES FOLLOWING VIRAL-INFECTION - A BIOLOGICALLY RELEVANT HYPOTHESIS

    NARCIS (Netherlands)

    WEIJERS, RNM; LAWSON, C; LEUNISSEN, J

    Macro enzymes, i. e. complexes of normal (iso-)enzymes with an immunoglobulin, may be due to immunological cross-reactions evoked by specific viral antigenic determinants that are homologous to regions in the target enzymes. A search of the National Biomedical Research Foundation protein databank

  20. Differences in viral load among human respiratory syncytial virus genotypes in hospitalized children with severe acute respiratory infections in the Philippines.

    Science.gov (United States)

    Kadji, Francois Marie Ngako; Okamoto, Michiko; Furuse, Yuki; Tamaki, Raita; Suzuki, Akira; Lirio, Irene; Dapat, Clyde; Malasao, Rungnapa; Saito, Mariko; Pedrera-Rico, Gay Anne Granada; Tallo, Veronica; Lupisan, Socorro; Saito, Mayuko; Oshitani, Hitoshi

    2016-06-27

    Human respiratory syncytial virus (HRSV) is a leading viral etiologic agent of pediatric lower respiratory infections, including bronchiolitis and pneumonia. Two antigenic subgroups, HRSV-A and B, each contain several genotypes. While viral load may vary among HRSV genotypes and affect the clinical course of disease, data are scarce regarding the actual differences among genotypes. Therefore, this study estimated and compared viral load among NA1 and ON1 genotypes of HRSV-A and BA9 of HRSV-B. ON1 is a newly emerged genotype with a 72-nucleotide duplication in the G gene as observed previously with BA genotypes in HRSV-B. Children <5 years of age with an initial diagnosis of severe or very severe pneumonia at a hospital in the Philippines from September 2012 to December 2013 were enrolled. HRSV genotypes were determined and the viral load measured from nasopharyngeal swabs (NPS). The viral load of HRSV genotype NA1 were significantly higher than those of ON1 and BA9. Regression analysis showed that both genotype NA1 and younger age were significantly associated with high HRSV viral load. The viral load of NA1 was higher than that of ON1 and BA9 in NPS samples. HRSV genotypes may be associated with HRSV viral load. The reasons and clinical impacts of these differences in viral load among HRSV genotypes require further evaluation.

  1. Replication of different clones of human immunodeficiency virus type 1 in primary fetal human astrocytes: enhancement of viral gene expression by Nef.

    Science.gov (United States)

    Bencheikh, M; Bentsman, G; Sarkissian, N; Canki, M; Volsky, D J

    1999-04-01

    Dementia is a common complication of AIDS which is associated with human immunodeficiency virus type 1 (HIV-1) infection of brain macrophages and microglia. Recent studies have shown that astrocytes are also infected in the brain but HIV-1 replication in these cells is restricted. To determine virus specificity of this restriction we tested the expression of 15 HIV-1 molecular clones in primary human fetal astrocytes by infection and DNA transfection. Infection with cell-free viruses was poorly productive and revealed no clone-specific differences. In contrast, transfected cells produced transiently high levels of HIV-1 p24 core antigen, up to 50 nanograms per ml culture supernatant, and nanogram levels of p24 were detected 3-4 weeks after transfection of some viral clones. The average peak expression of HIV-1 in astrocytes varied as a function of viral clone used by a factor of 15 but the differences and the subsequent virus spread did not correlate with the tropism of the viral clones to T cells or macrophages. Functional vif, vpu, and vpr genes were dispensable for virus replication from transfected DNA, but intact nef provided a detectable enhancement of early viral gene expression and promoted maintenance of HIV-1 infection. We conclude that primary astrocytes present no fundamental barriers to moderate expression of different strains of HIV-1 and that the presence of functional Nef is advantageous to virus infection in these cells.

  2. The human adenovirus type 5 E1B 55 kDa protein obstructs inhibition of viral replication by type I interferon in normal human cells.

    Directory of Open Access Journals (Sweden)

    Jasdave S Chahal

    Full Text Available Vectors derived from human adenovirus type 5, which typically lack the E1A and E1B genes, induce robust innate immune responses that limit their therapeutic efficacy. We reported previously that the E1B 55 kDa protein inhibits expression of a set of cellular genes that is highly enriched for those associated with anti-viral defense and immune responses, and includes many interferon-sensitive genes. The sensitivity of replication of E1B 55 kDa null-mutants to exogenous interferon (IFN was therefore examined in normal human fibroblasts and respiratory epithelial cells. Yields of the mutants were reduced at least 500-fold, compared to only 5-fold, for wild-type (WT virus replication. To investigate the mechanistic basis of such inhibition, the accumulation of viral early proteins and genomes was compared by immunoblotting and qPCR, respectively, in WT- and mutant-infected cells in the absence or presence of exogenous IFN. Both the concentration of viral genomes detected during the late phase and the numbers of viral replication centers formed were strongly reduced in IFN-treated cells in the absence of the E1B protein, despite production of similar quantities of viral replication proteins. These defects could not be attributed to degradation of entering viral genomes, induction of apoptosis, or failure to reorganize components of PML nuclear bodies. Nor was assembly of the E1B- and E4 Orf6 protein- E3 ubiquitin ligase required to prevent inhibition of viral replication by IFN. However, by using RT-PCR, the E1B 55 kDa protein was demonstrated to be a potent repressor of expression of IFN-inducible genes in IFN-treated cells. We propose that a primary function of the previously described transcriptional repression activity of the E1B 55 kDa protein is to block expression of IFN- inducible genes, and hence to facilitate formation of viral replication centers and genome replication.

  3. Detection of caliciviruses associated with acute infantile gastroenteritis in Salvador, an urban center in Northeast Brazil

    Directory of Open Access Journals (Sweden)

    M.P.T.P. Xavier

    2009-05-01

    Full Text Available Acute gastroenteritis caused by viruses is one of the leading causes of infantile morbidity. The aim of the present study was to investigate the presence of human caliciviruses of the genera norovirus and sapovirus in children up to 3 years of age with acute gastroenteritis from low-income communities in the city of Salvador, Brazil. This study is an extension of previous work carried out to establish the profile of the most prevalent enteric pathogens present in these communities. In this report, 139 fecal samples, collected from July 2001 to January 2002 were analyzed by RT-PCR and 13 (9% were positive for human caliciviruses. By sequencing, seven isolates were characterized as norovirus genogroup GII and one as sapovirus genotype GII/1. Sequencing of the previously detected group-A rotaviruses and human astroviruses was also performed and revealed the circulation of rotavirus group A genotypes G1P[8] and G9P[8], and human astrovirus genotypes 6, 7, and 8. No mixed infection was observed. Community-based studies provide geographically representative information on disease burden. However, there are only a few reports in developing countries concerning the genotypes of the most important gastroenteric viruses detected in such communities. The present findings demonstrate the wide diversity of genotypes of the most important viruses responsible for acute gastroenteritis circulating in low-income communities.

  4. The landscape of viral proteomics and its potential to impact human health

    Energy Technology Data Exchange (ETDEWEB)

    Oxford, Kristie L.; Wendler, Jason P.; McDermott, Jason E.; White III, Richard A.; Powell, Joshua D.; Jacobs, Jon M.; Adkins, Joshua N.; Waters, Katrina M.

    2016-05-06

    Translating the intimate discourse between viruses and their host cells during infection is a challenging but critical task for development of antiviral interventions and diagnostics. Viruses commandeer cellular processes at every step of their life cycle, altering expression of genes and proteins. Advances in mass spectrometry-based proteomic technologies are enhancing studies of viral pathogenesis by identifying virus-induced changes in the protein repertoire of infected cells or extracellular fluids. Interpretation of proteomics results using knowledge of cellular pathways and networks leads to identification of proteins that influence a range of infection processes, thereby focusing efforts for clinical diagnoses and therapeutics development. Herein we discuss applications of global proteomic studies of viral infections with the goal of providing a basis for improved studies that will benefit community-wide data integration and interpretation.

  5. Viral DNA load of high-risk human papilloma virus is closely associated with the grade of cervical lesions.

    Science.gov (United States)

    Shen, Guqun; Cheng, Jingxin; Wang, Yan; Zhou, Ping; Zhang, Guoqing

    2014-01-01

    This study is to explore the correlation between the viral load of high-risk human papilloma virus (HPV) and the degree of cervical lesions, as well as the follow-up monitoring role of high-risk HPV measurements in the treatment of patients with cervical lesions. Hybrid capture-2 method was used to measure the amount of high-risk HPV load of 361 patients who were enrolled from January 2009 to December 2010 at the Affiliated Tumor Hospital of Xinjiang Medical University, including 76 cases of cervical squamous carcinoma, 119 cases of cervical intraepithelial neoplasia and 166 cases of cervicitis. The correlation between the viral load of high-risk HPV and the degree of cervical lesions was analyzed using correlation analysis. Patients with cervical intraepithelial neoplasia (CIN) and cervical squamous carcinoma were followed up until December 2013, with the follow-up time being 37-60 months. Statistically significant differences in the high-risk HPV load existed between cervicitis group, CIN group and cervical squamous carcinoma group (P = 0.000). In addition, the viral load was increased with the increase of the severity of cervical lesions, showing a positive correlation (r = 0.436, P = 0.000). During the follow-up, 6 cases of vaginal intraepithelial neoplasia, 3 cases of recurrence CIN and 1 case of vaginal squamous cell carcinoma of the vulva were found, which were shown to relate with the continuing high-risk HPV infection in vagina. Viral load of high-risk HPV were positively correlated with the severity of cervical lesions, playing an important role in the monitoring of patients with cervical lesions after treatment.

  6. Human norovirus transmission due to contaminated fresh fruit and vegetables

    Directory of Open Access Journals (Sweden)

    Radin Dragoslava

    2012-01-01

    Full Text Available Almost any ready-to-eat fruit or vegetable that has been contaminated with pathogens, either from the environment, human or animal feces or through storage, processing and handling, could potentially cause disease. This problem is particularly associated with the occurrence of human intestinal viruses, especially noroviruses, which are of major epidemiological significance as a common cause of both epidemic and sporadic non-bacterial gastroenteritis in humans. Many outbreaks of viral gastroenteritis associated with fresh fruit and vegetables have been described. The rise in incidence of human norovirus outbreaks may be the result of increased consumption of fresh produce, availability of new commodities, export/import and transport around the globe, changes in production practices, improved reporting and detection methods. [PR Projekat Ministarstva nauke Republike Srbije, br. III 46009

  7. A study of design approach of spreading schemes for viral marketing based on human dynamics

    Science.gov (United States)

    Yang, Jianmei; Zhuang, Dong; Xie, Weicong; Chen, Guangrong

    2013-12-01

    Before launching a real viral marketing campaign, it is needed to design a spreading scheme by simulations. Based on a categorization of spreading patterns in real world and models, we point out that the existing research (especially Yang et al. (2010) Ref. [16]) implicitly assume that if a user decides to post a received message (is activated), he/she will take the reposting action promptly (Prompt Action After Activation, or PAAA). After a careful analysis on a real dataset however, it is found that the observed time differences between action and activation exhibit a heavy-tailed distribution. A simulation model for heavy-tailed pattern is then proposed and performed. Similarities and differences of spreading processes between the heavy-tailed and PAAA patterns are analyzed. Consequently, a more practical design approach of spreading scheme for viral marketing on QQ platform is proposed. The design approach can be extended and applied to the contexts of non-heavy-tailed pattern, and viral marketing on other instant messaging platforms.

  8. Viral DNA load of high-risk human papilloma virus is closely associated with the grade of cervical lesions

    OpenAIRE

    Shen, Guqun; Cheng, Jingxin; Wang, Yan; Zhou, Ping; Zhang, Guoqing

    2014-01-01

    This study is to explore the correlation between the viral load of high-risk human papilloma virus (HPV) and the degree of cervical lesions, as well as the follow-up monitoring role of high-risk HPV measurements in the treatment of patients with cervical lesions. Hybrid capture-2 method was used to measure the amount of high-risk HPV load of 361 patients who were enrolled from January 2009 to December 2010 at the Affiliated Tumor Hospital of Xinjiang Medical University, including 76 cases of ...

  9. The burden of norovirus gastroenteritis: an important foodborne and healthcare-related infection.

    Science.gov (United States)

    Belliot, G; Lopman, B A; Ambert-Balay, K; Pothier, P

    2014-08-01

    Human norovirus (NoV) is now recognized as one of the most important causative agents of gastroenteritis in all age groups worldwide. During the course of NoV infection, symptoms are usually mild and disappear within 48 h after onset. The incidence of NoV infection is high, with hundreds of cases per 10 000 of the population, although the number of infections is still underestimated. Epidemiological surveys conducted in Europe and North America have shown that NoV infections constitute a major disease burden, especially for young children and the elderly, in whom NoV infection leads to high rates of hospitalization and mortality. NoV infections are also of concern in hospitals, where viral infections can be persistent in immunocompromised patients. Although the cost of NoV infection in the hospital community has not yet been clearly established, it appears that NoV infections could cost hundreds of thousands of euros in terms of unit closure, and NoV-related sickness in patients and health workers. Besides their clinical burden, NoVs, as foodborne pathogens, also cause to millions of dollars of losses for the healthcare system and the food industry. Recent estimates in the USA showed that, annually, NoV illness cost $2 billion and led to a loss of approximately 5000 quality-adjusted life-years, making NoV one of the top five pathogens causing enteric illnesses. The highest cost among 14 foodborne pathogens is also attributed to human NoV in The Netherlands. This accumulation of evidence underlines the enormous impact of NoV on populations. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  10. Dengue virus genomic variation associated with mosquito adaptation defines the pattern of viral non-coding RNAs and fitness in human cells.

    Directory of Open Access Journals (Sweden)

    Claudia V Filomatori

    2017-03-01

    Full Text Available The Flavivirus genus includes a large number of medically relevant pathogens that cycle between humans and arthropods. This host alternation imposes a selective pressure on the viral population. Here, we found that dengue virus, the most important viral human pathogen transmitted by insects, evolved a mechanism to differentially regulate the production of viral non-coding RNAs in mosquitos and humans, with a significant impact on viral fitness in each host. Flavivirus infections accumulate non-coding RNAs derived from the viral 3'UTRs (known as sfRNAs, relevant in viral pathogenesis and immune evasion. We found that dengue virus host adaptation leads to the accumulation of different species of sfRNAs in vertebrate and invertebrate cells. This process does not depend on differences in the host machinery; but it was found to be dependent on the selection of specific mutations in the viral 3'UTR. Dissecting the viral population and studying phenotypes of cloned variants, the molecular determinants for the switch in the sfRNA pattern during host change were mapped to a single RNA structure. Point mutations selected in mosquito cells were sufficient to change the pattern of sfRNAs, induce higher type I interferon responses and reduce viral fitness in human cells, explaining the rapid clearance of certain viral variants after host change. In addition, using epidemic and pre-epidemic Zika viruses, similar patterns of sfRNAs were observed in mosquito and human infected cells, but they were different from those observed during dengue virus infections, indicating that distinct selective pressures act on the 3'UTR of these closely related viruses. In summary, we present a novel mechanism by which dengue virus evolved an RNA structure that is under strong selective pressure in the two hosts, as regulator of non-coding RNA accumulation and viral fitness. This work provides new ideas about the impact of host adaptation on the variability and evolution of

  11. Discovering hidden viral piracy.

    Science.gov (United States)

    Kim, Eddo; Kliger, Yossef

    2005-12-01

    Viruses and developers of anti-inflammatory therapies share a common interest in proteins that manipulate the immune response. Large double-stranded DNA viruses acquire host proteins to evade host defense mechanisms. Hence, viral pirated proteins may have a therapeutic potential. Although dozens of viral piracy events have already been identified, we hypothesized that sequence divergence impedes the discovery of many others. We developed a method to assess the number of viral/human homologs and discovered that at least 917 highly diverged homologs are hidden in low-similarity alignment hits that are usually ignored. However, these low-similarity homologs are masked by many false alignment hits. We therefore applied a filtering method to increase the proportion of viral/human homologous proteins. The homologous proteins we found may facilitate functional annotation of viral and human proteins. Furthermore, some of these proteins play a key role in immune modulation and are therefore therapeutic protein candidates.

  12. Viral Hepatitis: A through E and Beyond

    Science.gov (United States)

    Viral Hepatitis: A through E and Beyond NATIONAL INSTITUTES OF HEALTH U.S. Department of Health and Human Services National Digestive Diseases Information Clearinghouse What is viral hepatitis? Viral hepatitis is inflammation of the liver caused ...

  13. Viral encephalitis

    Directory of Open Access Journals (Sweden)

    Marcus Tulius T Silva

    2013-09-01

    Full Text Available While systemic viral infections are exceptionally common, symptomatic viral infections of the brain parenchyma itself are very rare, but a serious neurologic condition. It is estimated that viral encephalitis occurs at a rate of 1.4 cases per 100.000 inhabitants. Geography is a major determinant of encephalitis caused by vector-borne pathogens. A diagnosis of viral encephalitis could be a challenge to the clinician, since almost 70% of viral encephalitis cases are left without an etiologic agent identified. In this review, the most common viral encephalitis will be discussed, with focus on ecology, diagnosis, and clinical management.

  14. Human papillomavirus viral load in predicting high-grade CIN in women with cervical smears showing only atypical squamous cells or low-grade squamous intraepithelial lesion

    OpenAIRE

    Santos,André Luis Ferreira; Derchain,Sophie Françoise Mauricette; Martins,Marcos Roberto; Sarian,Luís Otávio Zanatta; Martinez,Edson Zangiacome; Syrjänen,Kari Juhani

    2003-01-01

    CONTEXT: Human papillomavirus (HPV) viral load may have an important role in predicting high-grade cervical intraepithelial neoplasia (CIN) in women with cervical smears showing atypical squamous cells or LSIL. OBJECTIVE: To determine whether the assessment of the viral load of high-risk HPV DNA is useful in predicting the detection of high-grade cervical intraepithelial neoplasia (CIN2 and 3) in women referred because of cervical smears showing only atypical squamous cells or LSIL. TYPE OF S...

  15. The Novel Anticytomegalovirus Compound AIC246 (Letermovir) Inhibits Human Cytomegalovirus Replication through a Specific Antiviral Mechanism That Involves the Viral Terminase ▿

    OpenAIRE

    Goldner, Thomas; Hewlett, Guy; Ettischer, Nicole; Ruebsamen-Schaeff, Helga; Zimmermann, Holger; Lischka, Peter

    2011-01-01

    Human cytomegalovirus (HCMV) remains the leading viral cause of birth defects and life-threatening disease in transplant recipients. All approved antiviral drugs target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Attempts to discover improved anti-HCMV drugs led to the identification of the small-molecular-weight compound AIC246 (Letermovir). AIC246 exhibits outstanding anti-HCMV activity in vitro and in vivo and currently is u...

  16. Proteomic screening of human targets of viral microRNAs reveals functions associated with immune evasion and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Amelia M Gallaher

    Full Text Available Kaposi's sarcoma (KS is caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV. The virus expresses unique microRNAs (miRNAs, but the targets and functions of these miRNAs are not completely understood. In order to identify human targets of viral miRNAs, we measured protein expression changes caused by multiple KSHV miRNAs using pulsed stable labeling with amino acids in cell culture (pSILAC in primary endothelial cells. This led to the identification of multiple human genes that are repressed at the protein level, but not at the miRNA level. Further analysis also identified that KSHV miRNAs can modulate activity or expression of upstream regulatory factors, resulting in suppressed activation of a protein involved in leukocyte recruitment (ICAM1 following lysophosphatidic acid treatment, as well as up-regulation of a pro-angiogenic protein (HIF1α, and up-regulation of a protein involved in stimulating angiogenesis (HMOX1. This study aids in our understanding of miRNA mechanisms of repression and miRNA contributions to viral pathogenesis.

  17. Molecular epidemiology and clinical characterization of group A rotavirus infections in Tunisian children with acute gastroenteritis.

    Science.gov (United States)

    Sdiri-Loulizi, Khira; Ambert-Balay, Katia; Gharbi-Khelifi, Hakima; Hassine, Mouna; Chouchane, Slaheddine; Sakly, Nabil; Neji-Guédiche, Mohamed; Pothier, Pierre; Aouni, Mahjoub

    2011-10-01

    Rotaviruses are the most common cause of severe viral gastroenteritis in early childhood worldwide. Thus, the objectives of our study were to determine the molecular epidemiology and the clinical features of rotavirus gastroenteritis in Tunisia. Between January 2003 and April 2007, a prospective study was conducted on 788 stool samples collected from children under 12 years of age who were suffering from acute gastroenteritis. Rotavirus was detected by multiplex RT-PCR in 27% (n = 213) of samples, among them 79.3% (n = 169) cases were monoinfections. The frequency of rotavirus infections was significantly higher among inpatients (29%) than among outpatients (13%) (P rotavirus diarrhea showed a winter peak, with an unusual peak from June to September. The mean duration of hospitalization was 6.5 ± 8.1 days and the mean age was 15.8 ± 22.8 months for rotavirus monoinfections. Fever, vomiting, abdominal pain, and dehydration were observed in 88, 98, 13, and 80 cases, respectively, in children with rotavirus monoinfections. G3P[8] (45.6%) and G1P[8] (23.9%) were the most common genotypes found in our study. The determination of rotavirus infection prevalence and the characterization of the rotavirus strains circulating will help us to better understand the molecular biology and epidemiology of the disease in our country.

  18. Application of human and animal viral microbial source tracking tools in fresh and marine waters from five different geographical areas.

    Science.gov (United States)

    Rusiñol, Marta; Fernandez-Cassi, Xavier; Hundesa, Ayalkibet; Vieira, Carmen; Kern, Anita; Eriksson, Irene; Ziros, Panos; Kay, David; Miagostovich, Marize; Vargha, Marta; Allard, Annika; Vantarakis, Apostolos; Wyn-Jones, Peter; Bofill-Mas, Sílvia; Girones, Rosina

    2014-08-01

    Integrated river basin management planning to mitigate the impacts of economic, demographic and climate change is an important issue for the future protection of water resources. Identifying sources of microbial contamination via the emerging science of Microbial Source Tracking (MST) plays a key role in risk assessment and the design of remediation strategies. Following an 18-month surveillance program within the EU-FP7-funded VIROCLIME project, specific MST tools were used to assess human markers such as adenoviruses (HAdV) and JC polyomaviruses (JCPyV) and porcine and bovine markers such as porcine adenoviruses (PAdV) and bovine polyomaviruses (BPyV) via quantification with real-time PCR to analyze surface water collected from five sites within different climatic zones: the Negro River (Brazil), Glafkos River (Greece), Tisza River (Hungary), Llobregat River (Spain) and Umeälven River (Sweden). The utility of the viral MST tools and the prevalence and abundance of specific human and animal viruses in the five river catchments and adjacent seawater, which is impacted by riverine contributions from the upstream catchments, were examined. In areas where no sanitation systems have been implemented, sewage can directly enter surface waters, and river water exhibited high viral loads; HAdV and JCPyV could be detected at mean concentrations of 10(5) and 10(4) Genome Copies/Liter (GC/L), respectively. In general, river water samples upstream of urban discharges presented lower human viral loads than downstream sampling sites, and those differences appeared to increase with urban populations but decrease in response to high river flow, as the elevated river water volume dilutes microbial loads. During dry seasons, river water flow decreases dramatically, and secondary effluents can represent the bulk of the riverine discharge. We also observed that ice cover that formed over the river during the winter in the studied areas in North Europe could preserve viral stability

  19. Recombination in human coxsackievirus B5 strains that caused an outbreak of viral encephalitis in Henan, China.

    Science.gov (United States)

    Ma, Hongxia; Huang, Xueyong; Kang, Kai; Li, Xingle; Tang, Xiaoyan; Ren, Yunhui; Wang, Youchun; Zhao, Guirang; Xu, Bianli

    2013-10-01

    In 2011, human coxsackievirus B5 (CVB5) caused an outbreak of viral encephalitis in Henan, China. Complete genome sequence analysis based on two isolates showed that the 5' half of the genome (nt 1-4540) had high similarity (>97 %) to that of CVB5 strain GU376747, and the 3' half (nt 4700-7402) showed high similarity (>96 %) to that of human coxsackievirus B3 (CVB3) strain GQ141875. These isolates had the highest similarity (97.7 %) to the Changchun strain, based on the complete genome, rather than to other CVB5 strains isolated from Henan in recent years. There were therefore at least two groups of CVB5 circulating in Henan Province, which evolved at different rates.

  20. Viral infection of human progenitor and liver-derived cells encapsulated in three-dimensional PEG-based hydrogel

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nam-Joon; Elazar, Menashe; Xiong, Anming; Glenn, Jeffrey S [Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, CCSR Building Room 3115A, 269 Campus Drive, Stanford, CA 94305 (United States); Lee, Wonjae [Mechanical Engineering, Stanford University, Stanford, CA 94305 (United States); Chiao, Eric; Baker, Julie [Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305 (United States); Frank, Curtis W, E-mail: jeffrey.glenn@stanford.ed, E-mail: curt.frank@stanford.ed [Department of Chemical Engineering, Stanford University, Stanford, CA 94305 (United States)

    2009-02-15

    We have studied the encapsulation of human progenitor cells into 3D PEG hydrogels. Replication-incompetent lentivirus promoter reporter vectors were found to efficiently detect the in vivo expression of human hepatic genes in hydrogel-encapsulated liver progenitor cells. Similarly, hydrogel-encapsulated cells could be efficiently infected with hepatitis C virus, and progeny infectious virus could be recovered from the media supernatants of the hydrogels. Provocatively, the diameters of these virus particles range from {approx}50 to 100 nm, while the calculated mesh size of the 8 k hydrogel is 44.6 +- 1.7 A. To reconcile how viral particles can penetrate the hydrogels to infect the encapsulated cells, we propose that microfractures/defects of the hydrogel result in a functional pore size of up to 20 fold greater than predicted by theoretical mesh calculations. These results suggest a new model of hydrogel structure, and have exciting implications for tissue engineering and hepatitis virus studies. (communication)

  1. Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival.

    Science.gov (United States)

    Mangraviti, Antonella; Tzeng, Stephany Y; Gullotti, David; Kozielski, Kristen L; Kim, Jennifer E; Seng, Michael; Abbadi, Sara; Schiapparelli, Paula; Sarabia-Estrada, Rachel; Vescovi, Angelo; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Green, Jordan J; Quinones-Hinojosa, Alfredo

    2016-09-01

    There is a need for enabling non-viral nanobiotechnology to allow safe and effective gene therapy and cell therapy, which can be utilized to treat devastating diseases such as brain cancer. Human adipose-derived mesenchymal stem cells (hAMSCs) display high anti-glioma tropism and represent a promising delivery vehicle for targeted brain tumor therapy. In this study, we demonstrate that non-viral, biodegradable polymeric nanoparticles (NPs) can be used to engineer hAMSCs with higher efficacy (75% of cells) than leading commercially available reagents and high cell viability. To accomplish this, we engineered a poly(beta-amino ester) (PBAE) polymer structure to transfect hAMSCs with significantly higher efficacy than Lipofectamine™ 2000. We then assessed the ability of NP-engineered hAMSCs to deliver bone morphogenetic protein 4 (BMP4), which has been shown to have a novel therapeutic effect by targeting human brain tumor initiating cells (BTIC), a source of cancer recurrence, in a human primary malignant glioma model. We demonstrated that hAMSCs genetically engineered with polymeric nanoparticles containing BMP4 plasmid DNA (BMP4/NP-hAMSCs) secrete BMP4 growth factor while maintaining their multipotency and preserving their migration and invasion capacities. We also showed that this approach can overcome a central challenge for brain therapeutics, overcoming the blood brain barrier, by demonstrating that NP-engineered hAMSCs can migrate to the brain and penetrate the brain tumor after both intranasal and systemic intravenous administration. Critically, athymic rats bearing human primary BTIC-derived tumors and treated intranasally with BMP4/NP-hAMSCs showed significantly improved survival compared to those treated with control GFP/NP-hAMCSs. This study demonstrates that synthetic polymeric nanoparticles are a safe and effective approach for stem cell-based cancer-targeting therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Viral marketing

    OpenAIRE

    Bláhová, Adéla

    2012-01-01

    The aim of my thesis is to provide a comprehensive overview of the viral marketing and to analyze selected viral campaigns. There is a description of advantages and disadvantages of this marketing tool. In the end I suggest for which companies viral marketing is an appropriate form of the promotion.

  3. Viral phylodynamics.

    Directory of Open Access Journals (Sweden)

    Erik M Volz

    Full Text Available Viral phylodynamics is defined as the study of how epidemiological, immunological, and evolutionary processes act and potentially interact to shape viralphylogenies. Since the coining of the term in 2004, research on viral phylodynamics has focused on transmission dynamics in an effort to shed light on how these dynamics impact viral genetic variation. Transmission dynamics can be considered at the level of cells within an infected host, individual hosts within a population, or entire populations of hosts. Many viruses, especially RNA viruses, rapidly accumulate genetic variation because of short generation times and high mutation rates. Patterns of viral genetic variation are therefore heavily influenced by how quickly transmission occurs and by which entities transmit to one another. Patterns of viral genetic variation will also be affected by selection acting on viral phenotypes. Although viruses can differ with respect to many phenotypes, phylodynamic studies have to date tended to focus on a limited number of viral phenotypes. These include virulence phenotypes, phenotypes associated with viral transmissibility, cell or tissue tropism phenotypes, and antigenic phenotypes that can facilitate escape from host immunity. Due to the impact that transmission dynamics and selection can have on viral genetic variation, viral phylogenies can therefore be used to investigate important epidemiological, immunological, and evolutionary processes, such as epidemic spread[2], spatio-temporal dynamics including metapopulation dynamics[3], zoonotic transmission, tissue tropism[4], and antigenic drift[5]. The quantitative investigation of these processes through the consideration of viral phylogenies is the central aim of viral phylodynamics.

  4. Acute Liver Dysfunction in the Course of Norovirus Gastroenteritis

    Directory of Open Access Journals (Sweden)

    H. Nakajima

    2012-01-01

    Full Text Available A 48-year-old female with abdominal pain and malaise who showed delayed symptom of acute gastroenteritis came to see us. Her illness was diagnosed as norovirus infection, but liver dysfunction accompanied this gastroenteritis. We investigated the pathogenesis of this hepatitis for all causes including drugs, but we could not detect norovirus infection. The liver damage improved shortly in course of the gastroenteritis. She recovered completely within 2 weeks without any damage left. Norovirus-induced liver dysfunction is not known, and there is no report in the literature. We report, for the first time, the case of liver dysfunction with norovirus gastroenteritis.

  5. Clinical research of benign infantile convulsions with mild gastroenteritis

    Directory of Open Access Journals (Sweden)

    Wei-bing LI

    2014-03-01

    Full Text Available Cases of benign infantile convulsions with mild gastroenteritis (BICE treated in our hospital from 2008 to 2012 were analyzed retrospectively. Among the 65 cases of convulsions with acute diarrhea, there were 18 cases of BICE, 15 cases of febrile seizures, 13 cases of epilepsy, 6 cases of viral encephalitis, 6 cases of hyponatremia encephalopathy, 3 cases of hypernatremia encephalopathy, 2 cases of toxic encephalopathy, and 2 cases of hypocalcemia convulsion. The convulsion occurred mostly during the first 2 d of the illness and was in a generalized tonic or tonic-clonic form. Positive rotavirus antigens in the BICE patients were detected in 83.33% (15/18. Phenobarbital was administered after the first convulsion (5-10 mg/kg, and diazepam was given intravenously in case of recurrence (0.10-0.30 mg/kg. BICE occurs frequently in infantile and controlling relapse is the main purpose. The prognosis is good. doi: 10.3969/j.issn.1672-6731.2014.03.019

  6. Persistent human papillomavirus infection in the etiology of cervical carcinoma: The role of immunological, genetic, viral and cellular factors

    Directory of Open Access Journals (Sweden)

    Živadinović Radomir

    2014-01-01

    Full Text Available The aim of this paper was to present the role of human papillomavirus (HPV in cervical carcinogenesis from several aspects. By explaining the HPV virus lifecycle and structure, its effect on cervical cell cycle and subversion of immune response can be better understood. Early E region of the viral genome encodes proteins that are directly involved in carcinogenesis. The E6 protein binds to p53 protein (product of tumor-suppressor gene blocking and degrading it, which in turn prevents cell cycle arrest and apoptosis induction. E6 is also capable of telomerase activation, which leads to cell immortalization; it also reacts with host proto-oncogene c-jun, responsible for transcription, shortens G1 phase and speeds up the transition from G1 to S phase of the cells infected by HPV. E7 forms bonds with retinoblastoma protein (product of tumor-suppressor gene and inactivates it. It can inactivate cyclin inhibitors p21, p27, and abrogate the mitotic spindle checkpoint with the loss of protective effect of pRB and p53. The immune system cannot initiate early immunological reaction since the virus is non-lytic, while the concentration of viral proteins - antigens is low and has a basal intracellular position. Presentation through Langerhans cells (LC is weak, because the number of these cells is low due to the effect of HPV. E7 HPV reduces the expression of E-cadherin, which is responsible for LC adhesion to HPVtransformed keratinocytes. Based on these considerations, it may be concluded that the process of cervical carcinogenesis includes viral, genetic, cellular, molecular-biological, endocrine, exocrine and immunological factors.

  7. PTB Binds to the 3’ Untranslated Region of the Human Astrovirus Type 8: A Possible Role in Viral Replication

    Science.gov (United States)

    Espinosa-Hernández, Wendy; Velez-Uriza, Dora; Valdés, Jesús; Vélez-Del Valle, Cristina; Salas-Benito, Juan; Martínez-Contreras, Rebeca; García-Espítia, Matilde; Salas-Benito, Mariana; Vega-Almeida, Tania; De Nova-Ocampo, Mónica

    2014-01-01

    The 3′ untranslated region (3′UTR) of human astroviruses (HAstV) consists of two hairpin structures (helix I and II) joined by a linker harboring a conserved PTB/hnRNP1 binding site. The identification and characterization of cellular proteins that interact with the 3′UTR of HAstV-8 virus will help to uncover cellular requirements for viral functions. To this end, mobility shift assays and UV cross-linking were performed with uninfected and HAstV-8-infected cell extracts and HAstV-8 3′UTR probes. Two RNA-protein complexes (CI and CII) were recruited into the 3′UTR. Complex CII formation was compromised with cold homologous RNA, and seven proteins of 35, 40, 45, 50, 52, 57/60 and 75 kDa were cross-linked to the 3′UTR. Supermobility shift assays indicated that PTB/hnRNP1 is part of this complex, and 3′UTR-crosslinked PTB/hnRNP1 was immunoprecipitated from HAstV-8 infected cell-membrane extracts. Also, immunofluorescence analyses revealed that PTB/hnRNP1 is distributed in the nucleus and cytoplasm of uninfected cells, but it is mainly localized perinuclearly in the cytoplasm of HAstV-8 infected cells. Furthermore, the minimal 3′UTR sequences recognized by recombinant PTB are those conforming helix I, and an intact PTB/hnRNP1-binding site. Finally, small interfering RNA-mediated PTB/hnRNP1 silencing reduced synthesis viral genome and virus yield in CaCo2 cells, suggesting that PTB/hnRNP1 is required for HAstV replication. In conclusion, PTB/hnRNP1 binds to the 3′UTR HAstV-8 and is required or participates in viral replication. PMID:25406089

  8. Promyelocytic leukemia nuclear bodies provide a scaffold for human polyomavirus JC replication and are disrupted after development of viral inclusions in progressive multifocal leukoencephalopathy.

    Science.gov (United States)

    Shishido-Hara, Yukiko; Higuchi, Kayoko; Ohara, Sinji; Duyckaerts, Charles; Hauw, Jean-Jacques; Uchihara, Toshiki

    2008-04-01

    Progressive multifocal leukoencephalopathy is a fatal demyelinating disorder due to human polyomavirus JC infection in which there are viral inclusions in enlarged nuclei of infected oligodendrocytes. We report that the pathogenesis of this disease is associated with distinct subnuclear structures known as promyelocytic leukemia nuclear bodies (PML-NBs). Postmortem brain tissues from 5 patients with the disease were examined. Affected cells with enlarged nuclei contained distinct dot-like subnuclear PML-NBs that were immunopositive for PML protein and nuclear body protein Sp100. Major and minor viral capsid proteins and proliferating cell nuclear antigen, an essential component for DNA replication, colocalized with PML-NBs. By in situ hybridization, viral genomic DNA showed dot-like nuclear accumulation, and by electron microscopy, virus-like structures clustered in subnuclear domains, indicating that PML-NBs are the site of viral DNA replication and capsid assembly. Molecules involved in the ubiquitin proteosome pathway (i.e. ubiquitin and small ubiquitin-like modifier 1) did not accumulate in the nuclei with viral inclusions, indicating that cell degeneration may not be dependent on this pathway. When viral progeny production was advanced, PML-NBs were disrupted. These data suggest that: 1) PML-NBs allow for efficient viral propagation by providing scaffolds, 2) disruption of PML-NBs is independent of the ubiquitin-proteasome pathway, and 3) this disruption probably heralds oligodendrocyte degeneration and the resulting demyelination.

  9. Myeloid ecotropic viral integration site 1 inhibits cell proliferation, invasion or migration in human gastric cancer.

    Science.gov (United States)

    Song, Fei; Wang, Hong; Wang, Yingying

    2017-10-27

    Myeloid ecotropic viral integration site 1 (MEIS1) has been identified to be a potential tumor suppressor in some cancers. However, the mechanisms underlying MEIS1-induced cancer development and progression were not clear. Here, we investigated the expression and role of MEIS1 in gastric cancer. In vivo , we analyzed tumor growth using nude mice model. In the present study, MEIS1 expression was obviously decreased in GC cell lines compared with that in normal gastric cell lines (all pmigration assay revealed that MEIS1 affects cell invasion and migration, and inhibited epithelial-mesenchymal transition (EMT). Finally, MEIS1 inhibits MKN28 cell growth in nude mice model. In conclusion, our study suggested that MEIS1 plays an important role in regulating cell survival, proliferation, anchorage-independent growth, cell cycle, apoptosis and metastasis. Thus, MEIS1 might be recommended as an effective target for GC patients.

  10. [Comparative analysis on clinical manifestations for gastroenteritis caused by norovirus and rotavirus].

    Science.gov (United States)

    Deng, Li; Jia, Li-ying; Qian, Yuan; Chen, Dong-mei; Zhang, You; Zhang, Yan-ling

    2009-04-01

    To compare the clinical manifestations of gastroenteritis caused by norovirus and rotavirus in infants and young children in Beijing. Stool specimens were collected from infants and young children with acute diarrhea who visited the Affiliated Children's Hospital to Capital Institute of Pediatrics from January 2002 to December 2006. Registration form was designed for clinical data collection for each patient from whom specimen was collected. Poly-acrylamide gel electrophoresis (PAGE) and enzyme immunoassay (EIA) were used to detect rotavirus and Human norovirus, respectively. Among 779 stool specimens tested for rotavirus, 263 were positive (33.8%), and norovirus positive specimens were 79 out of 318 (24.8%) specimens tested. Most of the clinical manifestations of gastroenteritis caused by these two viruses were quite similar with no significant difference, except for fever. The seasonal distribution of these two viruses were different with the peak of rotavirus infection was in cold weather between October and January, as indicated by the peak of the positive rates of the virus detection. The infection of norovirus seemed no obvious peak in the year. Rotavirus is the most important pathogen for acute diarrhea among infants and young children while. Norovirus is also an important pathogen for acute gastroenteritis in infants and young children. No significant difference was found out for clinical manifestations for the gastroenteritis caused by these two viruses.

  11. Human Cytomegalovirus-Encoded Receptor US28 Is Expressed in Renal Allografts and Facilitates Viral Spreading In Vitro.

    Science.gov (United States)

    Lollinga, Wouter T; de Wit, Raymond H; Rahbar, Afsar; Vasse, Gwenda F; Davoudi, Belghis; Diepstra, Arjan; Riezebos-Brilman, Annelies; Harmsen, Martin C; Hillebrands, Jan-Luuk; Söderberg-Naucler, Cecilia; van Son, Willem J; Smit, Martine J; Sanders, Jan-Stephan; van den Born, Jacob

    2017-03-01

    Renal transplantation is the preferred treatment for patients with end-stage renal disease. Human cytomegalovirus (HCMV) activation is associated with decreased renal graft function and survival. Human cytomegalovirus encodes several immune modulatory proteins, including the G protein-coupled receptor US28, which scavenges human chemokines and modulates intracellular signaling. Our aim was to identify the expression and localization of US28 in renal allograft biopsies by immunohistochemistry and determine its role in viral spreading in vitro. Immunohistochemistry revealed US28 in 31 of 34 renal transplant biopsies from HCMV-seropositive donors. Expression was independent of HCMV viremia or IgG serostatus. US28 was predominantly expressed in the cytoplasm of vascular smooth muscle cells (VSMCs) and tubular epithelial cells, with a median positivity of 20% and 40%, respectively. Also, US28-positive cells were present within arterial neointima. In contrast to US28, HCMV-encoded immediate early antigen was detected in less than 5% of VSMCs, tubular epithelial cells, interstitial endothelium, interstitial inflammatory infiltrates, and glomerular cells.Primary VSMCs were infected with green fluorescent protein-tagged wild type or US28-deficient HCMV. The viral spreading of US28-deficient HCMV, via culture medium or cell-to-cell transmission, was significantly impeded as shown by green fluorescent protein (ie, infected) cell quantification and quantitative real-time polymerase chain reaction. Additionally, the number and size of foci was smaller. In summary, HCMV-encoded US28 was detected in renal allografts from HCMV-positive donors independent of viremia and serostatus. Also, US28 facilitates HCMV spreading in VSMCs in vitro. Because the vasculature is affected in chronic renal transplant dysfunction, US28 may provide a potential target for therapeutic intervention.

  12. Prediction of viral microRNA precursors based on human microRNA precursor sequence and structural features.

    Science.gov (United States)

    Kumar, Shiva; Ansari, Faraz A; Scaria, Vinod

    2009-08-20

    MicroRNAs (small approximately 22 nucleotide long non-coding endogenous RNAs) have recently attracted immense attention as critical regulators of gene expression in multi-cellular eukaryotes, especially in humans. Recent studies have proved that viruses also express microRNAs, which are thought to contribute to the intricate mechanisms of host-pathogen interactions. Computational predictions have greatly accelerated the discovery of microRNAs. However, most of these widely used tools are dependent on structural features and sequence conservation which limits their use in discovering novel virus expressed microRNAs and non-conserved eukaryotic microRNAs. In this work an efficient prediction method is developed based on the hypothesis that sequence and structure features which discriminate between host microRNA precursor hairpins and pseudo microRNAs are shared by viral microRNA as they depend on host machinery for the processing of microRNA precursors. The proposed method has been found to be more efficient than recently reported ab-initio methods for predicting viral microRNAs and microRNAs expressed by mammals.

  13. Universal real-time PCR assay for quantitation and size evaluation of residual cell DNA in human viral vaccines.

    Science.gov (United States)

    André, Murielle; Reghin, Sylviane; Boussard, Estelle; Lempereur, Laurent; Maisonneuve, Stéphane

    2016-05-01

    Residual host cellular DNA (rcDNA) is one of the principal risk associated with continuous cell lines derived medicines such as viral vaccines. To assess rcDNA degradation, we suggest two quantitative real-time PCR assays designed to separately quantify target sequences shorter and longer than the 200 bp risk limit, the relative abundance of both targets reflecting the extent of rcDNA fragmentation. The conserved multicopy ribosomal 18S RNA gene was targeted to detect host cell templates from most mammalian cell substrates commonly used in the manufacture of human viral vaccines. The detection range of the method was assessed on purified DNA templates from different animal origins. The standard calibrator origin and structural conformation were shown crucial to achieve accurate quantification. Artificial mixtures of PCR products shorter and longer than 200 bp were used as a model to check the ability of the assay to estimate the fragment size distribution. The method was successfully applied to a panel of Vero cell derived vaccines and could be used as a universal method for determination of both content and size distribution of rcDNA in vaccines. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  14. Understanding MHC class I presentation of viral antigens by human dendritic cells as a basis for rational design of therapeutic vaccines

    Directory of Open Access Journals (Sweden)

    Nadine eVan Montfoort

    2014-04-01

    Full Text Available Effective viral clearance requires the induction of virus-specific CD8+ cytotoxic T lymphocytes (CTL. Since dendritic cells (DC have a central role in initiating and shaping virus-specific CTL responses, it is important to understand how DC initiate virus-specific CTL responses. Some viruses can directly infect DC, which theoretically allows direct presentation of viral antigens to CTL, but many viruses target other cells than DC and thus the host depends on the cross-presentation of viral antigens by DC to activate virus-specific CTL.Research in mouse models has highly enhanced our understanding of the mechanisms underlying cross-presentation and the DC subsets involved, however, these results cannot be readily translated towards the role of human DC in MHC class I antigen presentation of human viruses. Here, we summarize the insights gained in the past 20 years on MHC class I presentation of viral antigen by human DC and add to the current debate on the capacities of different human DC subsets herein. Furthermore, possible sources of viral antigens and essential DC characteristics for effective induction of virus-specific CTL are evaluated.We conclude that cross-presentation is not only an efficient mechanism exploited by DC to initiate immunity to viruses that do not infect DC but also to viruses that do infect DC, because cross-presentation has many conceptual advantages and bypasses direct immune modulatory effects of the virus on its infected target cells. Since knowledge on the mechanism of viral antigen presentation and the preferred DC subsets is crucial for rational vaccine design, the obtained insights are very instrumental for the development of effective anti-viral immunotherapy.

  15. A subset of human immunodeficiency virus type 1 long-term non-progressors is characterized by the unique presence of ancestral sequences in the viral population.

    Science.gov (United States)

    Bello, Gonzalo; Casado, Concepción; Sandonis, Virginia; Alonso-Nieto, Manuela; Vicario, José Luis; García, Soledad; Hernando, Victoria; Rodríguez, Carmen; del Romero, Jorge; López-Galíndez, Cecilio

    2005-02-01

    Within human immunodeficiency virus type 1 (HIV-1)-infected patients, there are those who have been infected for more than 10 years with a CD4+ cell count of >500 cells microl(-1) and who remain asymptomatic without antiretroviral therapy; these patients are designated long-term non-progressors (LTNPs). In a set of 16 LTNPs, viral dating, DNA viral load, quasispecies heterogeneity and antibody (Ab) titres against gp160 and beta2 microglobulin (beta2m) were determined. Plasma viral RNA and CD4+ and CD8+ T-cell numbers were estimated in more than three samples per patient. Host genetic characteristics, such as Delta32-CCR5 genotype and human leukocyte antigen (HLA) genotype and supertypes, and clinical-epidemiological factors were evaluated. Dating of global populations and of DNA and RNA viral quasispecies identified two subsets of patients: one displaying only ancestral sequences and the other displaying predominantly modern sequences. The ancestral patients displayed a significant reduction in RNA and DNA viral loads, quasispecies heterogeneity, CD8+ cell number, anti-gp160 Ab titres and beta2m level, and they were also associated with better use of safe-sex practices and higher presence of the HLA sB58 supertype than the modern subset. Viral dating has therefore permitted the segregation of LTNPs into two subsets that show very different virological, immunological, host and clinical-epidemiological characteristics. Moreover, whereas the modern subset displayed low levels of virus replication, the ancestral group displayed not only a very limited virus replication, often to undetectable levels, but also very slow or arrested viral evolution, maintaining the close relationship of the viral population to the transmitted virus.

  16. Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia.

    Science.gov (United States)

    Timmermans, Ans; Melendrez, Melanie C; Se, Youry; Chuang, Ilin; Samon, Nou; Uthaimongkol, Nichapat; Klungthong, Chonticha; Manasatienkij, Wudtichai; Thaisomboonsuk, Butsaya; Tyner, Stuart D; Rith, Sareth; Horm, Viseth Srey; Jarman, Richard G; Bethell, Delia; Chanarat, Nitima; Pavlin, Julie; Wongstitwilairoong, Tippa; Saingam, Piyaporn; El, But Sam; Fukuda, Mark M; Touch, Sok; Sovann, Ly; Fernandez, Stefan; Buchy, Philippe; Chanthap, Lon; Saunders, David

    2016-01-01

    Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1-77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza was found in 168 cases (29%) and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (Cambodia isolates (94.4% genome conservation) than to 13 Thai isolates (75.9% genome conservation), despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7%) and parainfluenza virus (3.8%), while non-polio enteroviruses (10.3%) were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in light of an increasingly important role of permissive mutations in influenza virus evolution

  17. Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia.

    Directory of Open Access Journals (Sweden)

    Ans Timmermans

    Full Text Available Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1-77 presenting with influenza-like-illness (ILI at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV and EV71. Influenza was found in 168 cases (29% and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (<20%. Western Cambodian H1N1(2009 isolate genomes were more closely related to 10 earlier Cambodia isolates (94.4% genome conservation than to 13 Thai isolates (75.9% genome conservation, despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7% and parainfluenza virus (3.8%, while non-polio enteroviruses (10.3% were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in

  18. Intravenous rehydration for gastroenteritis: how long does it really take?

    Science.gov (United States)

    Bender, Brenda J; Ozuah, Philip O

    2004-04-01

    For treatment of mild to moderate dehydration arising from viral gastroenteritis, the American Academy of Pediatrics recommends oral rehydration therapy over a 4-hour period. However, oral rehydration therapy remains largely underused by emergency physicians. Studies suggest that a major barrier is a perception that the time requirement for oral rehydration therapy is too long relative to intravenous (IV) hydration. : To test the hypothesis that children who receive IV hydration for gastroenteritis spend significantly less than 4 hours in the emergency department (ED). A prospective case series involving a consecutive sample of 549 children treated with IV hydration for mild to moderate dehydration at an urban pediatric ED. Treatment time was defined as period elapsed between when a physician placed a patient in an ED room and when he/she discharged the patient. We excluded time spent in the waiting room before seeing a physician. Using a standardized procedure, we collected data in September/October 2000 (fall), November 2000 to January 2001 (winter), and April/May 2001 (spring). To provide a measure of average pass-through time at this ED, we also collected data on all patients treated during consecutive 7-day periods in the fall (n = 502), winter (n = 776), and spring (n = 653). We performed univariate analysis of continuous variables using t tests for independent samples. 549 subjects received IV treatment for dehydration; of whom 55% were female, and mean age was 9.7 years. Treatment time for patients undergoing IV hydration exceeded 4 hours (mean = 5.4 +/- 2.4 hours; median = 5.0 hours). Mean time for IV treatment of dehydration was significantly longer than the mean time for treating other patients (5.4 vs. 1.2 hours, P < 0.001). Mean IV treatment times were: fall (5.1 hours), winter (5.5 hours), and spring (4.7 hours). Mean treatment time exceeded 4 hours regardless of time of day, day of the week, or age of child. Contrary to our hypothesis, mean treatment

  19. Human hepatitis B viral e antigen and its precursor P20 inhibit T lymphocyte proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Purvina, Maija; Hoste, Astrid; Rossignol, Jean-Michel [Universite de Versailles-Saint-Quentin-en-Yvelines, Laboratoire de Genetique et Biologie Cellulaire, EA 4589, 45 avenue des Etats-Unis, 78035 Versailles (France); Lagaudriere-Gesbert, Cecile, E-mail: cecile.lagaudriere-gesbert@u-psud.fr [Universite de Versailles-Saint-Quentin-en-Yvelines, Laboratoire de Genetique et Biologie Cellulaire, EA 4589, 45 avenue des Etats-Unis, 78035 Versailles (France)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer P20, precursor of the HBeAg, interacts with the cellular protein gC1qR. Black-Right-Pointing-Pointer HBeAg and P20 bind to T cell surface and inhibit mitogen-induced T cell division. Black-Right-Pointing-Pointer HBeAg and P20 inhibition of T cell proliferation is gC1qR and IL-1RAcP-independent. -- Abstract: The hepatitis B virus (HBV) Precore protein is processed through the secretory pathway directly as HBeAg or with the generation of an intermediate (P20). Precore gene has been shown to be implicated in viral persistence, but the functions of HBeAg and its precursors have not been fully elucidated. We show that the secreted proteins HBeAg and P20 interact with T cell surface and alter Kit-225 and primary T cells proliferation, a process which may facilitate the establishment of HBV persistence. Our data indicate that the N-terminal end of Precore is important for these inhibitory effects and exclude that they are dependent on the association of HBeAg and P20 with two characterized cell surface ligands, the Interleukin-1 Receptor Accessory Protein and gC1qR (present study).

  20. Dry-heat treatment process for enhancing viral safety of an antihemophilic factor VIII concentrate prepared from human plasma.

    Science.gov (United States)

    Kim, In Seop; Choi, Yong Woon; Kang, Yong; Sung, Hark Mo; Shin, Jeong Sup

    2008-05-01

    Viral safety is a prerequisite for manufacturing clinical antihemophilic factor VIII concentrates from human plasma. With particular regard to the hepatitis A virus (HAV), a terminal dry-heat treatment (100 degrees for 30 min) process, following lyophilization, was developed to improve the virus safety of a solvent/detergent-treated antihemophilic factor VIII concentrate. The loss of factor VIII activity during dry-heat treatment was of about 5%. No substantial changes were observed in the physical and biochemical characteristics of the dry-heat-treated factor VIII compared with those of the factor VIII before dry-heat treatment. The dry-heat-treated factor VIII was stable for up to 24 months at 4oC. The dry-heat treatment after lyophilization was an effective process for inactivating viruses. The HAV, murine encephalomyocarditis virus (EMCV), and human immunodeficiency virus (HIV) were completely inactivated to below detectable levels within 10 min of the dry-heat treatment. Bovine herpes virus (BHV) and bovine viral diarrhea virus (BVDV) were potentially sensitive to the treatment. However porcine parvovirus (PPV) was slightly resistant to the treatment. The log reduction factors achieved during lyophilization and dry-heat treatment were > or =5.55 for HAV, > or =5.87 for EMCV, > or =5.15 for HIV, 6.13 for BHV, 4.46 for BVDV, and 1.90 for PPV. These results indicate that dry-heat treatment improves the virus safety of factor VIII concentrates, without destroying the activity. Moreover, the treatment represents an effective measure for the inactivation of non-lipid-enveloped viruses, in particular HAV, which is resistant to solvent/detergent treatment.

  1. Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

    Directory of Open Access Journals (Sweden)

    Laura Hewitson

    2014-01-01

    Full Text Available In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV. Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA, was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae, Bacteroidaceae, and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.

  2. Detection of viral proteins in human cells lines by xeno-proteomics: elimination of the last valid excuse for not testing every cellular proteome dataset for viral proteins.

    Science.gov (United States)

    Chernobrovkin, Alexey L; Zubarev, Roman A

    2014-01-01

    Cell cultures used routinely in proteomic experiments may contain proteins from other species because of infection, transfection or just contamination. Since infection or contamination may affect the results of a biological experiment, it is important to test the samples for the presence of "alien" proteins. Usually cells are tested only for the most common infections, and most of the existing tests are targeting specific contaminations. Here we describe a three-step procedure for reliable untargeted detection of viral proteins using proteomics data, and recommend this or similar procedure to be applied to every proteomics dataset submitted for publication.

  3. Detection of viral proteins in human cells lines by xeno-proteomics: elimination of the last valid excuse for not testing every cellular proteome dataset for viral proteins.

    Directory of Open Access Journals (Sweden)

    Alexey L Chernobrovkin

    Full Text Available Cell cultures used routinely in proteomic experiments may contain proteins from other species because of infection, transfection or just contamination. Since infection or contamination may affect the results of a biological experiment, it is important to test the samples for the presence of "alien" proteins. Usually cells are tested only for the most common infections, and most of the existing tests are targeting specific contaminations. Here we describe a three-step procedure for reliable untargeted detection of viral proteins using proteomics data, and recommend this or similar procedure to be applied to every proteomics dataset submitted for publication.

  4. DIAGNOSTICS AND THERAPY IN CHILDREN'S ACUTE GASTROENTERITIS

    Directory of Open Access Journals (Sweden)

    M.D. Bakradze

    2007-01-01

    Full Text Available The work aimed at studying a series of diagnostic aspects and determination of the possible treatment of children with acute gastroenetrites according to the protocol based on international recommendations and standards. The study involved 130 children, of whom in 71 patients the presence of rotavirus antigen in coprofilters was checked via latex particle agglutination method. In 85% rotavirus infection was confirmed. It was shown that the majority of cases fall on November to may. Infant and early children are the most susceptible to rotavirus gastroenteritis. The analysis of therapy results showed that antibioticsfree treatment of watery diarrhea patients worked well, and prescription of antibacterial therapy for the concomitant bacterial infection does not influence the time of gastroenteritis reduction. The results of dehydration therapy show that oral rehydration is not always effective for the 2nd stage dehydration, especially with late treatment. However, the time of recovery (diarrhea reduction does not depend on the type of rehydration or symptomatic therapy. A diagnostic algorithm that helps use the minimum diagnostic methods in stationary conditions and at the same time provides the optimum scope of therapeutic intervention was worked out.Key words: rotavirus infection, children, rehydration, antibacterial therapy.

  5. Aichi virus infection in children with acute gastroenteritis in Finland.

    Science.gov (United States)

    Kaikkonen, S; Räsänen, S; Rämet, M; Vesikari, T

    2010-08-01

    Aichi virus has been proposed as a novel causative agent of acute gastroenteritis. In addition to several Asian countries, South America and Africa, Aichi virus has also recently been found in Europe. Our objective was to study the causative role of Aichi virus in children with acute gastroenteritis in Finland. We analysed 595 stool specimens from infants in an efficacy trial of rotavirus vaccine and 468 stool specimens from children in a hospital-based epidemiological and aetiological study of acute gastroenteritis. The screening was done by nested reverse transcription-polymerase chain reaction amplifying a 519-bp segment and a 223-bp segment in the 3CD junction region of non-structural proteins. Aichi virus was detected in five stool samples (0.5%), of which four were co-infections with other gastroenteritis viruses. Two Aichi virus genotypes, A and B, were found. Aichi virus appears to be rare in children with acute gastroenteritis in Finland.

  6. Utilization of replication-competent XMRV reporter-viruses reveals severe viral restriction in primary human cells.

    Directory of Open Access Journals (Sweden)

    Christina Martina Stürzel

    Full Text Available The gammaretrovirus termed xenotropic murine leukemia virus-related virus (XMRV was described to be isolated from prostate cancer tissue biopsies and from blood of patients suffering from chronic fatigue syndrome. However, many studies failed to detect XMRV and to verify these disease associations. Data suggesting the contamination of specimens in particular by PCR-based methods and recent reports demonstrating XMRV generation via recombination of two murine leukemia virus precursors raised serious doubts about XMRV being a genuine human pathogen. To elucidate cell tropism of XMRV, we generated replication competent XMRV reporter viruses encoding a green fluorescent protein or a secretable luciferase as tools to analyze virus infection of human cell lines or primary human cells. Transfection of proviral DNAs into LNCaP prostate cancer cells resulted in readily detectably reporter gene expression and production of progeny virus. Inoculation of known XMRV susceptible target cells revealed that these virions were infectious and expressed the reporter gene, allowing for a fast and highly sensitive quantification of XMRV infection. Both reporter viruses were capable of establishing a spreading infection in LNCaP and Raji B cells and could be easily passaged. However, after inoculation of primary human blood cells such as CD4 T cells, macrophages or dendritic cells, infection rates were very low, and a spreading infection was never established. In line with these results we found that supernatants derived from these XMRV infected primary cell types did not contain infectious virus. Thus, although XMRV efficiently replicated in some human cell lines, all tested primary cells were largely refractory to XMRV infection and did not support viral spread. Our results provide further evidence that XMRV is not a human pathogen.

  7. Rate of hepatitis C viral clearance by human livers in human patients: Liver transplantation modeling primary infection and implications for studying entry inhibition.

    Directory of Open Access Journals (Sweden)

    Michael G Hughes

    Full Text Available To better understand the dynamics of early hepatitis C virus (HCV infection, we determined how rapidly non-cirrhotic HCV-uninfected liver allografts clear HCV from the circulation of cirrhotic HCV-infected patients at the time of transplantation but before administration of immunosuppression. Specifically, we characterized serum HCV kinetics during the first 90 min of reperfusion for 19 chronically HCV-infected patients transplanted with an HCV-uninfected liver by measuring serum viral load immediately prior to reperfusion (t = 0 and then every 15 min for a total of 90 min (t = 90. Immunosuppression was withheld until all samples were taken to better model primary infection. During this period, rates of viral clearance varied more than 20-fold with a median rate constant of 0.0357 1/min, range 0.0089-0.2169; half-life (minutes median 19.4, range 3.2-77.8. The majority of viral clearance occurred within the first 60 min. The amount of blood transfused during this 90-min period (a potential confounding variable of this human liver transplant model of primary infection accounted for 53% and 59% of k (r = 0.53, p = 0.05 and half-life (r = 0.59, p = 0.03 variability, respectively. No other clinical variables tested (age, allograft weight, and degree of reperfusion injury as assessed by peak postoperative ALT or AST accounted for the remaining variability (p>0.05.In a human liver transplant model of primary infection, HCV rapidly clears the bloodstream. With approximately 90% of clearance occurring in the first 90 minutes of reperfusion, studies of HCV entry inhibition could utilize rate of clearance during this early period as an outcome measure.

  8. Water extract of Pueraria lobata Ohwi has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines

    Directory of Open Access Journals (Sweden)

    Tzeng-Jih Lin

    2013-12-01

    Full Text Available Human respiratory syncytial virus (HRSV infects all age groups and causes bronchiolitis, pneumonia, and acute respiratory distress syndrome with a significant mortality rate. To date, only ribavirin has been used to manage HRSV infection. However, ribavirin is expensive with an only modest effect. Furthermore, ribavirin has several side effects, which means it has limited clinical benefit. Pueraria lobata Ohwi (P. lobata is a common ingredient of Ge-Gen-Tang (Kakkon-to and Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to, which are prescriptions of Chinese traditional medicine proven to have antiviral activity against HRSV. Therefore, it was hypothesized that P. lobata might be effective against HRSV. To find a cost-effective therapeutic modality, both human upper (HEp-2 and lower (A549 respiratory tract cell lines were used to test the hypothesis that P. lobata could inhibit HRSV-induced plaque formation. Results showed that the water extract of P. lobata was effective (p < 0.0001 against HRSV-induced plaque formation. P. lobata was more effective when given prior to viral inoculation (p < 0.0001 by inhibiting viral attachment (p < 0.0001 and penetration (p < 0.0001. However, supplementation with P. lobata could not stimulate interferon secretion after HRSV infection. In conclusion, P. lobata has antiviral activity against HRSV-induced plaque formation in airway mucosa mainly by inhibiting viral attachment and internalization. Further identification of effective constituents could contribute to the prevention of HRSV infection.

  9. Using Bovine Viral Diarrhea Virus (BVDV) As Surrogate for Human Hepatitis C Virus

    Science.gov (United States)

    This test is designed to validate virucidal effectiveness claims for a product to be registered as a virucide. It determines the potential of the test agent to disinfect hard surfaces contaminated with human Hepatitis C virus (HCV).

  10. Viral metagenomics on animals as a tool for the detection of zoonoses prior to human infection?

    National Research Council Canada - National Science Library

    Temmam, Sarah; Davoust, Bernard; Berenger, Jean-Michel; Raoult, Didier; Desnues, Christelle

    2014-01-01

    .... Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod...

  11. Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Clément Guillot

    Full Text Available Hepatitis B virus (HBV infection remains a major public health concern worldwide with 240 million individuals chronically infected and at risk of developing cirrhosis and hepatocellular carcinoma. Current treatments rarely cure chronic hepatitis B infection, highlighting the need for new anti-HBV drugs. Nucleic acid polymers (NAPs are phosphorothioated oligonucleotides that have demonstrated a great potential to inhibit infection with several viruses. In chronically infected human patients, NAPs administration lead to a decline of blood HBsAg and HBV DNA and to HBsAg seroconversion, the expected signs of functional cure. NAPs have also been shown to prevent infection of duck hepatocytes with the Avihepadnavirus duck hepatitis B virus (DHBV and to exert an antiviral activity against established DHBV infection in vitro and in vivo. In this study, we investigated the specific anti-HBV antiviral activity of NAPs in the HepaRG human hepatoma cell line and primary cultures of human hepatocytes. NAPs with different chemical features (phosphorothioation, 2'O-methyl ribose, 5-methylcytidine were assessed for antiviral activity when provided at the time of HBV inoculation or post-inoculation. NAPs dose-dependently inhibited HBV entry in a phosphorothioation-dependent, sequence-independent and size-dependent manner. This inhibition of HBV entry by NAPs was impaired by 2'O-methyl ribose modification. NAP treatment after viral inoculation did not elicit any antiviral activity.

  12. Viral Kinetics of Primary Dengue Virus Infection in Non-Human Primates: A Systematic Review and Individual Pooled Analysis

    Science.gov (United States)

    Althouse, Benjamin M.; Durbin, Anna P.; Hanley, Kathryn A.; Halstead, Scott B.; Weaver, Scott C.; Cummings, Derek A. T.

    2014-01-01

    Viremia kinetics directly influence the clinical course and transmission dynamics of DENV, but many aspects of viral dynamics remain unknown. Non-human primates (NHP) have been used as a model system for DENV infection for decades. Here, we identify papers with experimentally-infected NHP and estimate the time to- and duration of viremia as well as estimate associations between these and serotype, inoculating dose, viremia assay, and species of NHP. We estimate the time to viremia in rhesus macaques to range from 2.63 to 3.32 days for DENV-2 and -1 and the duration to range from 3.13 to 5.13 days for DENV-4 and -2. We find no differences between non-human primates for time to viremia or duration, and a significant negative relationship between inoculating dose and duration of viremia. These results aide in understanding the transmission dynamics of sylvatic DENV non-human primates, an issue of growing importance as dengue vaccines become available. PMID:24606701

  13. Viral gastrointestinal syndrome in our environment

    Directory of Open Access Journals (Sweden)

    Patić A.

    2014-01-01

    Full Text Available Viral gastrointestinal syndrome is a cause of morbidity and death worldwide. Infection is spread through contact with an infected person, as well as through contaminated food and water. A lethal outcome is possible in infants and young children due to dehydration and electrolyte imbalance. The study included 141 patients with gastroenteritis from Vojvodina. Real-Time PCR method in stool samples was used to determine the presence of rota-, noro-, and astrovirus nucleic acid. Out of 141 patients with gastroenteritis, 60.3% were confirmed to have one of the three viruses. Rotavirus was significantly more common in children up to 3 years of age (43.3%. Norovirus was more frequently detected in patients older than 20 (50%. These infections started in collectives. Astrovirus was detected in four patients (2.8%. The results confirm the necessity to implement PCR in routine diagnostics for the proper treatment of patients.

  14. The Novel Anticytomegalovirus Compound AIC246 (Letermovir) Inhibits Human Cytomegalovirus Replication through a Specific Antiviral Mechanism That Involves the Viral Terminase ▿

    Science.gov (United States)

    Goldner, Thomas; Hewlett, Guy; Ettischer, Nicole; Ruebsamen-Schaeff, Helga; Zimmermann, Holger; Lischka, Peter

    2011-01-01

    Human cytomegalovirus (HCMV) remains the leading viral cause of birth defects and life-threatening disease in transplant recipients. All approved antiviral drugs target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Attempts to discover improved anti-HCMV drugs led to the identification of the small-molecular-weight compound AIC246 (Letermovir). AIC246 exhibits outstanding anti-HCMV activity in vitro and in vivo and currently is undergoing a clinical phase IIb trial. The initial mode-of-action studies suggested that the drug acts late in the HCMV replication cycle via a mechanism distinct from that of polymerase inhibitors. Here, we extend our mode-of-action analyses and report that AIC246 blocks viral replication without inhibiting the synthesis of progeny HCMV DNA or viral proteins. The genotyping of mutant viruses that escaped AIC246 inhibition uncovered distinct point mutations in the UL56 subunit of the viral terminase complex. Marker transfer analyses confirmed that these mutations were sufficient to mediate AIC246 resistance. The mapping of drug resistance to open reading frame UL56 suggests that viral DNA processing and/or packaging is targeted by AIC246. In line with this, we demonstrate that AIC246 affects the formation of proper unit-length genomes from viral DNA concatemers and interferes with virion maturation. However, since AIC246-resistant viruses do not exhibit cross-resistance to previously published terminase inhibitors, our data suggest that AIC246 interferes with HCMV DNA cleavage/packaging via a molecular mechanism that is distinct from that of other compound classes known to target the viral terminase. PMID:21752907

  15. The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase.

    Science.gov (United States)

    Goldner, Thomas; Hewlett, Guy; Ettischer, Nicole; Ruebsamen-Schaeff, Helga; Zimmermann, Holger; Lischka, Peter

    2011-10-01

    Human cytomegalovirus (HCMV) remains the leading viral cause of birth defects and life-threatening disease in transplant recipients. All approved antiviral drugs target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Attempts to discover improved anti-HCMV drugs led to the identification of the small-molecular-weight compound AIC246 (Letermovir). AIC246 exhibits outstanding anti-HCMV activity in vitro and in vivo and currently is undergoing a clinical phase IIb trial. The initial mode-of-action studies suggested that the drug acts late in the HCMV replication cycle via a mechanism distinct from that of polymerase inhibitors. Here, we extend our mode-of-action analyses and report that AIC246 blocks viral replication without inhibiting the synthesis of progeny HCMV DNA or viral proteins. The genotyping of mutant viruses that escaped AIC246 inhibition uncovered distinct point mutations in the UL56 subunit of the viral terminase complex. Marker transfer analyses confirmed that these mutations were sufficient to mediate AIC246 resistance. The mapping of drug resistance to open reading frame UL56 suggests that viral DNA processing and/or packaging is targeted by AIC246. In line with this, we demonstrate that AIC246 affects the formation of proper unit-length genomes from viral DNA concatemers and interferes with virion maturation. However, since AIC246-resistant viruses do not exhibit cross-resistance to previously published terminase inhibitors, our data suggest that AIC246 interferes with HCMV DNA cleavage/packaging via a molecular mechanism that is distinct from that of other compound classes known to target the viral terminase.

  16. Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis

    OpenAIRE

    Cheuvart, Brigitte; Neuzil, Kathleen M; Steele, A Duncan; Cunliffe, Nigel; Madhi, Shabir A; Karkada, Naveen; Han, Htay Htay; Vinals, Carla

    2013-01-01

    Clinical trials of the human rotavirus vaccine Rotarix? (RV1) have demonstrated significant reductions in severe rotavirus gastroenteritis (RVGE) in children worldwide. However, no correlate of vaccine efficacy (VE) has yet been established. This paper presents 2 analyses which aimed to investigate whether serum anti-RV IgA measured by ELISA 1 or 2 mo post-vaccination can serve as a correlate of efficacy against RVGE: (1) In a large Phase III efficacy trial (Rota-037), the Prentice criteria f...

  17. Pemasaran ViralViral Marketing

    OpenAIRE

    Situmorang, James Rianto

    2010-01-01

    Viral marketing is an extremely powerful and effective form of internet marketing. Itis a new form of word-of-mouth through internet. In viral marketing, someone passeson a marketing message to someone else and so on. Viral marketing proposes thatmessages can be rapidly disseminated from consumer to consumer leading to largescale market acceptance. The analogy of a virus is used to described the exponentialdiffusion of information in an electronic environment and should not be confusedwith th...

  18. Respiratory Syncytial Virus; Anti-viral immunity in humans and macaques.

    NARCIS (Netherlands)

    L. de Waal (Leon)

    2003-01-01

    textabstractThe results presented in this thesis show that hRSV infection in humans results in a multifaceted immune response, which cannot be described as purely Th1- or Th2-like. However, the observed higher level of IL-13 producing hRSV-specific T cells in infants hospitalized with severe hRSV

  19. Viral gene expression, antibody production and immune complex formation in human immunodeficiency virus infection

    NARCIS (Netherlands)

    Lange, J. M.; Paul, D. A.; de Wolf, F.; Coutinho, R. A.; Goudsmit, J.

    1987-01-01

    Human immunodeficiency virus (HIV) antigen (HIV-Ag) in polyethylene glycol (PEG) precipitates and supernatants and HIV antibodies (HIV-Ab) to core and envelope antigens were studied in serial serum samples of three HIV-Ab seroconverters and 11 HIV-Ab seropositive men with a mean follow-up time of

  20. Autologous neutralizing humoral immunity and evolution of the viral envelope in the course of subtype B human immunodeficiency virus type 1 infection

    NARCIS (Netherlands)

    Bunnik, Evelien M.; Pisas, Linaida; van Nuenen, Ad C.; Schuitemaker, Hanneke

    2008-01-01

    Most human immunodeficiency virus type 1 (HIV-1)-infected individuals develop an HIV-specific neutralizing antibody (NAb) response that selects for escape variants of the virus. Here, we studied autologous NAb responses in five typical CCR5-using progressors in relation to viral NAb escape and

  1. Gastroenteritis and the novel picornaviruses aichi virus, cosavirus, saffold virus, and salivirus in young children.

    Science.gov (United States)

    Nielsen, Alex Christian Yde; Gyhrs, Mette Louise; Nielsen, Lars Peter; Pedersen, Court; Böttiger, Blenda

    2013-07-01

    During the last few years many new human picornaviruses have been discovered due to advances in metagenomics and other molecular biological approaches. The clinical significance and the occurrence are only sparsely described. To determine the epidemiology and clinical significance of infections with the novel human picornaviruses, aichi virus, cosavirus, salivirus, and saffold virus in infants in Denmark. We tested 1393 stool samples from a birth cohort of 454 children for these viruses. Samples were collected at ages 6, 10 and 15 months, and at episodes of gastroenteritis. Samples were tested by real-time reverse-transcriptase polymerase chain reaction assays. Each study participant had a diary, where the parents reported episodes of disease, including gastroenteritis. Aichi virus, salivirus and saffold virus were detected in 6, 9 and 38 of the children, respectively, but cosavirus was not detected in any of the children. There was a clear seasonal variation with most infections occurring in autumn and winter. A statistically significant association between the findings of salivirus and gastrointestinal disease was demonstrated. There was no association between gastrointestinal disease and the presence of aichi virus or saffold virus. The newly discovered human picornaviruses aichi virus, saffold virus, and salivirus are circulating in Danish children, with the most common being saffold virus. Saffold virus was seen almost exclusively in the autumn and winter period. Salivirus was the only virus, which was significantly associated with gastroenteritis, although the number of positive samples was rather low. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Ecological Interactions between Humans, Wildlife Viral Reservoirs, and Key Environmental Drivers of Hantaan Virus Transmission

    Directory of Open Access Journals (Sweden)

    Xin Tong

    2017-10-01

    Full Text Available The occurrence and transmission of hemorrhagic fever with renal syndrome (HFRS are closely related to environmental variability, so it is essential to clarify the complex relationships among the environment, hantavirus transmission, and the population dynamics of its wildlife hosts. Tian et al. analyzed a large, long-term dataset describing the circulation of hantavirus in rodents and its spillover into humans. Their article incorporates several mathematical models and argues that the interaction between environmental and human behavioral factors drives the observed seasonality and interannual variations in important zoonotic diseases. The ecological cascade effect of a drought in 2002 is highlighted, and the role of seasonality in agricultural activity is emphasized in that study.

  3. Synthetic protocells interact with viral nanomachinery and inactivate pathogenic human virus.

    Directory of Open Access Journals (Sweden)

    Matteo Porotto

    Full Text Available We present a new antiviral strategy and research tool that could be applied to a wide range of enveloped viruses that infect human beings via membrane fusion. We test this strategy on two emerging zoonotic henipaviruses that cause fatal encephalitis in humans, Nipah (NiV and Hendra (HeV viruses. In the new approach, artificial cell-like particles (protocells presenting membrane receptors in a biomimetic manner were developed and found to attract and inactivate henipavirus envelope glycoprotein pseudovirus particles, preventing infection. The protocells do not accumulate virus during the inactivation process. The use of protocells that interact with, but do not accumulate, viruses may provide significant advantages over current antiviral drugs, and this general approach may have wide potential for antiviral development.

  4. Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus......Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental...... factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...

  5. Differential decomposition of bacterial and viral fecal indicators in common human pollution types.

    Science.gov (United States)

    Wanjugi, Pauline; Sivaganesan, Mano; Korajkic, Asja; Kelty, Catherine A; McMinn, Brian; Ulrich, Robert; Harwood, Valerie J; Shanks, Orin C

    2016-11-15

    Understanding the decomposition of microorganisms associated with different human fecal pollution types is necessary for proper implementation of many water quality management practices, as well as predicting associated public health risks. Here, the decomposition of select cultivated and molecular indicators of fecal pollution originating from fresh human feces, septage, and primary effluent sewage in a subtropical marine environment was assessed over a six day period with an emphasis on the influence of ambient sunlight and indigenous microbiota. Ambient water mixed with each fecal pollution type was placed in dialysis bags and incubated in situ in a submersible aquatic mesocosm. Genetic and cultivated fecal indicators including fecal indicator bacteria (enterococci, E. coli, and Bacteroidales), coliphage (somatic and F+), Bacteroides fragilis phage (GB-124), and human-associated genetic indicators (HF183/BacR287 and HumM2) were measured in each sample. Simple linear regression assessing treatment trends in each pollution type over time showed significant decay (p ≤ 0.05) in most treatments for feces and sewage (27/28 and 32/40, respectively), compared to septage (6/26). A two-way analysis of variance of log10 reduction values for sewage and feces experiments indicated that treatments differentially impact survival of cultivated bacteria, cultivated phage, and genetic indicators. Findings suggest that sunlight is critical for phage decay, and indigenous microbiota play a lesser role. For bacterial cultivated and genetic indicators, the influence of indigenous microbiota varied by pollution type. This study offers new insights on the decomposition of common human fecal pollution types in a subtropical marine environment with important implications for water quality management applications. Published by Elsevier Ltd.

  6. [Viral infection of herpes simplex, Epstein-Barr, varicela zoster, human papilloma, cytomegalovirus, or adenovirus are not related to sinonasal adenocarcinomas].

    Science.gov (United States)

    Pérez Escuredo, Jhudit; Llorente, José Luis; Melón, Santiago; de Oña, María; García Martínez, Jorge; Alvarez Marcos, César; Hermsen, Mario

    2007-01-01

    Several types of virus have been implicated in the development of head and neck tumors. However, until now sinonasal adenocarcinomas (ACN) have not been studied. The aim of this study is to screen a series of ACN for the presence of a number of viruses known to play a role in cancer. Viral DNA sequences of herpes simplex virus, Epstein-Barr, varicela zoster, human papilloma, cytomegalovirus, and adenovirus were analysed by PCR in 37 primary ACN. Three tumors (8.1%) were positive for Epstein-Barr virus and 1 case (2.7%) for cytomegalovirus. Viral infections do not seem to play a role in the etiology of ACN.

  7. Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States

    Science.gov (United States)

    Payne, Daniel C.; Currier, Rebecca L.; Staat, Mary A.; Sahni, Leila C.; Selvarangan, Rangaraj; Halasa, Natasha B.; Englund, Janet A.; Weinberg, Geoffrey A.; Boom, Julie A.; Szilagyi, Peter G.; Klein, Eileen J.; Chappell, James; Harrison, Christopher J.; Davidson, Barbara S.; Mijatovic-Rustempasic, Slavica; Moffatt, Mary D.; McNeal, Monica; Wikswo, Mary; Bowen, Michael D.; Morrow, Ardythe L.; Parashar, Umesh D.

    2016-01-01

    IMPORTANCE A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus. OBJECTIVE We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTS Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURES Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test–positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis. RESULTS One (0.5%) of 189 rotavirus test–positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower

  8. Rice water in treatment of infantile gastroenteritis.

    Science.gov (United States)

    Wong, H B

    1981-07-11

    In Singapore the World Health Organization's (WHO's) oral electrolyte solution for the treatment of infantile gastroenteritis has been used for 6 years and rice water has been used for 8 years. The rice water is the water used in preparing boiled rice or congee and is a slightly starchy solution. As the impression was that rice water was as effective as or even better than the oral electrolyte solution, a trial was conducted of the 2 solutions in babies with gastroenteritis admitted to the Department of Pediatrics of the National University of Singapore. Alternate cases were assigned consecutively to the oral electrolyte solution or to rice water. There were 63 patients on oral electrolyte and 67 on rice water. Milk was totally withdrawn for 24 hours after admission and the babies were put on 1 or the other oral solution. Intravenous 3.75% glucose and 0.23% saline was given at the same time to babies considered to be more dehydrated. On day 2, quarter strength powdered milk was given, followed by half strength on day 3, three-quarters strength on day 4, and full strength on day 5. Electrolyte and urea values were compared, both for "drip" versus "no drip" within oral treatment groups and between electrolyte solution and rice water groups (20 comparisons altogether). There were only 3 significant differences, and these might be explained by the intravenous drip and by the better water absorption from rice water than from the oral electrolyte solution. The most obvious difference in the 2 groups was in the effect on diarrhea (stools/day). Rice water cut down the number of stools more effectively than did oral electrolyte solution. No patient died, and there were no pathological sequelae in any of the 130 patients. Rice water can be tried as a more practical alternative to oral electrolyte solutions since there are problems with providing oral elecrolyte solutions to all babies with diarrhea in the developing countries and ensuring sterility.

  9. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  10. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  11. Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis

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    Thong Van Nguyen

    2015-01-01

    Interpretation: Our study based on the pathological examination demonstrated that the rubella virus infection occurred via systemic organs of human fetuses. This fact was confirmed by immunohistochemistry and direct detection of viral RNA in multiple organs. To the best of our knowledge, this study is the first report demonstrating that the rubella virus infection occurred via systemic organs of the human body. Importantly, virus infection of the ciliary body could play an important role in cataractogenesis.

  12. Clinical characteristics and viral load of respiratory syncytial virus and human metapneumovirus in children hospitaled for acute lower respiratory tract infection.

    Science.gov (United States)

    Yan, Xiao-Li; Li, Yu-Ning; Tang, Yi-Jie; Xie, Zhi-Ping; Gao, Han-Chun; Yang, Xue-Mei; Li, Yu-Mei; Liu, Li-Jun; Duan, Zhao-Jun

    2017-04-01

    Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well-defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty-seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real-time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co-infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89:589-597, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Viral load and short-term natural history of type-specific oncogenic human papillomavirus infections in a high-risk cohort of midadult women.

    Science.gov (United States)

    Winer, Rachel L; Xi, Long Fu; Shen, Zhenping; Stern, Joshua E; Newman, Laura; Feng, Qinghua; Hughes, James P; Koutsky, Laura A

    2014-04-15

    Oncogenic human papillomavirus (HPV) viral load may inform the origin of newly detected infections and characterize oncogenic HPV natural history in midadult women. From 2007 to 2011, we enrolled 521 25-65-year-old-female online daters and followed them triannually with mailed health and sexual behavior questionnaires and kits for self-sampling for PCR-based HPV DNA testing. Samples from oncogenic HPV positive women were selected for type-specific DNA load testing by real-time PCR with adjustment for cellularity. Linear or logistic regression models were used to evaluate relationships between viral levels, health and sexual behavior, and longitudinal oncogenic HPV detection. Type-specific viral levels were borderline significantly higher in oncogenic HPV infections that were prevalent versus newly detected (p = 0.092), but levels in newly detected infections were higher than in infections redetected after intercurrent negativity (p detected intermittently, the likelihood of persistent (OR = 4.31, 95% CI: 2.20-8.45) or single-time (OR = 1.32, 95% CI: 1.03-1.71) detection increased per 1-unit increase in baseline log10 viral load. Viral load differences between redetected and newly detected infections suggest a portion of new detections were due to new acquisition, although report of recent new sex partners (a potential marker of new infection) was not predictive of viral load; oncogenic HPV infections in midadult women with new partners likely represent a mix of new acquisition and reactivation or intermittent detection of previous infection. Intermittent detection was characterized by low viral levels, suggesting that intermittent detection of persisting oncogenic HPV infection may be of limited clinical significance. © 2013 UICC.

  14. A novel highly potent therapeutic antibody neutralizes multiple human chemokines and mimics viral immune modulation.

    Science.gov (United States)

    Scalley-Kim, Michelle L; Hess, Bruce W; Kelly, Ryan L; Krostag, Anne-Rachel F; Lustig, Kurt H; Marken, John S; Ovendale, Pamela J; Posey, Aaron R; Smolak, Pamela J; Taylor, Janelle D L; Wood, C L; Bienvenue, David L; Probst, Peter; Salmon, Ruth A; Allison, Daniel S; Foy, Teresa M; Raport, Carol J

    2012-01-01

    Chemokines play a key role in leukocyte recruitment during inflammation and are implicated in the pathogenesis of a number of autoimmune diseases. As such, inhibiting chemokine signaling has been of keen interest for the development of therapeutic agents. This endeavor, however, has been hampered due to complexities in the chemokine system. Many chemokines have been shown to signal through multiple receptors and, conversely, most chemokine receptors bind to more than one chemokine. One approach to overcoming this complexity is to develop a single therapeutic agent that binds and inactivates multiple chemokines, similar to an immune evasion strategy utilized by a number of viruses. Here, we describe the development and characterization of a novel therapeutic antibody that targets a subset of human CC chemokines, specifically CCL3, CCL4, and CCL5, involved in chronic inflammatory diseases. Using a sequential immunization approach, followed by humanization and phage display affinity maturation, a therapeutic antibody was developed that displays high binding affinity towards the three targeted chemokines. In vitro, this antibody potently inhibits chemotaxis and chemokine-mediated signaling through CCR1 and CCR5, primary chemokine receptors for the targeted chemokines. Furthermore, we have demonstrated in vivo efficacy of the antibody in a SCID-hu mouse model of skin leukocyte migration, thus confirming its potential as a novel therapeutic chemokine antagonist. We anticipate that this antibody will have broad therapeutic utility in the treatment of a number of autoimmune diseases due to its ability to simultaneously neutralize multiple chemokines implicated in disease pathogenesis.

  15. Survey on the Ability of Wolbachia to Control Human Viral, Protozoan, and Filarial Disease Pathogens

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    Garedaghi Yagoob

    2014-04-01

    Full Text Available Objective: Most human filarial nematode parasites and arthropods are hosts for a bacterial endosymbiont, Wolbachia. In filariasis, Wolbachia are required for normal development, fertility, and survival. However, in arthropods, Wolbachia are largely parasitic and can influence development and reproduction, but are generally not required for host survival. Materials and Methods: Due to their obligate nature in filarial parasites, Wolbachia have been a target for drug discovery initiatives using several approaches including diversity and focused library screening and genomic sequence analysis. Results: In vitro and in vivo anti-Wolbachia antibiotic treatments have been shown to have adulticidal activity, a long sought goal of filarial parasite drug discovery. In mosquitoes, it has been shown that the presence of Wolbachia can inhibit the transmission of certain viruses, such as dengue, chikungunya, yellow fever, West Nile, as well as the infectivity of the malaria-causing protozoan, Plasmodium and filarial nematodes. Conclusion: Wolbachia can cause a form of conditional sterility that can be used to suppress populations of mosquitoes and additional medically important insects. Thus, Wolbachia, a pandemic endosymbiont, offers great potential for elimination of a wide-variety of devastating human diseases.

  16. IMMUNE INHIBITION OF VIRUS RELEASE FROM HUMAN AND NONHUMAN CELLS BY ANTIBODY TO VIRAL AND HOST-CELL DETERMINANTS

    NARCIS (Netherlands)

    SHARIFF, DM; DESPERBASQUES, M; BILLSTROM, M; GEERLIGS, HJ; WELLING, GW; WELLINGWESTER, S; BUCHAN, A; SKINNER, GRB

    1991-01-01

    Immune inhibition of release of the DNA virues, herpes simplex virus types 1 and 2 and pseudorabies virus by anti-viral and anti-host cell sera occurred while two RNA viruses, influenza and encephalomyocarditis, were inhibited only by anti-viral sera (not anti-host cell sera). Simian virus 40 and

  17. Human immunodeficiency virus integrase protein requires a subterminal position of its viral DNA recognition sequence for efficient cleavage

    NARCIS (Netherlands)

    C. Vink (Cornelis); D.C. van Gent (Dik); Y. Elgersma (Ype); R.H. Plassterk

    1991-01-01

    textabstractRetroviral integration requires cis-acting sequences at the termini of linear double-stranded viral DNA and a product of the retroviral pol gene, the integrase protein (IN). IN is required and sufficient for generation of recessed 3' termini of the viral DNA (the first

  18. Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling.

    Science.gov (United States)

    Bristol, Molly L; Das, Dipon; Morgan, Iain M

    2017-09-21

    Human papillomaviruses (HPV) require the activation of the DNA damage response (DDR) in order to undergo a successful life cycle. This activation presents a challenge for the virus and the infected cell: how does viral and host replication proceed in the presence of a DDR that ordinarily arrests replication; and how do HPV16 infected cells retain the ability to proliferate in the presence of a DDR that ordinarily arrests the cell cycle? This raises a further question: why do HPV activate the DDR? The answers to these questions are only partially understood; a full understanding could identify novel therapeutic strategies to target HPV cancers. Here, we propose that the rapid replication of an 8 kb double stranded circular genome during infection creates aberrant DNA structures that attract and activate DDR proteins. Therefore, HPV replication in the presence of an active DDR is a necessity for a successful viral life cycle in order to resolve these DNA structures on viral genomes; without an active DDR, successful replication of the viral genome would not proceed. We discuss the essential role of TopBP1 in this process and also how viral and cellular replication proceeds in HPV infected cells in the presence of DDR signals.

  19. Adaptive memory of human NK-like CD8+ T-cells to ageing, and viral and tumor antigens

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    MARIA LUISA PITA-LOPEZ

    2016-12-01

    Full Text Available Human NK-like CD8+ T-cells are singular T-cells that express both T and NK cell markers such as CD56; their frequencies depend on their differentiation and activation during their lifetime. There is evidence of the presence of these innate CD8+ T-cells in the human umbilical cord, highlighting the necessity of investigating whether the NK-like CD8+ T-cells arise in the early stages of life (gestation. Based on the presence of cell surface markers, these cells have also been referred to as CD8+KIR+ T-cells, innate CD8+ T-cells, CD8+CD28−KIR+ T-cells or NKT-like CD8+CD56+ cells. However, the functional and co-signaling significance of these NK cell receptors on NK-like CD8+ T-cells is less clear. Also, the diverse array of co-stimulatory and co-inhibitory receptors are spatially and temporally regulated and may have distinct overlapping functions on NK-like CD8+ T-cell priming, activation, differentiation, and memory responses associated with different cell phenotypes. Currently, there is no consensus regarding the functional properties and phenotypic characterization of human NK-like CD8+ T-cells. Environmental factors, such as aging, autoimmunity, inflammation, viral antigen re-exposure or the presence of persistent tumor antigens have been shown to allow differentiation (adaptation of the NK-like CD8+ T-cells; the elucidation of this differentiation process and a greater understanding of the characteristics of these cells could be important for their eventual in potential therapeutic applications aimed at improving protective immunity. This review will attempt to elucidate a understanding of the characteristics of these cells with the goal towards their eventual use in potential therapeutic applications aimed at improving protective immunity.

  20. Human Parechovirus 3: The Most Common Viral Cause of Meningoencephalitis in Young Infants.

    Science.gov (United States)

    Renaud, Christian; Harrison, Christopher J

    2015-09-01

    Human parechoviruses (HPeVs) were initially classified as echoviruses. HPeVs occur worldwide, comprising up to 17 genotypes. HPeV1 and HPeV3 are most common. Clinical disease varies somewhat among genotypes. HPeV1 causes mostly gastrointestinal infections. HPeV3's prominence is due to its causing sepsis syndromes and central nervous system (CNS) infections in young infants. Currently, HPeV3 is the most common single cause of aseptic meningitis/meningoencephalitis in infants less than 90 days old in North America, usually with biannual summer-fall seasonality. HPeV3 CNS infections usually lack cerebrospinal fluid pleocytosis. Mortality and sequelae are uncommon, usually accompanying initially severe or neurologically complicated acute illnesses. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Human Metapneumovirus and Other Respiratory Viral Infections during Pregnancy and Birth, Nepal.

    Science.gov (United States)

    Lenahan, Jennifer L; Englund, Janet A; Katz, Joanne; Kuypers, Jane; Wald, Anna; Magaret, Amalia; Tielsch, James M; Khatry, Subarna K; LeClerq, Stephen C; Shrestha, Laxman; Steinhoff, Mark C; Chu, Helen Y

    2017-08-01

    Human metapneumovirus (HMPV) is a respiratory virus that can cause severe lower respiratory tract disease and even death, primarily in young children. The incidence and characteristics of HMPV have not been well described in pregnant women. As part of a trial of maternal influenza immunization in rural southern Nepal, we conducted prospective, longitudinal, home-based active surveillance for febrile respiratory illness during pregnancy through 6 months postpartum. During 2011-2014, HMPV was detected in 55 of 3,693 women (16.4 cases/1,000 person-years). Twenty-five women were infected with HMPV during pregnancy, compared with 98 pregnant women who contracted rhinovirus and 7 who contracted respiratory syncytial virus. Women with HMPV during pregnancy had an increased risk of giving birth to infants who were small for gestational age. An intervention to reduce HMPV febrile respiratory illness in pregnant women may have the potential to decrease risk of adverse birth outcomes in developing countries.

  2. The Revolution in Viral Genomics as Exemplified by the Bioinformatic Analysis of Human Adenoviruses

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    Sarah Torres

    2010-06-01

    Full Text Available Over the past 30 years, genomic and bioinformatic analysis of human adenoviruses has been achieved using a variety of DNA sequencing methods; initially with the use of restriction enzymes and more currently with the use of the GS FLX pyrosequencing technology. Following the conception of DNA sequencing in the 1970s, analysis of adenoviruses has evolved from 100 base pair mRNA fragments to entire genomes. Comparative genomics of adenoviruses made its debut in 1984 when nucleotides and amino acids of coding sequences within the hexon genes of two human adenoviruses (HAdV, HAdV–C2 and HAdV–C5, were compared and analyzed. It was determined that there were three different zones (1-393, 394-1410, 1411-2910 within the hexon gene, of which HAdV–C2 and HAdV–C5 shared zones 1 and 3 with 95% and 89.5% nucleotide identity, respectively. In 1992, HAdV-C5 became the first adenovirus genome to be fully sequenced using the Sanger method. Over the next seven years, whole genome analysis and characterization was completed using bioinformatic tools such as blastn, tblastx, ClustalV and FASTA, in order to determine key proteins in species HAdV-A through HAdV-F. The bioinformatic revolution was initiated with the introduction of a novel species, HAdV-G, that was typed and named by the use of whole genome sequencing and phylogenetics as opposed to traditional serology. HAdV bioinformatics will continue to advance as the latest sequencing technology enables scientists to add to and expand the resource databases. As a result of these advancements, how novel HAdVs are typed has changed. Bioinformatic analysis has become the revolutionary tool that has significantly accelerated the in-depth study of HAdV microevolution through comparative genomics.

  3. Viral Hepatitis

    Science.gov (United States)

    ... Us FAQs Ask a Question Toll Free Numbers Homeless Veterans Chat VA » Health Care » Viral Hepatitis » Veterans and ... Vet Centers) War Related Illness & Injury Study Center Homeless Veterans Returning Service Members Rural Veterans Seniors & Aging Veterans ...

  4. Viral single-strand DNA induces p53-dependent apoptosis in human embryonic stem cells.

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    Matthew L Hirsch

    Full Text Available Human embryonic stem cells (hESCs are primed for rapid apoptosis following mild forms of genotoxic stress. A natural form of such cellular stress occurs in response to recombinant adeno-associated virus (rAAV single-strand DNA genomes, which exploit the host DNA damage response for replication and genome persistence. Herein, we discovered a unique DNA damage response induced by rAAV transduction specific to pluripotent hESCs. Within hours following rAAV transduction, host DNA damage signaling was elicited as measured by increased gamma-H2AX, ser15-p53 phosphorylation, and subsequent p53-dependent transcriptional activation. Nucleotide incorporation assays demonstrated that rAAV transduced cells accumulated in early S-phase followed by the induction of apoptosis. This lethal signaling sequalae required p53 in a manner independent of transcriptional induction of Puma, Bax and Bcl-2 and was not evident in cells differentiated towards a neural lineage. Consistent with a lethal DNA damage response induced upon rAAV transduction of hESCs, empty AAV protein capsids demonstrated no toxicity. In contrast, DNA microinjections demonstrated that the minimal AAV origin of replication and, in particular, a 40 nucleotide G-rich tetrad repeat sequence, was sufficient for hESC apoptosis. Our data support a model in which rAAV transduction of hESCs induces a p53-dependent lethal response that is elicited by a telomeric sequence within the AAV origin of replication.

  5. Direct binding of retromer to human papillomavirus type 16 minor capsid protein L2 mediates endosome exit during viral infection.

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    Andreea Popa

    2015-02-01

    Full Text Available Trafficking of human papillomaviruses to the Golgi apparatus during virus entry requires retromer, an endosomal coat protein complex that mediates the vesicular transport of cellular transmembrane proteins from the endosome to the Golgi apparatus or the plasma membrane. Here we show that the HPV16 L2 minor capsid protein is a retromer cargo, even though L2 is not a transmembrane protein. We show that direct binding of retromer to a conserved sequence in the carboxy-terminus of L2 is required for exit of L2 from the early endosome and delivery to the trans-Golgi network during virus entry. This binding site is different from known retromer binding motifs and can be replaced by a sorting signal from a cellular retromer cargo. Thus, HPV16 is an unconventional particulate retromer cargo, and retromer binding initiates retrograde transport of viral components from the endosome to the trans-Golgi network during virus entry. We propose that the carboxy-terminal segment of L2 protein protrudes through the endosomal membrane and is accessed by retromer in the cytoplasm.

  6. Impacts of Humanized Mouse Models on the Investigation of HIV-1 Infection: Illuminating the Roles of Viral Accessory Proteins in Vivo

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    Eri Yamada

    2015-03-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 encodes four accessory genes: vif, vpu, vpr, and nef. Recent investigations using in vitro cell culture systems have shed light on the roles of these HIV-1 accessory proteins, Vif, Vpr, Vpu, and Nef, in counteracting, modulating, and evading various cellular factors that are responsible for anti-HIV-1 intrinsic immunity. However, since humans are the exclusive target for HIV-1 infection, conventional animal models are incapable of mimicking the dynamics of HIV-1 infection in vivo. Moreover, the effects of HIV-1 accessory proteins on viral infection in vivo remain unclear. To elucidate the roles of HIV-1 accessory proteins in the dynamics of viral infection in vivo, humanized mouse models, in which the mice are xenotransplanted with human hematopoietic stem cells, has been utilized. This review describes the current knowledge of the roles of HIV-1 accessory proteins in viral infection, replication, and pathogenicity in vivo, which are revealed by the studies using humanized mouse models.

  7. Cross-presentation of viral antigens in dribbles leads to efficient activation of virus-specific human memory T cells.

    Science.gov (United States)

    Ye, Wei; Xing, Yun; Paustian, Christopher; van de Ven, Rieneke; Moudgil, Tarsem; Hilton, Traci L; Fox, Bernard A; Urba, Walter J; Zhao, Wei; Hu, Hong-Ming

    2014-04-16

    Autophagy regulates innate and adaptive immune responses to pathogens and tumors. We have reported that autophagosomes derived from tumor cells after proteasome inhibition, DRibbles (Defective ribosomal products in blebs), were excellent sources of antigens for efficient cross priming of tumor-specific CD8⁺ T cells, which mediated regression of established tumors in mice. But the activity of DRibbles in human has not been reported. DRibbles or cell lysates derived from HEK293T or UbiLT3 cell lines expressing cytomegalovirus (CMV) pp65 protein or transfected with a plasmid encoding dominant HLA-A2 restricted CMV, Epstein-Barr virus (EBV), and Influenza (Flu) epitopes (CEF) were loaded onto human monocytes or PBMCs and the response of human CMV pp65 or CEF antigen-specific CD4⁺ and CD8⁺ memory T cells was detected by intracellular staining. The effect of cytokines (GM-CSF, IL-4, IL-12, TNF-α, IFN-α and IFN-γ) TLR agonists (Lipopolysaccharide, Polyinosinic-polycytidylic acid (poly(I:C), M52-CpG, R848, TLR2 ligand) and CD40 ligand on the cross-presentation of antigens contained in DRibbles or cell lysates was explored. In this study we showed that purified monocytes, or human PBMCs, loaded with DRibbles isolated from cells expressing CMV or CEF epitopes, could activate CMV- or CEF-specific memory T cells. DRibbles were significantly more efficient at stimulating CD8⁺ memory T cells compared to cell lysates expressing the same antigenic epitopes. We optimized the conditions for T-cell activation and IFN-γ production following direct loading of DRibbles onto PBMCs. We found that the addition of Poly(I:C), CD40 ligand, and GM-CSF to the PBMCs together with DRibbles significantly increased the level of CD8⁺ T cell responses. DRibbles containing specific viral antigens are an efficient ex vivo activator of human antigen-specific memory T cells specific for those antigens. This function could be enhanced by combining with Poly(I:C), CD40 ligand, and GM

  8. Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study.

    Science.gov (United States)

    Van der Wielen, Marie; Giaquinto, Carlo; Gothefors, Leif; Huelsse, Christel; Huet, Frédéric; Littmann, Martina; Maxwell, Melanie; Talayero, José M P; Todd, Peter; Vila, Miguel T; Cantarutti, Luigi; Van Damme, Pierre

    2010-03-15

    Rotavirus is the leading cause of acute gastroenteritis (AGE) and the most frequent cause of severe diarrhoea in children aged less than 5 years. Although the epidemiology of rotavirus gastroenteritis (RVGE) is well documented, there are few data on the impact of RVGE on the families of affected children. Data associated with the burden of RVGE, including number of working days lost, levels of parental stress, the need for alternative childcare arrangements and additional nappies used, were extracted from questionnaires completed by parents of children participating in a prospective, multicentre, observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in public health and society, REVEAL), conducted during 2004-2005 in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom to estimate the incidence of RVGE in children aged less than 5 years seeking medical care as a result of AGE. 1102 children with RVGE were included in the present analysis. The proportion of RVGE cases that required at least one parent or other person to be absent from work was 39%-91% in the hospital setting, 44%-64% in the emergency department, and 20%-64% in primary care. Self-reported levels of parental stress were generally high (mean stress levels, > or = 5 on a 10-point visual analogue scale). Additional childcare arrangements were required in up to 21% of RVGE episodes. The mean number of nappies used per day during RVGE episodes was approximately double that used when the child was not ill. Paediatric RVGE cases cause disruption to families and parental stress. The burden of RVGE on children and their families could be substantially reduced by routine rotavirus vaccination of infants.

  9. Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study

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    Talayero José MP

    2010-03-01

    Full Text Available Abstract Background Rotavirus is the leading cause of acute gastroenteritis (AGE and the most frequent cause of severe diarrhoea in children aged less than 5 years. Although the epidemiology of rotavirus gastroenteritis (RVGE is well documented, there are few data on the impact of RVGE on the families of affected children. Methods Data associated with the burden of RVGE, including number of working days lost, levels of parental stress, the need for alternative childcare arrangements and additional nappies used, were extracted from questionnaires completed by parents of children participating in a prospective, multicentre, observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in public health and society, REVEAL, conducted during 2004-2005 in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom to estimate the incidence of RVGE in children aged less than 5 years seeking medical care as a result of AGE. Results 1102 children with RVGE were included in the present analysis. The proportion of RVGE cases that required at least one parent or other person to be absent from work was 39%-91% in the hospital setting, 44%-64% in the emergency department, and 20%-64% in primary care. Self-reported levels of parental stress were generally high (mean stress levels, ≥ 5 on a 10-point visual analogue scale. Additional childcare arrangements were required in up to 21% of RVGE episodes. The mean number of nappies used per day during RVGE episodes was approximately double that used when the child was not ill. Conclusions Paediatric RVGE cases cause disruption to families and parental stress. The burden of RVGE on children and their families could be substantially reduced by routine rotavirus vaccination of infants.

  10. Major Histocompatibility Complex Class II Transactivator CIITA Is a Viral Restriction Factor That Targets Human T-Cell Lymphotropic Virus Type 1 Tax-1 Function and Inhibits Viral Replication▿

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    Tosi, Giovanna; Forlani, Greta; Andresen, Vibeke; Turci, Marco; Bertazzoni, Umberto; Franchini, Genoveffa; Poli, Guido; Accolla, Roberto S.

    2011-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of an aggressive malignancy of CD4+ T lymphocytes. Since the viral transactivator Tax-1 is a major player in T-cell transformation, targeting Tax-1 protein is regarded as a possible strategy to arrest viral replication and to counteract neoplastic transformation. We demonstrate that CIITA, the master regulator of major histocompatibility complex class II gene transcription, inhibits HTLV-1 replication by blocking the transactivating function of Tax-1 both when exogenously transfected in 293T cells and when endogenously expressed by a subset of U937 promonocytic cells. Tax-1 and CIITA physically interact in vivo via the first 108 amino acids of Tax-1 and two CIITA adjacent regions (amino acids 1 to 252 and 253 to 410). Interestingly, only CIITA 1-252 mediated Tax-1 inhibition, in agreement with the fact that CIITA residues from positions 64 to 124 were required to block Tax-1 transactivation. CIITA inhibitory action on Tax-1 correlated with the nuclear localization of CIITA and was independent of the transcription factor NF-YB, previously involved in CIITA-mediated inhibition of Tax-2 of HTLV-2. Instead, CIITA severely impaired the physical and functional interaction of Tax-1 with the cellular coactivators p300/CBP-associated factor (PCAF), cyclic AMP-responsive element binding protein (CREB), and activating transcription factor 1 (ATF1), which are required for the optimal activation of HTLV-1 promoter. Accordingly, the overexpression of PCAF, CREB, and ATF1 restored Tax-1-dependent transactivation of the viral long-terminal-repeat promoter inhibited by CIITA. These findings strongly support our original observation that CIITA, beside increasing the antigen-presenting function for pathogen antigens, acts as an endogenous restriction factor against human retroviruses by blocking virus replication and spreading. PMID:21813598

  11. Major histocompatibility complex class II transactivator CIITA is a viral restriction factor that targets human T-cell lymphotropic virus type 1 Tax-1 function and inhibits viral replication.

    Science.gov (United States)

    Tosi, Giovanna; Forlani, Greta; Andresen, Vibeke; Turci, Marco; Bertazzoni, Umberto; Franchini, Genoveffa; Poli, Guido; Accolla, Roberto S

    2011-10-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of an aggressive malignancy of CD4+ T lymphocytes. Since the viral transactivator Tax-1 is a major player in T-cell transformation, targeting Tax-1 protein is regarded as a possible strategy to arrest viral replication and to counteract neoplastic transformation. We demonstrate that CIITA, the master regulator of major histocompatibility complex class II gene transcription, inhibits HTLV-1 replication by blocking the transactivating function of Tax-1 both when exogenously transfected in 293T cells and when endogenously expressed by a subset of U937 promonocytic cells. Tax-1 and CIITA physically interact in vivo via the first 108 amino acids of Tax-1 and two CIITA adjacent regions (amino acids 1 to 252 and 253 to 410). Interestingly, only CIITA 1-252 mediated Tax-1 inhibition, in agreement with the fact that CIITA residues from positions 64 to 124 were required to block Tax-1 transactivation. CIITA inhibitory action on Tax-1 correlated with the nuclear localization of CIITA and was independent of the transcription factor NF-YB, previously involved in CIITA-mediated inhibition of Tax-2 of HTLV-2. Instead, CIITA severely impaired the physical and functional interaction of Tax-1 with the cellular coactivators p300/CBP-associated factor (PCAF), cyclic AMP-responsive element binding protein (CREB), and activating transcription factor 1 (ATF1), which are required for the optimal activation of HTLV-1 promoter. Accordingly, the overexpression of PCAF, CREB, and ATF1 restored Tax-1-dependent transactivation of the viral long-terminal-repeat promoter inhibited by CIITA. These findings strongly support our original observation that CIITA, beside increasing the antigen-presenting function for pathogen antigens, acts as an endogenous restriction factor against human retroviruses by blocking virus replication and spreading.

  12. Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study

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    Rybicki Ed

    2009-08-01

    Full Text Available Abstract Background Cervical cancer and infection with human immunodeficiency virus (HIV are both important public health problems in South Africa (SA. The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs, high-risk human papillomavirus (HR-HPV, HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV therapy. Methods A cross-sectional survey was conducted at an anti-retroviral (ARV treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2 test was used to detect HR-HPV. Relative light units (RLU were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. Results The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene, the median HPV viral load was 181.1 RLU (HC2 positive samples only and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL. The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7 for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load, and 33.8 (95% CI 6.4 – 178.9 for those that were HC2 positive with a HPV viral load > 181.1 RLU. Conclusion Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need

  13. Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance

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    Pignattari Elena

    2001-09-01

    Full Text Available Abstract Background Many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively. Objectives To evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis. Methods The clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed. Results Hyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%. Hyperamylasemia was more likely (17% where a microorganism could be identified in the stools (p Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 % and 10/45 (22.2%, respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P Conclusions Hyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.

  14. [Gastroenteritis-related seizures: study of incidence and clinical analysis].

    Science.gov (United States)

    Lacasa Maseri, S; Ramos Fernández, J M; Moreno Pérez, D; Urda Cardona, A; Martínez Antón, J

    2013-09-01

    Benign convulsions associated with gastroenteritis are now increasingly recognized as clinical condition to the extent that it has become an independent entity under the heading of non-epileptic situational seizures. The aim of this study is to determine the annual incidence in the reference population of our hospital and the clinical characterization of seizures associated to gastroenteritis, in the absence or presence of fever for comparison. All seizures associated with gastroenteritis treated in our hospital were prospectively collected over a period of two calendar years. The children included were aged 6 months to 6 years with seizures in the context of gastroenteritis without electrolyte abnormalities, and divided into two groups, with and without fever. There were 14 cases from a reference population of 39,900 with a homogeneous semiological presentation. The annual incidence was estimated at 1/10 000 children for afebrile seizures associated with gastroenteritis. The clinical behaviour and the incidence of seizures associated with fever and gastroenteritis was similar, but with an appearance somewhat earlier from the onset of symptoms, and at a slightly higher age. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  15. Global Economic Burden of Norovirus Gastroenteritis

    Science.gov (United States)

    Bartsch, Sarah M.; Lopman, Benjamin A.; Ozawa, Sachiko; Hall, Aron J.; Lee, Bruce Y.

    2016-01-01

    Background Despite accounting for approximately one fifth of all acute gastroenteritis illnesses, norovirus has received comparatively less attention than other infectious pathogens. With several candidate vaccines under development, characterizing the global economic burden of norovirus could help funders, policy makers, public health officials, and product developers determine how much attention and resources to allocate to advancing these technologies to prevent and control norovirus. Methods We developed a computational simulation model to estimate the economic burden of norovirus in every country/area (233 total) stratified by WHO region and globally, from the health system and societal perspectives. We considered direct costs of illness (e.g., clinic visits and hospitalization) and productivity losses. Results Globally, norovirus resulted in a total of $4.2 billion (95% UI: $3.2–5.7 billion) in direct health system costs and $60.3 billion (95% UI: $44.4–83.4 billion) in societal costs per year. Disease amongst children norovirus illness varied by both region and age and was highest among adults ≥55 years. Productivity losses represented 84–99% of total costs varying by region. While low and middle income countries and high income countries had similar disease incidence (10,148 vs. 9,935 illness per 100,000 persons), high income countries generated 62% of global health system costs. In sensitivity analysis, the probability of hospitalization had the largest impact on health system cost estimates ($2.8 billion globally, assuming no hospitalization costs), while the probability of missing productive days had the largest impact on societal cost estimates ($35.9 billion globally, with a 25% probability of missing productive days). Conclusions The total economic burden is greatest in young children but the highest cost per illness is among older age groups in some regions. These large costs overwhelmingly are from productivity losses resulting from acute

  16. Global Economic Burden of Norovirus Gastroenteritis.

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    Sarah M Bartsch

    Full Text Available Despite accounting for approximately one fifth of all acute gastroenteritis illnesses, norovirus has received comparatively less attention than other infectious pathogens. With several candidate vaccines under development, characterizing the global economic burden of norovirus could help funders, policy makers, public health officials, and product developers determine how much attention and resources to allocate to advancing these technologies to prevent and control norovirus.We developed a computational simulation model to estimate the economic burden of norovirus in every country/area (233 total stratified by WHO region and globally, from the health system and societal perspectives. We considered direct costs of illness (e.g., clinic visits and hospitalization and productivity losses.Globally, norovirus resulted in a total of $4.2 billion (95% UI: $3.2-5.7 billion in direct health system costs and $60.3 billion (95% UI: $44.4-83.4 billion in societal costs per year. Disease amongst children <5 years cost society $39.8 billion, compared to $20.4 billion for all other age groups combined. Costs per norovirus illness varied by both region and age and was highest among adults ≥55 years. Productivity losses represented 84-99% of total costs varying by region. While low and middle income countries and high income countries had similar disease incidence (10,148 vs. 9,935 illness per 100,000 persons, high income countries generated 62% of global health system costs. In sensitivity analysis, the probability of hospitalization had the largest impact on health system cost estimates ($2.8 billion globally, assuming no hospitalization costs, while the probability of missing productive days had the largest impact on societal cost estimates ($35.9 billion globally, with a 25% probability of missing productive days.The total economic burden is greatest in young children but the highest cost per illness is among older age groups in some regions. These large

  17. Norovirus genotype diversity associated with gastroenteritis outbreaks in aged-care facilities.

    Science.gov (United States)

    Bruggink, L D; Dunbar, N L; Marshall, J A

    2015-10-01

    Noroviruses are a major cause of gastroenteritis. Vaccine strategies against norovirus are currently under consideration but depend on a detailed knowledge of the capsid genotypes. This study examined the incidence of norovirus outbreaks in residential aged-care facilities in Victoria, Australia over one year (2013) and documented the (capsid) norovirus genotypes associated with these outbreaks. It was found that 65·0% of 206 outbreaks tested were associated with norovirus infection, thereby showing norovirus to be the major cause of viral gastroenteritis in residential aged-care facilities. Fifteen capsid (open reading frame 2) genotypes were identified as follows: GI.2 (0·9%), GI.3 (1·8%), GI.4 (3·7%), GI.6 (0·9%), GI.7 (0·9%), GI.8 (0·9%), GII.1 (0·9%), GII.2 (0·9%), GII.3 (1·8%), GII.4 (2009-like) (0·9%), GII.4 (2012) (48·6%), GII.4 (2012-like) (16·5%), GII.4 (unknown) (9·2%), GII.5 (2·8%), GII.6 (0·9%), GII.7 (0·9%), GII.13 (6·4%) and an as yet unclassified GII genotype (0·9%). Although GII.4 was the most common norovirus capsid genotype detected, the great diversity of norovirus genotypes in the elderly indicates vaccination strategies for this demographic are not straightforward.

  18. Outbreak of acute gastroenteritis caused by contamination of drinking water in a factory, the Basque Country.

    Science.gov (United States)

    Altzibar, J M; Zigorraga, C; Rodriguez, R; Leturia, N; Garmendia, A; Rodriguez, A; Alkorta, M; Arriola, L

    2015-03-01

    On 18 September 2013, the Gipuzkoa Epidemiology Unit was notified of an outbreak of acute gastroenteritis (AGE) among employees at a domestic appliance factory. The first signs of the outbreak had emerged at the end of June and at the time of the notification 30 workers were on sick leave for gastroenteritis. Some employees had had more than one episode and the main symptoms were diarrhoea and vomiting. An investigation began to identify the causative agent, assess exposure and determine the route of transmission. Data collected by a questionnaire identified 302 episodes of AGE among 238 people affected between June and September 2013. The source of water consumed was found to be a risk factor associated with the appearance of symptoms both in the crude and the adjusted analysis: odds ratio 1.8 (0.8-4.2) and 6.4 (4.2-9.8), respectively. Microbiological analysis of stool samples and of water confirmed the presence of norovirus and rotavirus. The environmental study detected a connection between an industrial use water system and drinking water at the factory. It was concluded that the outbreak was caused by mixed viral infections, due to contamination of drinking water.

  19. Approaches to immunization of infants and young children against gastroenteritis due to rotaviruses.

    Science.gov (United States)

    Kapikian, A Z; Wyatt, R G; Greenberg, H B; Kalica, A R; Kim, H W; Brandt, C D; Rodriguez, W J; Parrott, R H; Chanock, R M

    1980-01-01

    Recent studies have shown that in developed countries rotaviruses are the single most important etiologic agents of acute gastroenteritis that requires hospitalization of infants and young children. Although deaths from gastroenteritis are, in general, infrequent in the developed countries, an effective rotavirus vaccine would clearly be of benefit to reduce the heavy toll of morbidity from gastroenteritis due to rotavirus. In the developing countries the impact of diarrheal diseases is staggering. It was recently estimated that in Asia, Africa, and Latin-America during a one-year period there would be 3.5 billion cases of diarrhea and 5-10 million deaths associated with diarrhea; in addition, diarrhea was ranked first in freqency in the categories of disease and mortality. In the developing countries rotaviruses are known to cause diarrhea, but their relative role in this high mortality rate is not yet known. epidemiologic data indicate that development of an effective rotavirus vaccine would reduce morbidity, and they suggest that a vaccine would also reduce a portion of the mortality from diarrheal disease. The prospects and approaches for the development of an effective rotavirus vaccine are presented. The recent successful propagation of rotavirus type 2 in cell culture represents an important step in this regard. In addition, the antigenic relation between human and animal strains offers another possible approach. The need for a live attenuated vaccine is indicated by the prime role played by local intestinal immunity in resistance to rotavirus disease.

  20. The Nuclear DNA Sensor IFI16 Acts as a Restriction Factor for Human Papillomavirus Replication through Epigenetic Modifications of the Viral Promoters.

    Science.gov (United States)

    Lo Cigno, Irene; De Andrea, Marco; Borgogna, Cinzia; Albertini, Silvia; Landini, Manuela M; Peretti, Alberto; Johnson, Karen E; Chandran, Bala; Landolfo, Santo; Gariglio, Marisa

    2015-08-01

    The human interferon-inducible IFI16 protein, an innate immune sensor of intracellular DNA, was recently demonstrated to act as a restriction factor for human cytomegalovirus (HCMV) and herpes simplex virus 1 (HSV-1) infection by inhibiting both viral-DNA replication and transcription. Through the use of two distinct cellular models, this study provides strong evidence in support of the notion that IFI16 can also restrict human papillomavirus 18 (HPV18) replication. In the first model, an immortalized keratinocyte cell line (NIKS) was used, in which the IFI16 protein was knocked down through the use of small interfering RNA (siRNA) technology and overexpressed following transduction with the adenovirus IFI16 (AdVIFI16) vector. The second model consisted of U2OS cells transfected by electroporation with HPV18 minicircles. In differentiated IFI16-silenced NIKS-HPV18 cells, viral-load values were significantly increased compared with differentiated control cells. Consistent with this, IFI16 overexpression severely impaired HPV18 replication in both NIKS and U2OS cells, thus confirming its antiviral restriction activity. In addition to the inhibition of viral replication, IFI16 was also able to reduce viral transcription, as demonstrated by viral-gene expression analysis in U2OS cells carrying episomal HPV18 minicircles and HeLa cells. We also provide evidence that IFI16 promotes the addition of heterochromatin marks and the reduction of euchromatin marks on viral chromatin at both early and late promoters, thus reducing both viral replication and transcription. Altogether, these results argue that IFI16 restricts chromatinized HPV DNA through epigenetic modifications and plays a broad surveillance role against viral DNA in the nucleus that is not restricted to herpesviruses. Intrinsic immunity is mediated by cellular restriction factors that are constitutively expressed and active even before a pathogen enters the cell. The host nuclear factor IFI16 acts as a sensor

  1. Gastroenteric tube feeding: Techniques, problems and solutions

    Science.gov (United States)

    Blumenstein, Irina; Shastri, Yogesh M; Stein, Jürgen

    2014-01-01

    Gastroenteric tube feeding plays a major role in the management of patients with poor voluntary intake, chronic neurological or mechanical dysphagia or gut dysfunction, and patients who are critically ill. However, despite the benefits and widespread use of enteral tube feeding, some patients experience complications. This review aims to discuss and compare current knowledge regarding the clinical application of enteral tube feeding, together with associated complications and special aspects. We conducted an extensive literature search on PubMed, Embase and Medline using index terms relating to enteral access, enteral feeding/nutrition, tube feeding, percutaneous endoscopic gastrostomy/jejunostomy, endoscopic nasoenteric tube, nasogastric tube, and refeeding syndrome. The literature showed common routes of enteral access to include nasoenteral tube, gastrostomy and jejunostomy, while complications fall into four major categories: mechanical, e.g., tube blockage or removal; gastrointestinal, e.g., diarrhea; infectious e.g., aspiration pneumonia, tube site infection; and metabolic, e.g., refeeding syndrome, hyperglycemia. Although the type and frequency of complications arising from tube feeding vary considerably according to the chosen access route, gastrointestinal complications are without doubt the most common. Complications associated with enteral tube feeding can be reduced by careful observance of guidelines, including those related to food composition, administration rate, portion size, food temperature and patient supervision. PMID:25024606

  2. Cell-cycle-dependent localization of human cytomegalovirus UL83 phosphoprotein in the nucleolus and modulation of viral gene expression in human embryo fibroblasts in vitro.

    Science.gov (United States)

    Arcangeletti, Maria-Cristina; Rodighiero, Isabella; Mirandola, Prisco; De Conto, Flora; Covan, Silvia; Germini, Diego; Razin, Sergey; Dettori, Giuseppe; Chezzi, Carlo

    2011-01-01

    The nucleolus is a multifunctional nuclear compartment widely known to be involved in several cellular processes, including mRNA maturation and shuttling to cytoplasmic sites, control of the cell cycle, cell proliferation, and apoptosis; thus, it is logical that many viruses, including herpesvirus, target the nucleolus in order to exploit at least one of the above-mentioned functions. Recent studies from our group demonstrated the early accumulation of the incoming ppUL83 (pp65), the major tegument protein of human cytomegalovirus (HCMV), in the nucleolus. The obtained results also suggested that a functional relationship might exist between the nucleolar localization of pp65, rRNA synthesis, and the development of the lytic program of viral gene expression. Here we present new data which support the hypothesis of a potentially relevant role of HCMV pp65 and its nucleolar localization for the control of the cell cycle by HCMV (arrest of cell proliferation in G1-G1/S), and for the promotion of viral infection. We demonstrated that, although the incoming pp65 amount in the infected cells appears to be constant irrespective of the cell-cycle phase, its nucleolar accumulation is prominent in G1 and G1/S, but very poor in S or G2/M. This correlates with the observation that only cells in G1 and G1/S support an efficient development of the HCMV lytic cycle. We propose that HCMV pp65 might be involved in regulatory/signaling pathways related to nucleolar functions, such as the cell-cycle control. Co-immunoprecipitation experiments have permitted to identify nucleolin as one of the nucleolar partners of pp65.

  3. Viral pathogens including human metapneumovirus are the primary cause of febrile respiratory illness in HIV-infected adults receiving antiretroviral therapy.

    Science.gov (United States)

    Klein, Marina B; Yang, Hong; DelBalso, Lina; Carbonneau, Julie; Frost, Eric; Boivin, Guy

    2010-01-15

    To determine the spectrum of pathogens causing acute febrile respiratory illness in human immunodeficiency virus (HIV)-infected adults, we re-analyzed data from a prospective surveillance study involving 50 outpatients (90% of whom received highly active antiretroviral therapy). Nasopharyngeal samples were tested for 23 respiratory viruses by multiplex reverse-transcriptase polymerase chain reaction (PCR) and for atypical bacteria by PCR. Sputum cultures and serological testing were performed. Viruses accounted for 64% of infections. After influenza (22 cases), human metapneumovirus infection (6 cases) was most common and was associated with bronchospasm. Bacterial infections occurred in 6 patients (3 of whom had concurrent viral infection). Over 80% of patients received antibiotics. Rapid testing to identify specific viral pathogens could aid in patient management and reduce unnecessary antibiotic exposure.

  4. [Hospitalisation associated with Rotavirus gastroenteritis in Italy, 2001-2003, evaluated by means of ICD9-CM diagnostic codes].

    Science.gov (United States)

    Marocco, Alessia; Assael, Baroukh; Gabutti, Giovanni; Guarino, Alfredo; Lopalco, Pier Luigi; Marchetti, Federico; Ruggeri, Franco Maria; Titone, Lucina; Tozzi, Alberto Eugenio; Vitali Rosati, Giovanni; Zotti, Carla; Franco, Elisabetta

    2006-01-01

    Rotaviruses (RV) are the most common etiological agents in acute gastroenteritis (GE) in children in the first years of life. Data from the national scientific literature show that RV is responsible of 26% of all cases of hospitalisation for diarrea in children, resulting the most frequently identified agent. The Italian database of hospital discharge, freely available from the web site of the national Ministry of Health, was searched to investigate the epidemiology of RV gastroenteritis. The mean number of hospitalisation for RV enteritis in children in the first 4 years of live was 4.758 in the years 2001, 2002 and 2003, representing 84% of viral enteritis. RV was identified as agent in 17% of all intestinal infectious diseases in this age group. This percentage shows the important role of RV in severe gastrointestinal infections; it is however much lower than the value expected from specifically performed surveys. This underestimation may be attributed to the high number of undefined gastroenteritis found in the database (54%), to the scarce sensitivity of the hospital discharge code, and to the fact that the analysis was performed using only the principal diagnosis. A specific immunisation strategy, safe, effective, cost-effective and easy to perform, could have a great impact on the incidence of the disease and on the associated costs.

  5. Quality Control Assessment of Human Immunodeficiency Virus Type 2 (HIV-2) Viral Load Quantification Assays: Results from an International Collaboration on HIV-2 Infection in 2006▿

    Science.gov (United States)

    Damond, Florence; Benard, Antoine; Ruelle, Jean; Alabi, Abraham; Kupfer, Bernd; Gomes, Perpetua; Rodes, Berta; Albert, Jan; Böni, Jürg; Garson, Jeremy; Ferns, Bridget; Matheron, Sophie; Chene, Geneviève; Brun-Vezinet, Françoise

    2008-01-01

    Human immunodeficiency virus type 2 (HIV-2) RNA quantification assays used in nine laboratories of the ACHIEV2E (A Collaboration on HIV-2 Infection) study group were evaluated. In a blinded experimental design, laboratories quantified three series of aliquots of an HIV-2 subtype A strain, each at a different theoretical viral load. Quantification varied between laboratories, and international standardization of quantification assays is strongly needed. PMID:18434556

  6. Socio-demographic, Clinical and Laboratory Features of Rotavirus Gastroenteritis in Children Treated in Pediatric Clinic

    Science.gov (United States)

    Azemi, Mehmedali; Berisha, Majlinda; Ismaili-Jaha, Vlora; Kolgeci, Selim; Avdiu, Muharrem; Jakupi, Xhevat; Hoxha, Rina; Hoxha-Kamberi, Teuta

    2013-01-01

    Aim: The aim of work was presentation of several socio-demographic, clinical and laboratory characteristics of gastroenteritis caused by rotavirus. The examinees and methods: The examinees were children under the age of five years treated at the Pediatric Clinic due to acute gastroenteritis caused by rotavirus. Rotavirus is isolated by method chromatographic immunoassay by Cer Test Biotec. Results: From the total number of patients (850) suffering from acute gastroenteritis, feces test on bacteria, viruses. protozoa and fungi was positive in 425 (49.76%) cases. From this number the test on bacteria was positive in 248 (58.62%) cases, on viruses it was positive in 165 (39.0%), on protozoa in 9 (2.12%) cases and on fungi only one case. Rotavirus was the most frequent one in viral test, it was isolated in 142 (86.06%) cases, adenoviruses were found in 9 (5.45%) cases and noroviruses in only one case. The same feces sample that contained rotavirus and adenoviruses were isolated in five cases, whereas rotavirus with bacteria was isolated in the same feces sample in five cases. The biggest number of cases 62 (43.66%) were of the age 6-12 months, whereas the smallest number 10 (7.04%) cases were of the age 37-60 months. There were 76 (53.52%) of cases of male gender, from rural areas there were 81 (57.04%) cases and there were 58 (40.80%) cases during the summer period. Among the clinical symptoms the most prominent were diarrhea, vomiting, high temperature, whereas the different degree of dehydration were present in all cases (the most common one was moderate dehydration). The most frequent one was isonatremic dehydration in 91 (64.08%) cases, less frequent one was hypernatremic dehydration in 14 (9.85%) cases. The majority of cases (97.89%) had lower blood pH values, whereas 67 (47.17%) cases had pH values that varied from 7.16 -7.20 (curve peak), normal values were registered in only 3 (2.11%) cases. Urea values were increased in 45 (31.07%) cases (the maximum value

  7. Hybrid adeno-associated viral vectors utilizing transposase-mediated somatic integration for stable transgene expression in human cells.

    Directory of Open Access Journals (Sweden)

    Wenli Zhang

    Full Text Available Recombinant adeno-associated viral (AAV vectors have been shown to be one of the most promising vectors for therapeutic gene delivery because they can induce efficient and long-term transduction in non-dividing cells with negligible side-effects. However, as AAV vectors mostly remain episomal, vector genomes and transgene expression are lost in dividing cells. Therefore, to stably transduce cells, we developed a novel AAV/transposase hybrid-vector. To facilitate SB-mediated transposition from the rAAV genome, we established a system in which one AAV vector contains the transposon with the gene of interest and the second vector delivers the hyperactive Sleeping Beauty (SB transposase SB100X. Human cells were infected with the AAV-transposon vector and the transposase was provided in trans either by transient and stable plasmid transfection or by AAV vector transduction. We found that groups which received the hyperactive transposase SB100X showed significantly increased colony forming numbers indicating enhanced integration efficiencies. Furthermore, we found that transgene copy numbers in transduced cells were dose-dependent and that predominantly SB transposase-mediated transposition contributed to stabilization of the transgene. Based on a plasmid rescue strategy and a linear-amplification mediated PCR (LAM-PCR protocol we analysed the SB100X-mediated integration profile after transposition from the AAV vector. A total of 1840 integration events were identified which revealed a close to random integration profile. In summary, we show for the first time that AAV vectors can serve as template for SB transposase mediated somatic integration. We developed the first prototype of this hybrid-vector system which with further improvements may be explored for treatment of diseases which originate from rapidly dividing cells.

  8. Development of a fluorescence-based multiplex genotyping method for simultaneous determination of human papillomavirus infections and viral loads.

    Science.gov (United States)

    Sun, Zhengrong; Zhang, Rong; Liu, Zhonghua; Liu, Chao; Li, Xiulin; Zhou, Weiqiang; Yang, Lianxia; Ruan, Qiang; Zhang, Xu

    2015-11-06

    Persistent high-risk human papillomavirus (HPV) infection is correlated with an increased risk of developing intraepithelial lesion or malignancy (NILM). The aims of the current study is to establish a method named BioPerfectus Multiplex Real Time (BMRT) HPV assay for simultaneous typing and quantifying HPVs, and to evaluate it by comparison with HPV GenoArray test and PCR-sequencing method, as well as histological status. A total of 817 cervical specimens were evaluated by BMRT method and HPV GenoArray test, using PCR-sequencing method as the reference standard; simultaneously, high-risk HPV-16 and -18 DNA loads were assessed in 443 specimens to investigate the correlation with infection outcomes. The overall detection coincidence rate between BMRT assay and HPV GenoArray test is 96.6 % and the Kappa value is 0.760. In addition, the sensitivity and positive predictive value of BMRT is 98.4 % and 95.7 % compared with the results detected by PCR-sequencing method, respectively. HPV-16 viral load has a correlation with CINs or worse lesions. By comparing with infected women presenting NILM /cervicitis, the cutoff value for HPV-16 from patients with CINs was 0.827. With this cutoff value, 74.6 % sensitivity and 72.5 % specificity for prediction of HPV-16 infected patients with CINI and higher CIN were achieved. High significance was obtained when comparing the infected women presenting NILM/cervicitis with women either with CIN and cervical carcinomas (p HPV testing, due to its high level of automation and ability to quantify HPV-16, HPV-18 and other HR-HPVs.

  9. Characterization of Adeno-Associated Viral Vector-Mediated Human Factor VIII Gene Therapy in Hemophilia A Mice.

    Science.gov (United States)

    Greig, Jenny A; Wang, Qiang; Reicherter, Amanda L; Chen, Shu-Jen; Hanlon, Alexandra L; Tipper, Christopher H; Clark, K Reed; Wadsworth, Samuel; Wang, Lili; Wilson, James M

    2017-05-01

    Adeno-associated viral (AAV) vectors are promising vehicles for hemophilia gene therapy, with favorable clinical trial data seen in the treatment of hemophilia B. In an effort to optimize the expression of human coagulation factor VIII (hFVIII) for the treatment of hemophilia A, an extensive study was performed with numerous combinations of liver-specific promoter and enhancer elements with a codon-optimized hFVIII transgene. After generating 42 variants of three reduced-size promoters and three small enhancers, transgene cassettes were packaged within a single AAV capsid, AAVrh10, to eliminate performance differences due to the capsid type. Each hFVIII vector was administered to FVIII knockout (KO) mice at a dose of 10(10) genome copies (GC) per mouse. Criteria for distinguishing the performance of the different enhancer/promoter combinations were established prior to the initiation of the studies. These criteria included prominently the level of hFVIII activity (0.12-2.12 IU/mL) and the pattern of development of anti-hFVIII antibodies. In order to evaluate the impact of capsid on hFVIII expression and antibody formation, one of the enhancer and promoter combinations that exhibited high hFVIII immunogenicity was evaluated using AAV8, AAV9, AAVrh10, AAVhu37, and AAVrh64R1 capsids. The capsids subdivided into two groups: those that generated anti-hFVIII antibodies in ≤20% of mice (AAV8 and AAV9), and those that generated anti-hFVIII antibodies in >20% of mice (AAVrh10, AAVhu37, and AAVrh64R1). The results of this study, which entailed extensive vector optimization and in vivo testing, demonstrate the significant impact that transcriptional control elements and capsid can have on vector performance.

  10. Mycobacterial and HIV infections up-regulated human zinc finger protein 134, a novel positive regulator of HIV-1 LTR activity and viral propagation.

    Directory of Open Access Journals (Sweden)

    Ronald Benjamin

    Full Text Available BACKGROUND: Concurrent occurrence of HIV and Tuberculosis (TB infections influence the cellular environment of the host for synergistic existence. An elementary approach to understand such coalition at the molecular level is to understand the interactions of the host and the viral factors that subsequently effect viral replication. Long terminal repeats (LTR of HIV genome serve as a template for binding trans-acting viral and cellular factors that regulate its transcriptional activity, thereby, deciding the fate of HIV pathogenesis, making it an ideal system to explore the interplay between HIV and the host. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using biotinylated full length HIV-1 LTR sequence as bait followed by MALDI analyses, we identified and further characterized human-Zinc-finger-protein-134 (hZNF-134 as a novel positive regulator of HIV-1 that promoted LTR-driven transcription and viral production. Over-expression of hZNF-134 promoted LTR driven luciferase activity and viral transcripts, resulting in increased virus production while siRNA mediated knockdown reduced both the viral transcripts and the viral titers, establishing hZNF-134 as a positive effector of HIV-1. HIV, Mycobacteria and HIV-TB co-infections increased hZNF-134 expressions in PBMCs, the impact being highest by mycobacteria. Corroborating these observations, primary TB patients (n = 22 recorded extraordinarily high transcript levels of hZNF-134 as compared to healthy controls (n = 16. CONCLUSIONS/SIGNIFICANCE: With these observations, it was concluded that hZNF-134, which promoted HIV-1 LTR activity acted as a positive regulator of HIV propagation in human host. High titers of hZNF-134 transcripts in TB patients suggest that up-regulation of such positive effectors of HIV-1 upon mycobacterial infection can be yet another mechanism by which mycobacteria assists HIV-1 propagation during HIV-TB co-infections. hZNF-134, an uncharacterized host protein, thus

  11. Enhanced Non-Viral Gene Delivery to Human Embryonic Stem Cells via Small Molecule-Mediated Transient Alteration of Cell Structure.

    Science.gov (United States)

    Yen, Jonathan; Yin, Lichen; Cheng, Jianjun

    Non-viral gene delivery into human embryonic stem cells (hESCs)is an important tool for controlling cell fate. However, the delivery efficiency remains low due in part to the tight colony structure of the cells which prevents effective exposure towards delivery vectors. We herein report a novel approach to enhance non-viral gene delivery to hESCs by transiently altering the cell and colony structure. (R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632), a small molecule that inhibits the rho-associated protein kinase pathway, is utilized to induce transient colony spreading which leads to increased transfection efficiency by 1.5 to 2 folds in a spectrum of non-viral transfection reagents including Lipofectamine 2000 and Fugene HD. After removal of Y-27632 post-transfection, cells can revert back to its normal state and do not show alteration of pluripotency. This approach provides a simple, effective tool to enhance non-viral gene delivery into adherent hESCs for genetic manipulation.

  12. Autologous neutralizing humoral immunity and evolution of the viral envelope in the course of subtype B human immunodeficiency virus type 1 infection.

    Science.gov (United States)

    Bunnik, Evelien M; Pisas, Linaida; van Nuenen, Ad C; Schuitemaker, Hanneke

    2008-08-01

    Most human immunodeficiency virus type 1 (HIV-1)-infected individuals develop an HIV-specific neutralizing antibody (NAb) response that selects for escape variants of the virus. Here, we studied autologous NAb responses in five typical CCR5-using progressors in relation to viral NAb escape and molecular changes in the viral envelope (Env) in the period from seroconversion until after AIDS diagnosis. In sera from three patients, high-titer neutralizing activity was observed against the earliest autologous virus variants, followed by declining humoral immune responses against subsequent viral escape variants. Autologous neutralizing activity was undetectable in sera from two patients. Patients with high-titer neutralizing activity in serum showed the strongest positive selection pressure on Env early in infection. In the initial phase of infection, gp160 length and the number of potential N-linked glycosylation sites (PNGS) increased in viruses from all patients. Over the course of infection, positive selection pressure declined as the NAb response subsided, coinciding with reversions of changes in gp160 length and the number of PNGS. A number of identical amino acid changes were observed over the course of infection in the viral quasispecies of different patients. Our results indicate that although neutralizing autologous humoral immunity may have a limited effect on the disease course, it is an important selection pressure in virus evolution early in infection, while declining HIV-specific humoral immunity in later stages may coincide with reversion of NAb-driven changes in Env.

  13. Association of human mitochondrial lysyl-tRNA synthetase with HIV-1 GagPol does not require other viral proteins

    Directory of Open Access Journals (Sweden)

    Lydia Kobbi

    2016-06-01

    Full Text Available In human, the cytoplasmic (cLysRS and mitochondrial (mLysRS species of lysyl-tRNA synthetase are encoded by a single gene. Following HIV-1 infection, mLysRS is selectively taken up into viral particles along with the three tRNALys isoacceptors. The GagPol polyprotein precursor is involved in this process. With the aim to reconstitute in vitro the HIV-1 tRNA3Lys packaging complex, we first searched for the putative involvement of another viral protein in the selective viral hijacking of mLysRS only. After screening all the viral proteins, we observed that Vpr and Rev have the potential to interact with mLysRS, but that this association does not take place at the level of the assembly of mLysRS into the packaging complex. We also show that tRNA3Lys can form a ternary complex with the two purified proteins mLysRS and the Pol domain of GagPol, which mimicks its packaging complex.

  14. [Pathology and viral metagenomics, a recent history].

    Science.gov (United States)

    Bernardo, Pauline; Albina, Emmanuel; Eloit, Marc; Roumagnac, Philippe

    2013-05-01

    Human, animal and plant viral diseases have greatly benefited from recent metagenomics developments. Viral metagenomics is a culture-independent approach used to investigate the complete viral genetic populations of a sample. During the last decade, metagenomics concepts and techniques that were first used by ecologists progressively spread into the scientific field of viral pathology. The sample, which was first for ecologists a fraction of ecosystem, became for pathologists an organism that hosts millions of microbes and viruses. This new approach, providing without a priori high resolution qualitative and quantitative data on the viral diversity, is now revolutionizing the way pathologists decipher viral diseases. This review describes the very last improvements of the high throughput next generation sequencing methods and discusses the applications of viral metagenomics in viral pathology, including discovery of novel viruses, viral surveillance and diagnostic, large-scale molecular epidemiology, and viral evolution. © 2013 médecine/sciences – Inserm.

  15. A Tool for Investigating Asthma and COPD Exacerbations: A Newly Manufactured and Well Characterised GMP Wild-Type Human Rhinovirus for Use in the Human Viral Challenge Model.

    Directory of Open Access Journals (Sweden)

    Daniel J Fullen

    Full Text Available Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose.A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children's Hospital, USA was obtained with appropriate medical history and consent. We manufactured a new HRV-16 stock by minimal passage in a WI-38 cell line under Good Manufacturing Practice conditions. Having first subjected the stock to rigorous adventitious agent testing and determining the virus suitability for human use, we conducted an initial safety and pathogenicity clinical study in adult volunteers in our dedicated clinical quarantine facility in London.In this study we have demonstrated the new Wild-Type HRV-16 Challenge Virus to be both safe and pathogenic, causing an appropriate level of disease in experimentally inoculated healthy adult volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we have established the minimum inoculum titre required to achieve reproducible disease. We have demonstrated that although inoculation titres as low as 1 TCID50 can produce relatively high infection rates, the optimal titre for progression with future HRV challenge model development with this virus stock was 10 TCID50. Studies currently underway are evaluating the use of this virus as a challenge agent in asthmatics.ClinicalTrials.gov NCT02522832.

  16. Antiviral effects of black raspberry (Rubus coreanus) juice on foodborne viral surrogates.

    Science.gov (United States)

    Oh, Mi; Bae, Seon Young; Lee, Ji-Hye; Cho, Ki Joon; Kim, Kyung Hyun; Chung, Mi Sook

    2012-10-01

    Abstract Human noroviruses (HuNoVs) are the most frequent cause of foodborne viral gastroenteritis, causing approximately 90% of non-bacterial epidemic outbreaks around the world. Rubus coreanus is a species of black raspberry, rich in polyphenols, and known to exert anti-inflammatory, antibacterial, and antiviral activities. In the present study, the antiviral effects of R. coreanus juice (black raspberry [BRB] juice) on foodborne viral surrogates, murine norovirus-1 (MNV-1) and feline calicivirus-F9 (FCV-F9), were compared with those of cranberry juice, grape juice, and orange juice by plaque assays. Among the four juices tested, BRB juice was the most effective in reducing plaques formation of these viruses. Time-of-addition experiments were designed to determine the mechanism of action of BRB juice on MNV-1 and FCV-F9. The maximal antiviral effect of BRB juice against MNV-1 was observed when it was added to RAW 264.7 cells (mouse leukemic monocyte macrophage cell line) simultaneously with the virus. Pre-treatment of either Crandell Reese Feline Kidney cells or FCV-F9 with BRB juice exhibited significant antiviral activity. The inhibition of viral infection by BRB juice on MNV-1 and FCV-F9 probably occurs at the internalization of virions into the cell or the attachment of the viral surface protein to the cellular receptor. The polyphenol components in BRB (i.e., gallic acid and quercetin), however, did not show any activity against these viruses. Our data provide great promise for the utilization of BRB in the prevention of foodborne viral outbreaks.

  17. Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages.

    Science.gov (United States)

    Machkovech, Heather M; Bedford, Trevor; Suchard, Marc A; Bloom, Jesse D

    2015-11-01

    Numerous experimental studies have demonstrated that CD8(+) T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8(+) T cells. Here we use a novel computational approach to test for selection in CD8(+) T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8(+) T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8(+) T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8(+) T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint. There is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8(+) T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal

  18. Complete genome sequence of an astrovirus identified in a domestic rabbit (Oryctolagus cuniculus with gastroenteritis

    Directory of Open Access Journals (Sweden)

    Stenglein Mark D

    2012-09-01

    Full Text Available Abstract A colony of domestic rabbits in Tennessee, USA, experienced a high-mortality (~90% outbreak of enterocolitis. The clinical characteristics were one to six days of lethargy, bloating, and diarrhea, followed by death. Heavy intestinal coccidial load was a consistent finding as was mucoid enteropathy with cecal impaction. Preliminary analysis by electron microscopy revealed the presence of virus-like particles in the stool of one of the affected rabbits. Analysis using the Virochip, a viral detection microarray, suggested the presence of an astrovirus, and follow-up PCR and sequence determination revealed a previously uncharacterized member of that family. Metagenomic sequencing enabled the recovery of the complete viral genome, which contains the characteristic attributes of astrovirus genomes. Attempts to propagate the virus in tissue culture have yet to succeed. Although astroviruses cause gastroenteric disease in other mammals, the pathogenicity of this virus and the relationship to this outbreak remains to be determined. This study therefore defines a viral species and a potential rabbit pathogen.

  19. The influence of the human genome on chronic viral hepatitis outcome A influência do genoma humano no curso das hepatites virais crônicas

    Directory of Open Access Journals (Sweden)

    Dahir Ramos de Andrade Júnior

    2004-06-01

    Full Text Available The mechanisms that determine viral clearance or viral persistence in chronic viral hepatitis have yet to be identified. Recent advances in molecular genetics have permitted the detection of variations in immune response, often associated with polymorphism in the human genome. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virulence of microbial agents. Several recent advances concerning the influence of human genes in chronic viral hepatitis B and C are discussed in this article: a the associations between human leukocyte antigen polymorphism and viral hepatic disease susceptibility or resistance; b protective alleles influencing hepatitis B virus (HBV and hepatitis C virus (HCV evolution; c prejudicial alleles influencing HBV and HCV; d candidate genes associated with HBV and HCV evolution; d other genetic factors that may contribute to chronic hepatitis C evolution (genes influencing hepatic stellate cells, TGF-beta1 and TNF-alpha production, hepatic iron deposits and angiotensin II production, among others. Recent discoveries regarding genetic associations with chronic viral hepatitis may provide clues to understanding the development of end-stage complications such as cirrhosis or hepatocellular carcinoma. In the near future, analysis of the human genome will allow the elucidation of both the natural course of viral hepatitis and its response to therapy.Os mecanismos que determinam o clearance ou a persistência da infecção viral nas hepatites virais crônicas não estão ainda bem identificados. O progresso no conhecimento sobre as ferramentas genéticas moleculares tem permitido detectar variações na resposta imune, que freqüentemente são associadas com polimorfismos do genoma humano. As diferenças na susceptibilidade do hospedeiro para as doenças infecciosas e a intensidade das doenças não podem ser atribuídas apenas à virulência do agente microbiano. Neste

  20. Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection.

    LENUS (Irish Health Repository)

    O'Shea, D

    2013-02-26

    Dendritic cells (DCs) are key immune sentinels linking the innate and adaptive immune systems. DCs recognise danger signals and initiate T-cell tolerance, memory and polarisation. They are critical cells in responding to a viral illness. Obese individuals have been shown to have an impaired response to vaccinations against virally mediated conditions and to have an increased susceptibility to multi-organ failure in response to viral illness. We investigated if DCs are altered in an obese cohort (mean body mass index 51.7±7.3 kg m(-2)), ultimately resulting in differential T-cell responses. Circulating DCs were found to be significantly decreased in the obese compared with the lean cohort (0.82% vs 2.53%). Following Toll-like receptor stimulation, compared with lean controls, DCs generated from the obese cohort upregulated significantly less CD83 (40% vs 17% mean fluorescence intensity), a molecule implicated in the elicitation of T-cell responses, particularly viral responses. Obese DCs produced twofold more of the immunosuppressive cytokine interleukin (IL)-10 than lean controls, and in turn stimulated fourfold more IL-4-production from allogenic naive T cells. We conclude that obesity negatively impacts the ability of DCs to mature and elicit appropriate T-cell responses to a general stimulus. This may contribute to the increased susceptibility to viral infection observed in severe obesity.International Journal of Obesity advance online publication, 26 February 2013; doi:10.1038\\/ijo.2013.16.

  1. Valuable Virality

    NARCIS (Netherlands)

    Akpinar, E.; Berger, Jonah

    2017-01-01

    Given recent interest in social media, many brands now create content that they hope consumers will view and share with peers. While some campaigns indeed go “viral,” their value to the brand is limited if they do not boost brand evaluation or increase purchase. Consequently, a key question is how

  2. Association of Human Papillomavirus 16 E2 with Rad50-Interacting Protein 1 Enhances Viral DNA Replication.

    Science.gov (United States)

    Campos-León, Karen; Wijendra, Kalpanee; Siddiqa, Abida; Pentland, Ieisha; Feeney, Katherine M; Knapman, Alison; Davies, Rachel; Androphy, Elliot J; Parish, Joanna L

    2017-03-01

    Rad50-interacting protein 1 (Rint1) associates with the DNA damage response protein Rad50 during the transition from the S phase to the G2/M phase and functions in radiation-induced G2 checkpoint control. It has also been demonstrated that Rint1 is essential in vesicle trafficking from the Golgi apparatus to the endoplasmic reticulum (ER) through an interaction with Zeste-White 10 (ZW10). We have isolated a novel interaction between Rint1 and the human papillomavirus 16 (HPV16) transcription and replication factor E2. E2 binds to Rint1 within its ZW10 interaction domain, and we show that in the absence of E2, Rint1 is localized to the ER and associates with ZW10. E2 expression results in a disruption of the Rint1-ZW10 interaction and an accumulation of nuclear Rint1, coincident with a significant reduction in vesicle movement from the ER to the Golgi apparatus. Interestingly, nuclear Rint1 and members of the Mre11/Rad50/Nbs1 (MRN) complex were found in distinct E2 nuclear foci, which peaked during mid-S phase, indicating that the recruitment of Rint1 to E2 foci within the nucleus may also result in the recruitment of this DNA damage-sensing protein complex. We show that exogenous Rint1 expression enhances E2-dependent virus replication. Conversely, the overexpression of a truncated Rint1 protein that retains the E2 binding domain but not the Rad50 binding domain acts as a dominant negative inhibitor of E2-dependent HPV replication. Put together, these experiments demonstrate that the interaction between Rint1 and E2 has an important function in HPV replication.IMPORTANCE HPV infections are an important driver of many epithelial cancers, including those within the anogenital and oropharyngeal tracts. The HPV life cycle is tightly regulated and intimately linked to the differentiation of the epithelial cells that it infects. HPV replication factories formed in the nucleus are locations where viral DNA is copied to support virus persistence and amplification of

  3. Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication.

    Science.gov (United States)

    Das, Dipon; Smith, Nathan W; Wang, Xu; Richardson, Stacie L; Hartman, Matthew C T; Morgan, Iain M

    2017-08-01

    Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death. Here we demonstrate that calcein blocks HPV16 E1-E2 DNA replication via blocking the viral replication complex forming at the origin of replication. This occurs at non-toxic levels of calcein and demonstrates specificity as it does not block the ability of E2 to regulate transcription. We propose that calcein or derivatives could be developed as an anti-HPV therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Glutathione Transferase as a Potential Marker for Gut Epithelial Injury versus the Protective Role of Breast Milk sIgA in Infants with Rota Virus Gastroenteritis.

    Science.gov (United States)

    Sherif, Lobna S; Raouf, Randaa K Abdel; Sayede, Rokaya M El; Wakkadd, Amany S El; Shoaib, Ashraf R; Ali, Hanan M; Refay, Amira S El

    2015-12-15

    Secretory immunoglobulin A (SIgA) plays an important protective role in the recognition and clearance of enteric pathogens. This study was designed to assess if mucosal integrity "measured by secretory IgA (SIgA)" is a protective factor from more epithelial alteration "measured by glutathione transferase" in infants with Rota gastroenteritis and its relation to infants' feeding pattern. This study was conducted on 79 infants aged 6 months and less from those diagnosed as having gastroenteritis and admitted to Gastroenteritis Department in Abo El Rish Pediatric Hospital, Cairo University. Plasma glutathione s-transferases and Stool SIgA were measured using ELISA technique. Rota virus detection was done by Reverse transcriptase PCR. SIgA was found to be significantly positive in exclusive breast fed infants, Glutathione transferase was significantly more frequently positive in Rota positive cases than Rota negative cases by Reverse transcriptase PCR. A significant negative correlation between Glutathione transferase and Secretory IgA was found, (p Rota viral gastroenteritis.

  5. The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity

    Science.gov (United States)

    Duev-Cohen, Alexandra; Bar-On, Yotam; Glasner, Ariella; Berhani, Orit; Ophir, Yael; Levi-Schaffer, Francesca; Mandelboim, Michal; Mandelboim, Ofer

    2016-01-01

    Natural Killer (NK) cells are critical in the defense against viruses in general and against influenza in particular. We previously demonstrated that the activating NK cell receptor NKp46 is involved in the killing of influenza-virus infected cells through its interaction with viral hemagglutinin (HA). Furthermore, the recognition by NKp46 and consequent elimination of influenza infected cells were determined to be sialic-acid dependent. Here, we show that the human co-activating receptors 2B4 and NTB-A directly recognize the viral HA protein and co-stimulate killing by NK cells. We demonstrate that the 2B4/NTB-A-HA interactions require the sialylation of these receptors, and we identified the binding sites mediating these interactions. We also show that the virus counters these interactions through its neuraminidase (NA) protein. These results emphasize the critical role played by NK cells in eliminating influenza, a significant cause of worldwide morbidity and mortality. PMID:26919106

  6. Breast Milk Human Cytomegalovirus (CMV) Viral Load and the Establishment of Breast Milk CMV-pp65-Specific CD8 T Cells in Human CMV Infected Mothers.

    Science.gov (United States)

    Moylan, David C; Pati, Sunil K; Ross, Shannon A; Fowler, Karen B; Boppana, Suresh B; Sabbaj, Steffanie

    2017-11-27

    The role of human cytomegalovirus (HCMV)-specific T-cell responses in breast milk of HCMV-seropositive mothers is not well defined. In these studies, we demonstrate that the frequency of cytomegalovirus (CMV)-pp65-specific T-cell responses in peripheral blood mononuclear cells (PBMCs) and breast milk cells (BMCs) is increased for CD8+ T cells in both sample sources when compared with CD4+ T cells. The frequency of pp55-specific CD8 T cells producing interferon γ (IFN-γ) alone or dual IFN-γ/granzyme rB producers is increased in breast milk compared with PBMCs. Lastly, we observed a positive correlation between breast milk viral load and the CD8 pp65-specific response, suggesting that local virus replication drives antigen-specific CD8 T cells into the breast. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  7. Gravimetric Viral Diagnostics: QCM Based Biosensors for Early Detection of Viruses

    Directory of Open Access Journals (Sweden)

    Adeel Afzal

    2017-02-01

    Full Text Available Viruses are pathogenic microorganisms that can inhabit and replicate in human bodies causing a number of widespread infectious diseases such as influenza, gastroenteritis, hepatitis, meningitis, pneumonia, acquired immune deficiency syndrome (AIDS etc. A majority of these viral diseases are contagious and can spread from infected to healthy human beings. The most important step in the treatment of these contagious diseases and to prevent their unwanted spread is to timely detect the disease-causing viruses. Gravimetric viral diagnostics based on quartz crystal microbalance (QCM transducers and natural or synthetic receptors are miniaturized sensing platforms that can selectively recognize and quantify harmful virus species. Herein, a review of the label-free QCM virus sensors for clinical diagnostics and point of care (POC applications is presented with major emphasis on the nature and performance of different receptors ranging from the natural or synthetic antibodies to selective macromolecular materials such as DNA and aptamers. A performance comparison of different receptors is provided and their limitations are discussed.

  8. Prevalence of hepatitis B, hepatitis C and human immunodeficiency viral infections in patients with inflammatory bowel disease in north India

    Directory of Open Access Journals (Sweden)

    Parnita Harsh

    2017-01-01

    Full Text Available Background/Aims: Patients with inflammatory bowel disease (IBD often require immunosuppressive therapy and blood transfusions and therefore are at a high risk of contracting infections due to hepatitis B (HBV and hepatitis C (HCV and human immunodeficiency virus (HIV. In the present study, we assessed the prevalence of these infections in patients with IBD.Methods: This retrospective study included 908 consecutive patients with IBD (ulcerative colitis [UC], n=581; Crohn's disease [CD], n=327 who were receiving care at a tertiary care center. Ninety-five patients with intestinal tuberculosis (ITB were recruited as disease controls. Prospectively maintained patient databases were reviewed for the prevalence of HBV surface antigen, anti-HCV antibodies, and HIV (enzyme-linked immunosorbent assay method. HCV RNA was examined in patients who tested positive for anti-HCV antibodies. Prevalence data of the study were compared with that of the general Indian population (HBV, 3.7%; HCV, 1%; HIV, 0.3%.Results: The prevalence of HBV, HCV, and HIV was 2.4%, 1.4%, and 0.1%, respectively, in the 908 patients with IBD. Among the 581 patients with UC, 2.2% (12/541 had HBV, 1.7% (9/517 had HCV, and 0.2% (1/499 had HIV. Among the 327 patients with CD, 2.8% (8/288 had HBV, 0.7% (2/273 had HCV, and 0% (0/277 had HIV. One patient with CD had HBV and HCV coinfection. The prevalence of HBV, HCV, and HIV in patients with ITB was 5.9% (4/67, 1.8% (1/57, and 1.2% (1/84, respectively.Conclusions: The prevalence of HBV, HCV, and HIV in north Indian patients with IBD is similar to the prevalence of these viruses in the general community. Nonetheless, the high risk of flare after immunosuppressive therapy mandates routine screening of patients with IBD for viral markers.

  9. Synergistic effect of viral load and alcohol consumption on the risk of persistent high-risk human papillomavirus infection.

    Directory of Open Access Journals (Sweden)

    Hea Young Oh

    Full Text Available PURPOSE: This prospective study aimed to examine the combined effect of viral load and alcohol consumption on the risk of persistent high-risk (HR human papillomavirus (HPV infection. METHODS: Among women undergoing health screening between 2002 and 2011 at the National Cancer Center, 284 and 122 women with HR-HPV infection and cytological findings of low-grade squamous intraepithelial or lower-grade lesions were followed up for 1 and 2 years, respectively. Multivariate logistic regression analysis was performed, and the relative excess risk due to interaction (RERI and synergy index (S were calculated. RESULTS: Among drinkers, the risks of 1-year (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.05-8.18 and 2-year persistence (OR 8.08, CI 2.36-27.6 were significantly higher for high HPV loads than for low HPV loads; this association was not seen for non-drinkers. The risks for 1-year (OR 4.14, CI 1.89-9.05 and 2-year persistence (OR 6.61, CI 2.09-20.9 were significantly higher in subjects with a high HPV load who were also drinkers than in those who were non-drinkers. A high HPV load together with a longer drinking duration or higher alcohol consumption was associated with increased risks of 1-year (OR 3.07, CI 1.40-6.75 or OR 2.05, CI 0.87-4.83 and 2-year persistence (OR 6.40, CI 1.72-23.8 or OR 4.14, CI 1.18-14.6. The synergistic effect of alcohol consumption and HR-HPV load was stronger on the risk of 2-year persistence (RERI = 3.26, S = 2.38 than on the risk of 1-year persistence (RERI = 1.21, S = 1.63. CONCLUSIONS: The synergistic effect of HR-HPV load and alcohol consumption was associated with the risk of HR-HPV persistence and was stronger for longer-term HR-HPV infection. Limiting alcohol consumption might be an important measure to prevent the development of cervical cancer in women with a high HR-HPV load.

  10. Evaluation of extraction methods from paraffin wax embedded tissues for PCR amplification of human and viral DNA

    OpenAIRE

    Chan, P; Chan, D.; To, K; Yu, M.; Cheung, J.; Cheng, A

    2001-01-01

    Aim—To evaluate the efficiency of phenol/chloroform, microwave, and Qiagen spin column based DNA extractions from paraffin wax embedded tissue for use in the polymerase chain reaction (PCR). In addition, to assess the reliability of amplifying a housekeeping gene to indicate successful viral DNA extraction.

  11. “Infectobesity: viral infections (especially with human adenovirus-36: Ad-36) may be a cause of obesity

    NARCIS (Netherlands)

    Ginneken, van V.J.T.; Sitnyakowsky, L.; Jeffery, J.E.

    2009-01-01

    In recent years viral infections have been recognized as possible cause of obesity, alongside the traditionally recognized causes (genetic inheritance, and behaviour/environmental causes such as diet exercise, cultural practices and stress). Although four viruses have been reported to induce obesity

  12. 75 FR 34146 - Draft Guideline for the Prevention and Control of Norovirus Gastroenteritis Outbreaks in...

    Science.gov (United States)

    2010-06-16

    ... of Norovirus Gastroenteritis Outbreaks in Healthcare Settings AGENCY: Centers for Disease Control and... for the Prevention and Control of Norovirus Gastroenteritis Outbreaks in Healthcare Settings...-based recommendations for prevention and control of norovirus outbreaks in healthcare settings. DATES...

  13. Management strategies in the treatment of neonatal and pediatric gastroenteritis

    Directory of Open Access Journals (Sweden)

    Ciccarelli S

    2013-10-01

    Full Text Available Simona Ciccarelli,1 Ilaria Stolfi,1 Giuseppe Caramia2 1Neonatal Intensive Care Unit, Sapienza University of Rome, Rome, Italy; 2Division of Neonatology and Pediatrics, Maternal and Child Hospital "G. Salesi", Ancona, Italy Abstract: Acute gastroenteritis, characterized by the onset of diarrhea with or without vomiting, continues to be a major cause of morbidity and mortality in children in mostly resource-constrained nations. Although generally a mild and self-limiting disease, gastroenteritis is one of the most common causes of hospitalization and is associated with a substantial disease burden. Worldwide, up to 40% of children aged less than 5 years with diarrhea are hospitalized with rotavirus. Also, some microorganisms have been found predominantly in resource-constrained nations, including Shigella spp, Vibrio cholerae, and the protozoan infections. Prevention remains essential, and the rotavirus vaccines have demonstrated good safety and efficacy profiles in large clinical trials. Because dehydration is the major complication associated with gastroenteritis, appropriate fluid management (oral or intravenous is an effective and safe strategy for rehydration. Continuation of breastfeeding is strongly recommended. New treatments such as antiemetics (ondansetron, some antidiarrheal agents (racecadotril, and chemotherapeutic agents are often proposed, but not yet universally recommended. Probiotics, also known as “food supplement,” seem to improve intestinal microbial balance, reducing the duration and the severity of acute infectious diarrhea. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Society of Paediatric Infectious Diseases guidelines make a stronger recommendation for the use of probiotics for the management of acute gastroenteritis, particularly those with documented efficacy such as Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Saccharomyces boulardii. To date, the

  14. Stresshyperglykaemi hos et barn med svaer akut gastroenteritis

    DEFF Research Database (Denmark)

    Bjerre, Jesper V.

    2002-01-01

    A case of a two years and ten months old girl with severe acute gastroenteritis, dehydration, and hyperglycaemia is described. Transient hyperglycaemia is a common clinical finding in children under stress. We discuss the distinction between hyperglycaemia as a prediabetic state and that as a phy......A case of a two years and ten months old girl with severe acute gastroenteritis, dehydration, and hyperglycaemia is described. Transient hyperglycaemia is a common clinical finding in children under stress. We discuss the distinction between hyperglycaemia as a prediabetic state...... and that as a physiological response to stress during acute illness. Udgivelsesdato: 2002-Nov-18...

  15. An interaction domain in human SAMD9 is essential for myxoma virus host-range determinant M062 antagonism of host anti-viral function.

    Science.gov (United States)

    Nounamo, Bernice; Li, Yibo; O'Byrne, Peter; Kearney, Aoife M; Khan, Amir; Liu, Jia

    2017-03-01

    In humans, deleterious mutations in the sterile α motif domain protein 9 (SAMD9) gene are associated with cancer, inflammation, weakening of the immune response, and developmental arrest. However, the biological function of SAMD9 and its sequence-structure relationships remain to be characterized. Previously, we found that an essential host range factor, M062 protein from myxoma virus (MYXV), antagonized the function of human SAMD9. In this study, we examine the interaction between M062 and human SAMD9 to identify regions that are critical to SAMD9 function. We also characterize the in vitro kinetics of the interaction. In an infection assay, exogenous expression of SAMD9 N-terminus leads to a potent inhibition of wild-type MYXV infection. We reason that this effect is due to the sequestration of viral M062 by the exogenously expressed N-terminal SAMD9 region. Our studies reveal the first molecular insight into viral M062-dependent mechanisms that suppress human SAMD9-associated antiviral function. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Investigation of the Enteric Adenovirus Antigen Frequency by Immunochromotographic Method in Children with Acute Gastroenteritis

    OpenAIRE

    Orhan Akpınar; Hatice Akpınar

    2017-01-01

    Objective: Gastroenteritis is the third common cause of death due to infections. After rotavirus, adenoviruses are also one of the reasons frequently seen in gastroenteritis in infants and children. This study is performed to determine the incidence of enteric virus serotype 40 and 41 in children with acute gastroenteritis in order to enable prompt and appropriate treatment. Materials and Methods: Stool specimens of patients who attended our clinic with a diagnosis of acute gastroenteritis...

  17. [Viral superantigens].

    Science.gov (United States)

    Us, Dürdal

    2016-07-01

    Superantigens (SAgs) are microbial proteins produced by various microorganisms that elicit excessive and strong stimulation of T cells via an unconventional mechanism. They cause polyclonal activation of T cells in a non-specific manner, by binding to a particular variable-beta (Vβ) chain of T-cell receptor (TCR) and MHC class II molecule, in unprocessed form and outside of peptide-binding cleft, forming a bridge between the antigen presenting cell and the T cell. SAgs are classified into three groups, namely 1) exogenous (soluble proteins and exotoxins secreted by microorganisms), 2) endogenous (transmembrane proteins encoded by viruses which are integrated into the genome) and 3) B-cell SAgs (proteins which stimulate predominantly B cells). The best characterized and mostly studied SAgs are staphylococcal and streptococcal exotoxins, however it is well-known that many other microorganisms also possess SAg activities. Despite the presence of several viruses that cause severe infections in humans, the number of viruses that have proteins identified with SAg property in their pathogenesis, is relatively low. To date, the defined viruses that encoded SAgs are as follows; mouse mammary tumor virus (MMTV) (Marrack, et al. 1991), rabies virus (Lafon, et al. 1992), Epstein-Barr virus (EBV) (Sutkowski, et al. 1996), human endogenous retrovirus (HERV) (Conrad, et al. 1997), human immunodeficiency virus (HIV) (Posnett, et al. 1995; Torres, et al. 1996; Townsley-Fuchs, et al. 1997) and Ebola virus (Leroy, et al. 2011). SAgs were first described in the MMTV, a polymorphic B-type retrovirus that is either contained in the genome as an endogenous provirus (germline transmission) or exogenous infectious virus that transmits vertically via breast milk. Both MMTV forms encode SAgs. The SAg-mediated massive T cell activation is required for the spread of exogenous MMTV from intestines to mammary glands, facilitating the transmission of infectious virus. On the other hand

  18. Assessment the risk factors of gastroenteritis and the role of antibiotics used Ampicillin and Ampicillin plus Amikacin in the treatment among children aged 3-60 months from 1-7-2013 to 1-10 2013 in Kamal Odwan Hospital, prospective study.

    Directory of Open Access Journals (Sweden)

    Hashem M. Mansour

    2014-08-01

    Full Text Available The term gastroenteritis denotes infections of the gastrointestinal (GI tract caused by bacterial, viral, parasitic pathogens or chemical agents and food intolerance, none of which requires antimicrobial therapy. The broad principles of management of acute gastroenteritis in children include oral rehydration therapy, enteral feeding and diet selection, zinc supplementation, and additional therapies such as probiotics. Dehydration must be evaluated rapidly and corrected in 4-6 hr according to the degree of dehydration. Probiotics and mdash;used as an adjunct to oral rehydration therapy and mdash;decreased the duration of diarrhea, especially in rotavirus gastroenteritis. Early refeeding reduces the duration of diarrhea. The aim of this study is to evaluate the risk factors associated with diarrhea and the antibiotic used ampicillin and ampicillin plus amikacin in the treatment of inpatient children with acute gastroenteritis. [Cukurova Med J 2014; 39(4.000: 697-704

  19. [Toll-like receptors expression in the lungs of human metapneumovirus infected mice and the effects of polyI:C on viral infection].

    Science.gov (United States)

    Dou, Ying; Zhao, Yao; Zhang, Zhi-Yong; Zhao, Xiao-Dong

    2010-01-01

    To investigate the expression changes of Toll-like receptors (TLR) in the lungs of human metapneumovirus infected BALB/c mice, and to explore the effects of PolyI:C on viral replication, HMPV-infected group, PolyI:C+hMPV group, PolyI:C+DMED group and DMEM control group were set up for this study. All mice were sacrificed on day 1, 3, 5, 7, 9 and 16 post inoculation. Lungs were used for viral titration, pulmonary histopathology and detection of TLRs mRNA expression by RT-PCR and real-time PCR. Results showed that the levels of viral replication in the lungs of PolyI:C+hMPV infected mice were significantly decreased and lung inflammation were also lessened compared with those of hMPV infected mice. RT-PCR detection showed that mRNA levels of most TLRs were up-regulated (P lungs of hMPV infected group compared with DMEM group. Real time PCR assay showed that TLR7-8 mRNA significantly increased in hMPV infected group in a time-dependent manner. The level of TLR3 mRNA was significantly up-regulated in PolyI:C+hMPV group at the 24 hour after intranasal inoculation. The results showed that hMPV infection up-regulated the expression of TLRs in lungs of BALB/c mice and TLR7/8 pathway might play an important role in the start of natural immune response. PolyI:C was capable of inhibiting viral replication in the lung of mice and reducing lung inflammation probably through the early activation of TLR3.

  20. Viral epigenetics.

    Science.gov (United States)

    Milavetz, Barry I; Balakrishnan, Lata

    2015-01-01

    DNA tumor viruses including members of the polyomavirus, adenovirus, papillomavirus, and herpes virus families are presently the subject of intense interest with respect to the role that epigenetics plays in control of the virus life cycle and the transformation of a normal cell to a cancer cell. To date, these studies have primarily focused on the role of histone modification, nucleosome location, and DNA methylation in regulating the biological consequences of infection. Using a wide variety of strategies and techniques ranging from simple ChIP to ChIP-chip and ChIP-seq to identify histone modifications, nuclease digestion to genome wide next generation sequencing to identify nucleosome location, and bisulfite treatment to MeDIP to identify DNA methylation sites, the epigenetic regulation of these viruses is slowly becoming better understood. While the viruses may differ in significant ways from each other and cellular chromatin, the role of epigenetics appears to be relatively similar. Within the viral genome nucleosomes are organized for the expression of appropriate genes with relevant histone modifications particularly histone acetylation. DNA methylation occurs as part of the typical gene silencing during latent infection by herpesviruses. In the simple tumor viruses like the polyomaviruses, adenoviruses, and papillomaviruses, transformation of the cell occurs via integration of the virus genome such that the virus's normal regulation is disrupted. This results in the unregulated expression of critical viral genes capable of redirecting cellular gene expression. The redirected cellular expression is a consequence of either indirect epigenetic regulation where cellular signaling or transcriptional dysregulation occurs or direct epigenetic regulation where epigenetic cofactors such as histone deacetylases are targeted. In the more complex herpersviruses transformation is a consequence of the expression of the viral latency proteins and RNAs which again can

  1. Genetic imprint of vaccination on simian/human immunodeficiency virus type 1 transmitted viral genomes in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Mariana Varela

    Full Text Available Understanding the genetic, antigenic and structural changes that occur during HIV-1 infection in response to pre-existing immunity will facilitate current efforts to develop an HIV-1 vaccine. Much is known about HIV-1 variation at the population level but little with regard to specific changes occurring in the envelope glycoprotein within a host in response to immune pressure elicited by antibodies. The aim of this study was to track and map specific early genetic changes occurring in the viral envelope gene following vaccination using a highly controlled viral challenge setting in the SHIV macaque model. We generated 449 full-length env sequences from vaccinees, and 63 from the virus inoculum. Analysis revealed a different pattern in the distribution and frequency of mutations in the regions of the envelope gene targeted by the vaccine as well as different patterns of diversification between animals in the naïve control group and vaccinees. Given the high stringency of the model it is remarkable that we were able to identify genetic changes associated with the vaccination. This work provides insight into the characterization of breakthrough viral populations in less than fully efficacious vaccines and illustrates the value of HIV-1 Env SHIV challenge model in macaques to unravel the mechanisms driving HIV-1 envelope genetic diversity in the presence of vaccine induced-responses.

  2. Pathogenetic Substantiation of Optimization of Treatment for Viral Diarrheas in Children with Spore-Forming Self-Eliminating Bacteria

    Directory of Open Access Journals (Sweden)

    O.K. Koloskova

    2016-11-01

    Full Text Available This article has shown efficacy of Subalinum as probiotic drug that belongs to a group of self-eliminating antagonists. Subalinum is a recombinant bacillary probiotic strain, one dose of which contains 1·109–8·109 living microbial cells of B.subtilis 23–35/105, obtained by the introduction of plasmid DNA. This results in increased synthesis of extracellular α2 human interferon with high antagonistic activity of master strain against pathogenic and opportunistic microorganisms. Due to antiviral efficacy conditioned by interferon-inducing properties, probiotic agent Subalinum was effective in ophthalmology, in the treatment of viral hepatitis and acute intestinal infections in children. Therapeutic effect of Subalinum is determined by living bacteria, which have a high antagonistic activity against pathogenic and opportunistic microorganisms and promote normalization of qualitative and quantitative composition of intestinal microflora. Prescription of Subalinum improves the efficacy of integrated treatment for viral diseases in children, in particular viral gastroenteritis.

  3. Alpha interferon-induced antiretroviral activities: restriction of viral nucleic acid synthesis and progeny virion production in human immunodeficiency virus type 1-infected monocytes.

    OpenAIRE

    Baca-Regen, L; Heinzinger, N; Stevenson, M; Gendelman, H E

    1994-01-01

    Alpha interferon (IFN-alpha) restricts multiple steps of the human immunodeficiency virus type 1 (HIV-1) life cycle. A well-described effect of IFN-alpha is in the modulation of viral nucleic acid synthesis. We demonstrate that IFN-alpha influences HIV-1 DNA synthesis principally by reducing the production of late products of reverse transcription. The magnitude of IFN-alpha-induced downregulation of HIV-1 DNA and/or progeny virion production was dependent on the IFN-alpha concentration, the ...

  4. Local CD4 and CD8 T-cell reactivity to HSV-1 antigens documents broad viral protein expression and immune competence in latently infected human trigeminal ganglia.

    Directory of Open Access Journals (Sweden)

    Monique van Velzen

    2013-08-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 infection results in lifelong chronic infection of trigeminal ganglion (TG neurons, also referred to as neuronal HSV-1 latency, with periodic reactivation leading to recrudescent herpetic disease in some persons. HSV-1 proteins are expressed in a temporally coordinated fashion during lytic infection, but their expression pattern during latent infection is largely unknown. Selective retention of HSV-1 reactive T-cells in human TG suggests their role in controlling reactivation by recognizing locally expressed HSV-1 proteins. We characterized the HSV-1 proteins recognized by virus-specific CD4 and CD8 T-cells recovered from human HSV-1-infected TG. T-cell clusters, consisting of both CD4 and CD8 T-cells, surrounded neurons and expressed mRNAs and proteins consistent with in situ antigen recognition and antiviral function. HSV-1 proteome-wide scans revealed that intra-TG T-cell responses included both CD4 and CD8 T-cells directed to one to three HSV-1 proteins per person. HSV-1 protein ICP6 was targeted by CD8 T-cells in 4 of 8 HLA-discordant donors. In situ tetramer staining demonstrated HSV-1-specific CD8 T-cells juxtaposed to TG neurons. Intra-TG retention of virus-specific CD4 T-cells, validated to the HSV-1 peptide level, implies trafficking of viral proteins from neurons to HLA class II-expressing non-neuronal cells for antigen presentation. The diversity of viral proteins targeted by TG T-cells across all kinetic and functional classes of viral proteins suggests broad HSV-1 protein expression, and viral antigen processing and presentation, in latently infected human TG. Collectively, the human TG represents an immunocompetent environment for both CD4 and CD8 T-cell recognition of HSV-1 proteins expressed during latent infection. HSV-1 proteins recognized by TG-resident T-cells, particularly ICP6 and VP16, are potential HSV-1 vaccine candidates.

  5. A non-enteric adenovirus A12 gastroenteritis outbreak in Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Silvana Augusta Rodrigues Portes

    2016-06-01

    Full Text Available A gastroenteritis outbreak that occurred in 2013 in a low-income community in Rio de Janeiro was investigated for the presence of enteric viruses, including species A rotavirus (RVA, norovirus (NoV, astrovirus (HAstV, bocavirus (HBoV, aichivirus (AiV, and adenovirus (HAdV. Five of nine stool samples (83% from patients were positive for HAdV, and no other enteric viruses were detected. Polymerase chain reaction products were sequenced and subjected to phylogenetic analysis, which revealed four strains and one strain of non-enteric HAdV-A12 and HAdV-F41, respectively. The HAdV-A12 nucleotide sequences shared 100% nucleotide similarity. Viral load was assessed using a TaqMan real-time PCR assay. Stool samples that were positive for HAdV-A12 had high viral loads (mean 1.9 X 107 DNA copies/g stool. All four patients with HAdV-A12 were < 25 months of age and had symptoms of fever and diarrhoea. Evaluation of enteric virus outbreaks allows the characterisation of novel or unique diarrhoea-associated viruses in regions where RVA vaccination is routinely performed.

  6. First-year Daycare and Incidence of Acute Gastroenteritis

    NARCIS (Netherlands)

    Hullegie, Saskia|info:eu-repo/dai/nl/413662977; Bruijning-Verhagen, Patricia|info:eu-repo/dai/nl/353785652; Uiterwaal, Cuno S P M|info:eu-repo/dai/nl/136603947; van der Ent, Cornelis K|info:eu-repo/dai/nl/164028536; Smit, Henriette A|info:eu-repo/dai/nl/067730043; de Hoog, Marieke L A|info:eu-repo/dai/nl/314446885

    2016-01-01

    BACKGROUND: Daycare attendance has been associated with increased acute gastroenteritis (AGE) incidence in the first years of life. We investigated the effects of first-year daycare attendance on AGE incidence and primary care contact rate up to age 6 years. METHODS: Children enrolled in the

  7. How to Predict Oral Rehydration Failure in Children With Gastroenteritis

    NARCIS (Netherlands)

    D.H.F. Geurts (Dorien); E.W. Steyerberg (Ewout); H.A. Moll (Henriëtte); R. Oostenbrink (Rianne)

    2017-01-01

    textabstractOBJECTIVES:: Oral rehydration is the standard in most current guidelines for young children with acute gastroenteritis (AGE). Failure of oral rehydration can complicate the disease course, leading to morbidity due to severe dehydration. We aimed to identify prognostic factors of oral

  8. Risk Factors for Norovirus Gastroenteritis among Nicaraguan Children.

    Science.gov (United States)

    Gruber, Joann F; Bowman, Natalie M; Becker-Dreps, Sylvia; Reyes, Yaoska; Belson, Connor; Michaels, Kenan C; Bucardo, Filemon

    2017-09-01

    Norovirus is a leading cause of pediatric gastroenteritis. Understanding norovirus epidemiology is essential for reducing disease burden. We conducted a case-control study to describe the distribution, clinical features, and risk factors of norovirus gastroenteritis among children norovirus and controls were children living in the cases' communities. Study staff interviewed mothers of enrolled cases and controls to obtain detailed exposure information including food, water, and sanitation sources; recent exposures; household characteristics; and handwashing practices. In addition, study staff requested stool samples to be tested for norovirus from select household members. We used descriptive statistics to understand the epidemiologic and clinical features of gastroenteritis episodes. To analyze potential risk factors, we used Firth's penalized logistic regression to estimate crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs). There were 102 children with gastroenteritis, 18 cases of norovirus and 31 controls. Norovirus cases occurred later in the year, corresponding to a delay in the rainy season. Cases were more likely to have a household member with norovirus in their stool as compared with controls [crude OR: 13.3 (95% CI: 2.5, 136.2) and adjusted OR: 11.5 (95% CI: 1.6, 223.2)]. In addition, alcohol-based hand sanitizer use among household members was reported for 10 (32%) of controls and but never for cases. Further research is needed to understand household transmission of norovirus in low- and middle-income countries and the potential impact of hand sanitizer use.

  9. Outbreaks of gastroenteritis linked to lettuce, Denmark, January 2010

    DEFF Research Database (Denmark)

    Ethelberg, S.; Lisby, M.; Bottiger, B.

    2010-01-01

    At least 11 linked outbreaks of gastroenteritis with a total of 260 cases have occurred in Denmark in mid January 2010. Investigations showed that the outbreaks were caused by norovirus of several genotypes and by enterotoxigenic Escherichia coli. Lettuce of the lollo bionda type grown in France...

  10. Incidence of pneumonia and gastroenteritis among infants admitted ...

    African Journals Online (AJOL)

    Introduction. Pneumonia and gastroenteritis are the leading causes of preventable childhood morbidity and mortality representing more than one third of mortality among children less than 5 years of age globally 1. Mortality from pneumonia among American children decreased by more than 90% from 1939 to 1996 largely.

  11. Jaarlijkse reunie loopt uit op een gastro-enteritis explosie

    NARCIS (Netherlands)

    Carsauw HHC; Bosman A; Reintjes R; de Wit MAS; Conyn-van Spaendonck MAE; CIE; GGD Rotterdam e.o.

    1997-01-01

    Een explosie van acute gastro-enteritis deed zich voor onder 200 deelnemers aan een reunie van oud-personeelsleden. De reunie vond plaats in een restaurant. Om de oorzaak van de explosie en de mogelijke rol van voedsel hierbij te achterhalen werd een retrospectieve cohort studie opgezet.

  12. Escherichia coli Meningitis after Rotavirus Gastroenteritis in an Infant.

    Science.gov (United States)

    Ozgurhan, Gamze; Vermezoglu, Oznur; Ocal Topcu, Didem; Karbuz, Adem; Vehapoglu, Aysel; Hacihamdioglu, Bulent

    2016-01-01

    Although rotavirus gastroenteritis is quite common in the pediatric population, secondary bacterial sepsis following rotavirus infection is a rare clinical entity. Gram-negative bacilli are the fifth most common cause of meningitis in infants but this infection rarely occurs after gastroenteritis. Here, we report a 2.5-month-old infant who developed Escherichia coli (E. coli) meningitis after acute rotavirus gastroenteritis. The 2.5-month-old male infant with fever, vomiting, and watery diarrhea that started 1 day earlier was admitted to the hospital. Rotavirus antigen in stool sample was positive. He was hospitalized, and fever was measured at 39.5°C on the second day. Lumbar puncture was done for suspicion of meningitis, and cerebrospinal fluid (CSF) findings suggested meningitis. Intravenous vancomycin and cefotaxime were started empirically. Since E. coli reproduction was seen in blood culture and CSF culture, treatment was continued with cefotaxime. The patient was discharged with minimal midlevel hydrocephalus findings in cranial ultrasonography and magnetic resonance imaging following 21 days of antibiotics treatment. Septicemia development following rotavirus gastroenteritis is an extremely rare clinical condition. It is vital to start prompt antibiotic treatment as soon as the diagnosis of secondary bacterial infection is made because of high mortality and morbidity rates.

  13. Listeria monocytogenes Meningitis Complicating Rotavirus Gastroenteritis in an Immunocompetent Child.

    Science.gov (United States)

    Ohnishi, Takuma; Kawano, Akiko; Araki, Mayumi; Hamahata, Yuko; Usui, Machiko; Shimoyamada, Motoko; Tamame, Takuya; Akashi, Masayuki; Sato, Seiji

    2017-06-25

    Listeria monocytogenes only occasionally causes bacterial meningitis in immunocompetent children. We report a case of L. monocytogenes meningitis associated with rotavirus gastroenteritis. The patient was a previously healthy 20-month-old girl who was admitted because of sustained fever and lethargy after suffering from gastroenteritis for 6 days. The patient's peripheral white blood cell count was 18,600/µL and the C-reactive protein level was 2.44 mg/dL. A stool sample tested positive for rotavirus antigen. A cerebrospinal fluid (CSF) sample showed pleocytosis. Cultures of the CSF and stool samples revealed the presence of L. monocytogenes. The patient was successfully treated with ampicillin and gentamicin. We speculate that translocation of enteric flora across the intestinal epithelium that had been damaged by rotavirus gastroenteritis might have caused bacteremia that disseminated into the CSF. Both listeriosis and secondary systemic infection after rotavirus gastroenteritis are rare but not unknown. Initiation of appropriate treatment as soon as possible is important for all types of bacterial meningitis. This rare but serious complication should be taken into consideration even if the patient does not have any medical history of immune-related problems.

  14. Escherichia coli Meningitis after Rotavirus Gastroenteritis in an Infant

    Directory of Open Access Journals (Sweden)

    Gamze Ozgurhan

    2016-01-01

    Full Text Available Although rotavirus gastroenteritis is quite common in the pediatric population, secondary bacterial sepsis following rotavirus infection is a rare clinical entity. Gram-negative bacilli are the fifth most common cause of meningitis in infants but this infection rarely occurs after gastroenteritis. Here, we report a 2.5-month-old infant who developed Escherichia coli (E. coli meningitis after acute rotavirus gastroenteritis. The 2.5-month-old male infant with fever, vomiting, and watery diarrhea that started 1 day earlier was admitted to the hospital. Rotavirus antigen in stool sample was positive. He was hospitalized, and fever was measured at 39.5°C on the second day. Lumbar puncture was done for suspicion of meningitis, and cerebrospinal fluid (CSF findings suggested meningitis. Intravenous vancomycin and cefotaxime were started empirically. Since E. coli reproduction was seen in blood culture and CSF culture, treatment was continued with cefotaxime. The patient was discharged with minimal midlevel hydrocephalus findings in cranial ultrasonography and magnetic resonance imaging following 21 days of antibiotics treatment. Septicemia development following rotavirus gastroenteritis is an extremely rare clinical condition. It is vital to start prompt antibiotic treatment as soon as the diagnosis of secondary bacterial infection is made because of high mortality and morbidity rates.

  15. Incidence of pneumonia and gastroenteritis among infants admitted ...

    African Journals Online (AJOL)

    A retrospective study based on medical records of infants admitted to the Orotta Paediatric Teaching Hospital for the whole of 2006 in order to study the morbidity and mortality rates from pneumonia and gastroenteritis among infants in Eritrea using the integrated management of childhood illnesses guidelines. The main ...

  16. Importance of ICD-10 coding directive change for acute gastroenteritis (unspecified) for rotavirus vaccine impact studies: illustration from a population-based cohort study from Ontario, Canada.

    Science.gov (United States)

    Wilson, Sarah E; Deeks, Shelley L; Rosella, Laura C

    2015-09-15

    In Ontario, Canada, we conducted an evaluation of rotavirus (RV) vaccine on hospitalizations and Emergency Department (ED) visitations for acute gastroenteritis (AGE). In our original analysis, any one of the International Classification of Disease, Version 10 (ICD-10) codes was used for outcome ascertainment: RV-specific- (A08.0), viral- (A08.3, A08. 4, A08.5), and unspecified infectious- gastroenteritis (A09). Annual age-specific rates per 10,000 population were calculated. The average monthly rate of AGE hospitalization for children under age two increased from 0.82 per 10,000 from January 2003 to March 2009, to 2.35 over the period of April 2009 to March 31, 2013. Similar trends were found for ED consultations and in other age groups. A rise in events corresponding to the A09 code was found when the outcome definition was disaggregated by ICD-10 code. Documentation obtained from the World Health Organization confirmed that a change in directive for the classification of unspecified gastroenteritis occurred with the release of ICD-10 in April 2009. AGE events previously classified under the code K52.9, are now classified under code A09.9. Based on change in the classification of unspecified gastroenteritis we modified our outcome definition to also include unspecified non-infectious-gastroenteritis (K52.9). We recommend other investigators consider using both A09.9 and K52.9 ICD-10 codes for outcome ascertainment in future rotavirus vaccine impact studies to ensure that all unspecified cases of AGE are captured, especially if the study period spans 2009.

  17. Viral bronchiolitis.

    Science.gov (United States)

    Florin, Todd A; Plint, Amy C; Zorc, Joseph J

    2017-01-14

    Viral bronchiolitis is a common clinical syndrome affecting infants and young children. Concern about its associated morbidity and cost has led to a large body of research that has been summarised in systematic reviews and integrated into clinical practice guidelines in several countries. The evidence and guideline recommendations consistently support a clinical diagnosis with the limited role for diagnostic testing for children presenting with the typical clinical syndrome of viral upper respiratory infection progressing to the lower respiratory tract. Management is largely supportive, focusing on maintaining oxygenation and hydration of the patient. Evidence suggests no benefit from bronchodilator or corticosteroid use in infants with a first episode of bronchiolitis. Evidence for other treatments such as hypertonic saline is evolving but not clearly defined yet. For infants with severe disease, the insufficient available data suggest a role for high-flow nasal cannula and continuous positive airway pressure use in a monitored setting to prevent respiratory failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The impact of rotavirus gastroenteritis on the family

    Directory of Open Access Journals (Sweden)

    Kelly Claudia M

    2009-02-01

    Full Text Available Abstract Background Rotavirus is the leading cause of severe diarrhea in young children and causes substantial morbidity and mortality. Although the clinical aspects have been well described, little information is available regarding the emotional, social, and economic impact of rotavirus gastroenteritis on the family of a sick child. The objectives of this study were to: 1 assess the family impact of rotavirus gastroenteritis through qualitative interviews with parents; 2 compare the clinical severity of rotavirus-positive and negative gastroenteritis; 3 test a questionnaire asking parents to rank the importance of various factors associated with a case of rotavirus gastroenteritis. Methods The study enrolled parents and children (2–36 months of age brought to one of the study sites (outpatient clinic or ER if the child experienced ≥ 3 watery or looser-than normal stools and/or forceful vomiting within any 24-hour period within the prior 3 days. The clinical severity of each child's illness was rated using a clinical scoring system and stool samples were tested for rotavirus antigen. Parents of rotavirus-positive children were invited to participate in focus group or individual interviews and subsequently completed a questionnaire regarding the impact of their child's illness. Results Of 62 enrolled children, 43 stool samples were collected and 63% tested positive for rotavirus. Illness was more severe in children with rotavirus-positive compared to rotavirus-negative gastroenteritis (92% vs. 37.5% rated as moderate/severe. Seventeen parents of rotavirus-positive children participated in the interviews and completed the written questionnaire. Parents were frightened by the severity of vomiting and diarrhea associated with rotavirus gastroenteritis, and noted that family life was impacted in several ways including loss of sleep, missed work, and an inability to complete normal household tasks. They expressed frustration at the lack of a

  19. Norovirus and Medically Attended Gastroenteritis in U.S. Children

    Science.gov (United States)

    Payne, Daniel C.; Vinjé, Jan; Szilagyi, Peter G.; Edwards, Kathryn M.; Staat, Mary Allen; Weinberg, Geoffrey A.; Hall, Caroline B.; Chappell, James; Bernstein, David I.; Curns, Aaron T.; Wikswo, Mary; Shirley, S. Hannah; Hall, Aron J.; Lopman, Benjamin; Parashar, Umesh D.

    2015-01-01

    BACKGROUND Cases of rotavirus-associated acute gastroenteritis have declined since the introduction of rotavirus vaccines, but the burden of norovirus-associated acute gastroenteritis in children remains to be assessed. METHODS We conducted active surveillance for laboratory-confirmed cases of norovirus among children younger than 5 years of age with acute gastroenteritis in hospitals, emergency departments, and outpatient clinical settings. The children resided in one of three U.S. counties during the years 2009 and 2010. Fecal specimens were tested for norovirus and rotavirus. We calculated population-based rates of norovirus-associated acute gastroenteritis and reviewed billing records to determine medical costs; these data were extrapolated to the U.S. population of children younger than 5 years of age. RESULTS Norovirus was detected in 21% of young children (278 of 1295) seeking medical attention for acute gastroenteritis in 2009 and 2010, with norovirus detected in 22% (165 of 742) in 2009 and 20% (113 of 553) in 2010 (P = 0.43). The virus was also detected in 4% of healthy controls (19 of 493) in 2009. Rotavirus was identified in 12% of children with acute gastroenteritis (152 of 1295) in 2009 and 2010. The respective rates of hospitalization, emergency department visits, and outpatient visits for the norovirus were 8.6, 146.7, and 367.7 per 10,000 children younger than 5 years of age in 2009 and 5.8, 134.3, and 260.1 per 10,000 in 2010, with an estimated cost per episode of $3,918, $435, and $151, respectively, in 2009. Nationally, we estimate that the average numbers of annual hospitalizations, emergency department visits, and outpatient visits due to norovirus infection in 2009 and 2010 among U.S. children in this age group exceeded 14,000, 281,000, and 627,000, respectively, with more than $273 million in treatment costs each year. CONCLUSIONS Since the introduction of rotavirus vaccines, norovirus has become the leading cause of medically attended acute

  20. Management strategies in the treatment of neonatal and pediatric gastroenteritis.

    Science.gov (United States)

    Ciccarelli, Simona; Stolfi, Ilaria; Caramia, Giuseppe

    2013-10-29

    Acute gastroenteritis, characterized by the onset of diarrhea with or without vomiting, continues to be a major cause of morbidity and mortality in children in mostly resource-constrained nations. Although generally a mild and self-limiting disease, gastroenteritis is one of the most common causes of hospitalization and is associated with a substantial disease burden. Worldwide, up to 40% of children aged less than 5 years with diarrhea are hospitalized with rotavirus. Also, some microorganisms have been found predominantly in resource-constrained nations, including Shigella spp, Vibrio cholerae, and the protozoan infections. Prevention remains essential, and the rotavirus vaccines have demonstrated good safety and efficacy profiles in large clinical trials. Because dehydration is the major complication associated with gastroenteritis, appropriate fluid management (oral or intravenous) is an effective and safe strategy for rehydration. Continuation of breastfeeding is strongly recommended. New treatments such as antiemetics (ondansetron), some antidiarrheal agents (racecadotril), and chemotherapeutic agents are often proposed, but not yet universally recommended. Probiotics, also known as "food supplement," seem to improve intestinal microbial balance, reducing the duration and the severity of acute infectious diarrhea. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Society of Paediatric Infectious Diseases guidelines make a stronger recommendation for the use of probiotics for the management of acute gastroenteritis, particularly those with documented efficacy such as Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Saccharomyces boulardii. To date, the management of acute gastroenteritis has been based on the option of "doing the least": oral rehydration-solution administration, early refeeding, no testing, no unnecessary drugs.

  1. Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH/gL/pUL128-131 Pentameric Complex.

    Science.gov (United States)

    Ha, Sha; Li, Fengsheng; Troutman, Matthew C; Freed, Daniel C; Tang, Aimin; Loughney, John W; Wang, Dai; Wang, I-Ming; Vlasak, Josef; Nickle, David C; Rustandi, Richard R; Hamm, Melissa; DePhillips, Pete A; Zhang, Ningyan; McLellan, Jason S; Zhu, Hua; Adler, Stuart P; McVoy, Michael A; An, Zhiqiang; Fu, Tong-Ming

    2017-04-01

    Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a vaccinated animal, we mapped eight sites on the dominant virus-neutralizing antigen-the pentameric complex of glycoprotein H (gH), gL, and pUL128, pUL130, and pUL131. By evaluating the site-specific antibodies in vaccine immune sera, we demonstrated that vaccination elicited functional antiviral antibodies to multiple neutralizing sites in rhesus macaques, with quality attributes comparable to those of CMV hyperimmune globulin. Furthermore, these immune sera showed antiviral activities against a panel of genetically distinct HCMV clinical isolates. These results highlighted the importance of understanding the quality of vaccine-induced antibody responses, which includes not only the neutralizing potency in key cell types but also the ability to protect against the genetically diverse field strains.IMPORTANCE HCMV is the leading cause of congenital viral infection, and development of a preventive vaccine is a high public health priority. To understand the strain coverage of vaccine-induced immune responses in comparison with natural immunity, we used a panel of broadly neutralizing antibodies to identify the immunogenic sites of a dominant viral antigen-the pentameric complex. We further demonstrated that following vaccination of a replication

  2. Comparison of three multiplex gastrointestinal platforms for the detection of gastroenteritis viruses.

    Science.gov (United States)

    Chhabra, Preeti; Gregoricus, Nicole; Weinberg, Geoffrey A; Halasa, Natasha; Chappell, James; Hassan, Ferdaus; Selvarangan, Rangaraj; Mijatovic-Rustempasic, Slavica; Ward, M Leanne; Bowen, Michael; Payne, Daniel C; Vinjé, Jan

    2017-10-01

    Viruses are major etiological agents of childhood gastroenteritis. In recent years, several molecular platforms for the detection of viral enteric pathogens have become available. We evaluated the performance of three multiplex platforms including Biofire's Gastrointestinal Panel (FilmArray), Luminex xTAG ® Gastrointestinal Pathogen Panel (GPP), and the TaqMan Array Card (TAC) for the detection of five gastroenteritis viruses using a coded panel of 300 archived stool samples. The FilmArray detected a virus in 199 (96.1%) and the TAC in 172 (83.1%) of the 207 samples (187 samples positive for a single virus and 20 samples positive for more than one virus) whereas the GPP detected a virus in 100 (78.7%) of the 127 (97 positive for one virus and three positive for more than one virus) samples. Overall the clinical accuracy was highest for the FilmArray (98%) followed by TAC (97.2%) and GPP (96.9%). The sensitivity of the FilmArray, GPP and TAC platforms was highest for rotavirus (100%, 95.8%, and 89.6%, respectively) and lowest for adenovirus type 40/41 (97.4%, 57.9% and 68.4%). The specificity of the three platforms ranged from 95.6% (rotavirus) to 99.6% (norovirus/sapovirus) for the FilmArray, 99.6% (norovirus) to 100% (rotavirus/adenovirus) for GPP, and 98.9% (astrovirus) to 100% (rotavirus/sapovirus) for TAC. The FilmArray demonstrated the best analytical performance followed by TAC. In recent years, the availability of multi-enteric molecular testing platforms has increased significantly and our data highlight the strengths and weaknesses of these platforms. Published by Elsevier B.V.

  3. Evaluation of fecal calprotectin in Campylobacter concisus and Campylobacter jejuni/coli gastroenteritis.

    Science.gov (United States)

    Nielsen, Hans Linde; Engberg, Jørgen; Ejlertsen, Tove; Nielsen, Henrik

    2013-05-01

    Calprotectin (CP) is a calcium-binding cytosolic neutrophil protein and the concentration in feces reflects the migration of neutrophils into the gut lumen. Testing for fecal CP (f-CP) in patients with negative cultures for enteric pathogens is widely accepted as a useful screening tool for identifying patients who are most likely to benefit from endoscopy for suspected inflammatory bowel disease (IBD) with the assumption that a negative f-CP is compatible with a functional disorder. Campylobacter concisus has recently been reported to have a high incidence in the Danish population almost equal to Campylobacter jejuni and Campylobacter coli and has been reported to cause prolonged watery diarrhea. However, isolation of C. concisus from feces requires the filter method in a hydrogen-enriched microaerobic atmosphere, which is not commonly used in the laboratory, and the diagnosis may consequently be missed. The aim of this study was to evaluate the f-CP levels, as a marker for the intestinal inflammation in C. jejuni/coli- and C. concisus-infected patients. The authors found a high concentration of f-CP (median 631: IQR 221-1274) among 140 patients with C. jejuni/coli infection, whereas the f-CP level among 99 C. concisus-infected patients was significantly lower (median 53: IQR 20-169). The data correlate to the severe inflammatory gastroenteritis seen in patients infected with C. jejuni/coli, whereas C. concisus-infected patients have a much lower intestinal inflammation which could be compared with viral gastroenteritis. Nevertheless, clinicians should be aware of C. concisus infection, especially in patients with prolonged mild diarrhea, in the differential diagnosis to IBD.

  4. Detection of rotavirus and other enteropathogens in children hospitalized with acute gastroenteritis in Havana, Cuba.

    Science.gov (United States)

    Ribas, María de Los Angeles; Tejero, Yahisel; Cordero, Yanislet; de Los Angeles León, María; Rodriguez, Misladys; Perez-Lastre, Jorge; Triana, Thelma; Guerra, Mabel; Ayllón, Lucía; Escalante, Gladys; Hadad, Jorge

    2015-08-01

    The aim of the study was to diagnose infections with rotavirus and other enteric pathogens in children under five years old with acute gastroenteritis and to identify the most common epidemiological and clinical characteristics of these pathogens. The study was conducted using 110 stool samples from the same number of children under five years old who were inpatients at three paediatric hospitals in Havana, Cuba, between October and December 2011. The samples were tested for rotavirus and other enteric pathogens using traditional and molecular microbiological methods. Pathogens were detected in 85 (77.3 %) of the children. Rotavirus was the most commonly found, appearing in 54.5 % of the children, followed by bacteria (29 %) and parasites (10.9 %). Other viral pathogens detected included adenovirus (6.4 %) and astrovirus (3.6 %). In rotavirus-positives cases, at least one other pathogen was detected, usually a bacterium (26.6 %). More than three episodes of watery diarrhea in 24 hours were observed in 78.3 % of the cases. Dehydration was found in 30 (50 %) rotavirus-positive children, of whom seven (11.6 %) were transferred to an intensive care unit due to complications of metabolic acidosis. Rotavirus was most commonly observed among children under 12 months old (65 %). The highest incidence of infection occurred in children who were under the care of a relative at home (78.3 %), had not been breastfed (65 %), or had been breastfed for less than six months (28.3 %). The genotype combinations most frequently found were G9P8 (28.3 %) and G1P8 (10 %). This study demonstrates the presence of rotavirus and other enteric pathogens as causes of gastroenteritis in hospitalized infants and young children in Cuba.

  5. Norovirus Recombinant Strains Isolated from Gastroenteritis Outbreaks in Southern Brazil, 2004-2011.

    Science.gov (United States)

    Fumian, Tulio Machado; da Silva Ribeiro de Andrade, Juliana; Leite, José Paulo Gagliardi; Miagostovich, Marize Pereira

    2016-01-01

    Noroviruses are recognized as one of the leading causes of viral acute gastroenteritis, responsible for almost 50% of acute gastroenteritis outbreaks worldwide. The positive single-strand RNA genome of noroviruses presents a high mutation rate and these viruses are constantly evolving by nucleotide mutation and genome recombination. Norovirus recombinant strains have been detected as causing acute gastroenteritis outbreaks in several countries. However, in Brazil, only one report of a norovirus recombinant strain (GII.P7/GII.20) has been described in the northern region so far. For this study, 38 norovirus strains representative of outbreaks, 11 GII.4 and 27 non-GII.4, were randomly selected and amplified at the ORF1/ORF2 junction. Genetic recombination was identified by constructing phylogenetic trees of the polymerase and capsid genes, and further SimPlot and Bootscan analysis of the ORF1/ORF2 overlap. Sequence analysis revealed that 23 out of 27 (85%) non-GII.4 noroviruses were recombinant strains, characterized as: GII.P7/GII.6 (n = 9); GIIP.g/GII.12 (n = 4); GII.P16/GII.3 (n = 4); GII.Pe/GII.17 (n = 2); GII.P7/GII.14 (n = 1); GII.P13/GII.17 (n = 1); GII.P21/GII.3 (n = 1); and GII.P21/GII.13 (n = 1). On the other hand, among the GII.4 variants analyzed (Den Haag_2006b and New Orleans_2009) no recombination was observed. These data revealed the great diversity of norovirus recombinant strains associated with outbreaks, and describe for the first time these recombinant types circulating in Brazil. Our results obtained in southern Brazil corroborate the previous report for the northern region, demonstrating that norovirus recombinant strains are circulating more frequently than we expected. In addition, these results emphasize the relevance of including ORF1/ORF2-based analysis in surveillance studies as well as the importance of characterizing strains from other Brazilian regions to obtain epidemiological data for norovirus recombinant strains circulating in the

  6. Norovirus Recombinant Strains Isolated from Gastroenteritis Outbreaks in Southern Brazil, 2004-2011.

    Directory of Open Access Journals (Sweden)

    Tulio Machado Fumian

    Full Text Available Noroviruses are recognized as one of the leading causes of viral acute gastroenteritis, responsible for almost 50% of acute gastroenteritis outbreaks worldwide. The positive single-strand RNA genome of noroviruses presents a high mutation rate and these viruses are constantly evolving by nucleotide mutation and genome recombination. Norovirus recombinant strains have been detected as causing acute gastroenteritis outbreaks in several countries. However, in Brazil, only one report of a norovirus recombinant strain (GII.P7/GII.20 has been described in the northern region so far. For this study, 38 norovirus strains representative of outbreaks, 11 GII.4 and 27 non-GII.4, were randomly selected and amplified at the ORF1/ORF2 junction. Genetic recombination was identified by constructing phylogenetic trees of the polymerase and capsid genes, and further SimPlot and Bootscan analysis of the ORF1/ORF2 overlap. Sequence analysis revealed that 23 out of 27 (85% non-GII.4 noroviruses were recombinant strains, characterized as: GII.P7/GII.6 (n = 9; GIIP.g/GII.12 (n = 4; GII.P16/GII.3 (n = 4; GII.Pe/GII.17 (n = 2; GII.P7/GII.14 (n = 1; GII.P13/GII.17 (n = 1; GII.P21/GII.3 (n = 1; and GII.P21/GII.13 (n = 1. On the other hand, among the GII.4 variants analyzed (Den Haag_2006b and New Orleans_2009 no recombination was observed. These data revealed the great diversity of norovirus recombinant strains associated with outbreaks, and describe for the first time these recombinant types circulating in Brazil. Our results obtained in southern Brazil corroborate the previous report for the northern region, demonstrating that norovirus recombinant strains are circulating more frequently than we expected. In addition, these results emphasize the relevance of including ORF1/ORF2-based analysis in surveillance studies as well as the importance of characterizing strains from other Brazilian regions to obtain epidemiological data for norovirus recombinant strains

  7. Strategies for design and application of enteric viral vaccines.

    Science.gov (United States)

    Chattha, Kuldeep S; Roth, James A; Saif, Linda J

    2015-01-01

    Enteric viral infections in domestic animals cause significant economic losses. The recent emergence of virulent enteric coronaviruses [porcine epidemic diarrhea virus (PEDV)] in North America and Asia, for which no vaccines are available, remains a challenge for the global swine industry. Vaccination strategies against rotavirus and coronavirus (transmissible gastroenteritis virus) infections are reviewed. These vaccination principles are applicable against emerging enteric infections such as PEDV. Maternal vaccines to induce lactogenic immunity, and their transmission to suckling neonates via colostrum and milk, are critical for early passive protection. Subsequently, in weaned animals, oral vaccines incorporating novel mucosal adjuvants (e.g., vitamin A, probiotics) may provide active protection when maternal immunity wanes. Understanding intestinal and systemic immune responses to experimental rotavirus and transmissible gastroenteritis virus vaccines and infection in pigs provides a basis and model for the development of safe and effective vaccines for young animals and children against established and emerging enteric infections.

  8. Short-term garlic supplementation and highly active antiretroviral treatment adherence, CD4+ cell counts, and human immunodeficiency virus viral load.

    Science.gov (United States)

    Liu, Chenglong; Wang, Cuiwei; Robison, Esther; Levine, Alexandra M; Gandhi, Monica; Schwartz, Rebecca; Weber, Kathleen M; Merenstein, Daniel

    2012-01-01

    Human immunodeficiency virus (HIV)-infected individuals frequently have consumed garlic, a popular complementary supplement. Researchers rarely have studied garlic's association with antiretroviral therapies, however, even though that association is very relevant clinically. To examine associations of supplemental use of garlic with highly active antiretroviral treatment (HAART) adherence level and HAART effectiveness (HIV viral load and CD4+ cell counts) in HIV-infected women. The research team carried out a self-controlled, longitudinal study nested within the Women's Interagency HIV Study (WIHS). The team used a paired study design that allowed participants to serve as their own controls. The team first identified all of the studies visits in which the participant self-reported the use of a garlic supplement since her last visit (index visit). Then for each index visit, the team identified a matching visit (a control visit) using the following criteria: (a) the visit must be one for the same participant in which that participant reported no garlic supplementation; (b) the visit must immediately precede the index visit (less than 1 year apart); and (c) at the time of the control visit, the participant must have been using antiretroviral therapy identical to that used at the time of the index visit. Participants were persons using garlic supplementation who already were participants in the WIHS. The research team used a logistic regression model to examine the association between garlic supplementation and HAART adherence level. The team used a mixed linear model to examine the association of garlic supplementation with HIV viral load and CD4+ cell counts. From October 1994 to April 2009, 390 HIV-infected women in the WIHS made 1112 visits at which they reported using garlic supplements. Seventy-seven HIV-infected women using HAART met the research teams selection criteria and contributed 99 pairs of visits for the study. Among the women who used garlic

  9. Short-term Garlic Supplementation and Highly Active Antiretroviral Treatment Adherence, CD4+ Cell Counts, and Human Immunodeficiency Virus Viral Load

    Science.gov (United States)

    Liu, Chenglong; Wang, Cuiwei; Robison, Esther; Levine, Alexandra M.; Gandhi, Monica; Schwartz, Rebecca; Weber, Kathleen M.; Merenstein, Daniel

    2012-01-01

    Context Human immunodeficiency virus (HIV)–infected individuals frequently have consumed garlic, a popular complementary supplement. Researchers rarely have studied garlic’s association with antiretroviral therapies, however, even though that association is very relevant clinically. Objective To examine associations of supplemental use of garlic with highly active antiretroviral treatment (HAART) adherence level and HAART effectiveness (HIV viral load and CD4+ cell counts) in HIV-infected women. Design The research team carried out a self-controlled, longitudinal study nested within the Women’s Interagency HIV Study (WIHS). The team used a paired study design that allowed participants to serve as their own controls. The team first identified all of the study’s visits in which the participant self-reported the use of a garlic supplement since her last visit (index visit). Then for each index visit, the team identified a matching visit (a control visit) using the following criteria: (a) the visit must be one for the same participant in which that participant reported no garlic supplementation; (b) the visit must immediately precede the index visit (less than 1 year apart); and (c) at the time of the control visit, the participant must have been using antiretroviral therapy identical to that used at the time of the index visit. Participants Participants were persons using garlic supplementation who already were participants in the WIHS. Outcome Measures The research team used a logistic regression model to examine the association between garlic supplementation and HAART adherence level. The team used a mixed linear model to examine the association of garlic supplementation with HIV viral load and CD4+ cell counts. Results From October 1994 to April 2009, 390 HIV-infected women in the WIHS made 1112 visits at which they reported using garlic supplements. Seventy-seven HIV-infected women using HAART met the research team’s selection criteria and contributed 99

  10. Human papillomavirus cervical infection: viral genotyping and risk factors for high-grade squamous intraepithelial lesion and cervix cancer

    OpenAIRE

    Vilma Guimarães de Mendonça; Maria José Bezerra Guimarães; José Luiz de Lima Filho; Carolina Guimarães de Mendonça; Danyelly Bruneska Gondim Martins; Sergio Crovella; Luiz Cláudio Arraes de Alencar

    2010-01-01

    OBJETIVO: analisar, em mulheres com HPV em colo do útero, as características da infecção viral e os fatores de risco para lesão intraepitelial de alto grau e carcinoma cervical. MÉTODOS: realizou-se um estudo caso-controle com mulheres com HPV em colo do útero atendidas em serviço de Ginecologia de referência vinculado ao SUS, em Recife, Nordeste do Brasil. No grupo de casos (72 mulheres com lesão intraepitelial de alto grau ou carcinoma cervical) e de controles (176 mulheres com colpocitolog...

  11. Particulate Air Pollution Exposure and Expression of Viral and Human MicroRNAs in Blood: The Beijing Truck Driver Air Pollution Study.

    Science.gov (United States)

    Hou, Lifang; Barupal, Jitendra; Zhang, Wei; Zheng, Yinan; Liu, Lei; Zhang, Xiao; Dou, Chang; McCracken, John P; Díaz, Anaité; Motta, Valeria; Sanchez-Guerra, Marco; Wolf, Katherine Rose; Bertazzi, Pier Alberto; Schwartz, Joel D; Wang, Sheng; Baccarelli, Andrea A

    2016-03-01

    MicroRNAs (miRNAs) are post-transcriptional gene suppressors and potential mediators of environmental effects. In addition to human miRNAs, viral miRNAs expressed from latent viral sequences are detectable in human cells. In a highly exposed population in Beijing, China, we evaluated the associations of particulate air pollution exposure on blood miRNA profiles. The Beijing Truck Driver Air Pollution Study (BTDAS) included 60 truck drivers and 60 office workers. We investigated associations of short-term air pollution exposure, using measures of personal PM2.5 (particulate matter ≤ 2.5 μm) and elemental carbon (EC), and ambient PM10 (≤ 10 μm), with blood NanoString nCounter miRNA profiles at two exams separated by 1-2 weeks. No miRNA was significantly associated with personal PM2.5 at a false discovery rate (FDR) of 20%. Short-term ambient PM10 was associated with the expression of 12 miRNAs in office workers only (FDR pollution-associated health effects. PM2.5/PM10 exposures showed no consistent relationships with miRNA expression.

  12. Outbreak of Salmonella infantis gastroenteritis among people who had eaten at a hash house in southern Italy.

    Science.gov (United States)

    Chironna, M; Tafuri, S; Gallone, M S; Sallustio, A; Martinelli, D; Prato, R; Germinario, C

    2014-05-01

    To describe an outbreak of acute gastroenteritis in people who had eaten at a hash house in southern Italy. Case-control study. A clinical case of gastroenteritis was defined as a person who had eaten at the hash house from 29 August to 4 September 2011 and who experienced defined gastrointestinal symptoms within 72 hours, or a person with a laboratory-confirmed salmonella infection without symptoms. A convenience sample was enrolled as the control group. Environmental and human samples were collected, and Salmonella infantis was identified by polymerase chain reaction. Univariate analysis was performed for each food type, and multivariate analysis was performed for each food type and demographic variable (gender, age). Twenty-three cases of gastroenteritis were notified between 1 and 4 September 2011, two of which were admitted to the local hospital. Multivariate analysis showed that porchetta [odds ratio (OR) 22.0, 95% confidence interval (CI) 3.2-152.6, z = 3.13, P = 0.002] and roasted meat (OR 14.4, 95% CI 1.7-122.0, z = 2.45, P = 0.014) were associated with gastrointestinal symptoms. Environmental and human isolates exhibited the same sequence type (ST 32). This experience highlighted that, in the control of a foodborne outbreak, integrated epidemiological and laboratory surveillance enables rapid identification of the source of infection, thus reducing the risk of an epidemic. Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  13. Infection of human cancer cells with myxoma virus requires Akt activation via interaction with a viral ankyrin-repeat host range factor.

    Science.gov (United States)

    Wang, Gen; Barrett, John W; Stanford, Marianne; Werden, Steven J; Johnston, James B; Gao, Xiujuan; Sun, Mei; Cheng, Jin Q; McFadden, Grant

    2006-03-21

    We demonstrate that the susceptibility of human cancer cells to be infected and killed by an oncolytic poxvirus, myxoma virus (MV), is related to the basal level of endogenous phosphorylated Akt. We further demonstrate that nonpermissive tumor cells will switch from resistant to susceptible for MV infection after expression of ectopically active Akt (Myr-Akt) and that permissive cancer cells can be rendered nonpermissive by blocking Akt activation with a dominant-negative inhibitor of Akt. Finally, the activation of Akt by MV involves the formation of a complex between the viral host range ankyrin-repeat protein, M-T5, and Akt. We conclude that the Akt pathway is a key restriction determinant for permissiveness of human cancer cells by MV.

  14. Analysis of rotavirus antigenemia and extraintestinal manifestations in children with rotavirus gastroenteritis.

    Science.gov (United States)

    Sugata, Ken; Taniguchi, Koki; Yui, Akiko; Miyake, Fumi; Suga, Sadao; Asano, Yoshizo; Ohashi, Masahiro; Suzuki, Kyoko; Nishimura, Naoko; Ozaki, Takao; Yoshikawa, Tetsushi

    2008-08-01

    This study was conducted to examine the association between rotavirus antigenemia and clinical features, particularly extraintestinal manifestations, and the association between serum cytokine levels and rotavirus antigen quantity. Sixty hospitalized children who received a diagnosis of acute rotavirus gastroenteritis were enrolled in this study. Paired serum samples were collected from the 60 children when admitted to and discharged from the hospital. Associations among viral antigen levels and fever, elevated transaminase levels, and seizures were evaluated to determine whether antigenemia correlated with disease severity. Viral antigen was measured by using an in-house enzyme-linked immunosorbent assay that detected VP6 antigen. A flow-cytometric bead array was used to measure serum cytokine levels. Rotavirus antigen levels were significantly higher in serum collected at the time of hospital admission than at the time of discharge. Serum rotavirus antigen levels peaked on day 2 of the illness (2.02 +/- 0.73), followed by a gradual decrease in antigen levels to nearly undetectable levels by day 6. The quantity of rotavirus antigen was significantly higher in serum collected from patients with fever than those without fever. The presence or absence of elevated transaminase levels and seizures was not associated with serum rotavirus antigen levels. A weak but significantly positive association was observed between interleukin 8 levels and antigenemia. A weak but significantly negative association was observed between interleukin 10 levels and antigenemia. Rotavirus antigenemia is frequently observed in a patient's serum during the acute phase, and viral antigen levels change dramatically during the acute phase of the illness. Because patients with fever had higher rotavirus antigen levels, antigenemia severity might contribute to fever. The host immune response plays an important role in controlling antigenemia levels.

  15. Remyelination Is Correlated with Regulatory T Cell Induction Following Human Embryoid Body-Derived Neural Precursor Cell Transplantation in a Viral Model of Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Warren C Plaisted

    Full Text Available We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs derived from human embryonic stem cells (hESCs in a viral model of the human demyelinating disease multiple sclerosis. The hNPCs used in that study were derived by a novel direct differentiation method (direct differentiation, DD-NPCs that resulted in a unique gene expression pattern when compared to hNPCs derived by conventional methods. Since the therapeutic potential of human NPCs may differ greatly depending on the method of derivation and culture, we wanted to determine whether NPCs differentiated using conventional methods would be similarly effective in improving clinical outcome under neuroinflammatory demyelinating conditions. For the current study, we utilized hNPCs differentiated from a human induced pluripotent cell line via an embryoid body intermediate stage (EB-NPCs. Intraspinal transplantation of EB-NPCs into mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV resulted in decreased accumulation of CD4+ T cells in the central nervous system that was concomitant with reduced demyelination at the site of injection. Dampened neuroinflammation and remyelination was correlated with a transient increase in CD4+FOXP3+ regulatory T cells (Tregs concentrated within the peripheral lymphatics. However, compared to our earlier study, pathological improvements were modest and did not result in significant clinical recovery. We conclude that the genetic signature of NPCs is critical to their effectiveness in this model of viral-induced neurologic disease. These comparisons will be useful for understanding what factors are critical for the sustained clinical improvement.

  16. Expression of E6/E7 mRNA from 'high risk' human papillomavirus in relation to CIN grade, viral load and p16INK4a.

    Science.gov (United States)

    Andersson, Sonia; Hansson, Berit; Norman, Ingrid; Gaberi, Vera; Mints, Miriam; Hjerpe, Anders; Karlsen, Frank; Johansson, Bo

    2006-09-01

    Detection of E6/E7 mRNA expression with real-time nucleic acid sequence-based amplification assay (NASBA) method (PreTect HPV-Proofer) from high-risk types of human papillomaviruses (HR-HPV) were compared with the presence of viral load, determined with quantitative real-time PCR in 80 cervical samples. Results regarding positivity and typing were in agreement using the two methods. However, there was no correlation between viral loads for HPV 16 or 18/45 and oncogene expression. Among 15 women with low grade atypia detected at a population-based cytology screening, and scored as 'within normal limits' according to histopathology, 14% were positive for oncogene expression, whereas 71% were HR-HPV positive. A correlation was observed between HR-HPV oncogene expression and high scores of p16(INK4a) positivity. Since HPV-Proofer detects full-length E6/E7 mRNA, a positive result should correlate with presence of integrated HPV, loss of HPV replication and stabilized E6/E7 full-length mRNA expression. Such expression from integrated HR-HPV generates a high and stable expression of full-length E6 proteins, which explains why a positive HPV-Proofer result was independent of viral load and correlate with high expression of p16(INK4a). Thus, E6/E7 oncogene expression analysis yielded information, which is consistent with and will complement the results from a real-time PCR method in a clinical prognostic procedure.

  17. Up-regulation of Mcl-1 and Bak by coronavirus infection of human, avian and animal cells modulates apoptosis and viral replication.

    Directory of Open Access Journals (Sweden)

    Yanxin Zhong

    Full Text Available Virus-induced apoptosis and viral mechanisms that regulate this cell death program are key issues in understanding virus-host interactions and viral pathogenesis. Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expression profiles are first determined in IBV-infected Vero cells at 24 hours post-infection by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV as a model system. It reveals an up-regulation at the transcriptional level of both pro-apoptotic Bak and pro-survival myeloid cell leukemia-1 (Mcl-1. These results were further confirmed both in vivo and in vitro, in IBV-infected embryonated chicken eggs, chicken fibroblast cells and mammalian cells at transcriptional and translational levels, respectively. Interestingly, the onset of apoptosis occurred earlier in IBV-infected mammalian cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1, and was delayed in cells silenced with siBak. IBV progeny production and release were increased in infected Mcl-1 knockdown cells compared to similarly infected control cells, while the contrary was observed in infected Bak knockdown cells. Furthermore, IBV infection-induced up-regulation of GADD153 regulated the expression of Mcl-1. Inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK and phosphoinositide 3-kinase (PI3K/Akt signaling pathways by chemical inhibitors and knockdown of GADD153 by siRNA demonstrated the involvement of ER-stress response in regulation of IBV-induced Mcl-1 expression. These results illustrate the sophisticated regulatory strategies evolved by a coronavirus to modulate both virus-induced apoptosis and viral replication during its replication cycle.

  18. Up-regulation of Mcl-1 and Bak by coronavirus infection of human, avian and animal cells modulates apoptosis and viral replication.

    Science.gov (United States)

    Zhong, Yanxin; Liao, Ying; Fang, Shouguo; Tam, James P; Liu, Ding Xiang

    2012-01-01

    Virus-induced apoptosis and viral mechanisms that regulate this cell death program are key issues in understanding virus-host interactions and viral pathogenesis. Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expression profiles are first determined in IBV-infected Vero cells at 24 hours post-infection by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV) as a model system. It reveals an up-regulation at the transcriptional level of both pro-apoptotic Bak and pro-survival myeloid cell leukemia-1 (Mcl-1). These results were further confirmed both in vivo and in vitro, in IBV-infected embryonated chicken eggs, chicken fibroblast cells and mammalian cells at transcriptional and translational levels, respectively. Interestingly, the onset of apoptosis occurred earlier in IBV-infected mammalian cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1), and was delayed in cells silenced with siBak. IBV progeny production and release were increased in infected Mcl-1 knockdown cells compared to similarly infected control cells, while the contrary was observed in infected Bak knockdown cells. Furthermore, IBV infection-induced up-regulation of GADD153 regulated the expression of Mcl-1. Inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) and phosphoinositide 3-kinase (PI3K/Akt) signaling pathways by chemical inhibitors and knockdown of GADD153 by siRNA demonstrated the involvement of ER-stress response in regulation of IBV-induced Mcl-1 expression. These results illustrate the sophisticated regulatory strategies evolved by a coronavirus to modulate both virus-induced apoptosis and viral replication during its replication cycle.

  19. Multicenter evaluation of the BioFire FilmArray gastrointestinal panel for etiologic diagnosis of infectious gastroenteritis.

    Science.gov (United States)

    Buss, Sarah N; Leber, Amy; Chapin, Kimberle; Fey, Paul D; Bankowski, Matthew J; Jones, Matthew K; Rogatcheva, Margarita; Kanack, Kristen J; Bourzac, Kevin M

    2015-03-01

    The appropriate treatment and control of infectious gastroenteritis depend on the ability to rapidly detect the wide range of etiologic agents associated with the disease. Clinical laboratories currently utilize an array of different methodologies to test for bacterial, parasitic, and viral causes of gastroenteritis, a strategy that suffers from poor sensitivity, potentially long turnaround times, and complicated ordering practices and workflows. Additionally, there are limited or no testing methods routinely available for most diarrheagenic Escherichia coli strains, astroviruses, and sapoviruses. This study assessed the performance of the FilmArray Gastrointestinal (GI) Panel for the simultaneous detection of 22 different enteric pathogens directly from stool specimens: Campylobacter spp., Clostridium difficile (toxin A/B), Plesiomonas shigelloides, Salmonella spp., Vibrio spp., Vibrio cholerae, Yersinia enterocolitica, enteroaggregative E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, Shiga-like toxin-producing E. coli (stx1 and stx2) (including specific detection of E. coli O157), Shigella spp./enteroinvasive E. coli, Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica, Giardia lamblia, adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A, and sapovirus. Prospectively collected stool specimens (n = 1,556) were evaluated using the BioFire FilmArray GI Panel and tested with conventional stool culture and molecular methods for comparison. The FilmArray GI Panel sensitivity was 100% for 12/22 targets and ≥94.5% for an additional 7/22 targets. For the remaining three targets, sensitivity could not be calculated due to the low prevalences in this study. The FilmArray GI Panel specificity was ≥97.1% for all panel targets. The FilmArray GI Panel provides a comprehensive, rapid, and streamlined alternative to conventional methods for the etiologic diagnosis of infectious gastroenteritis in the laboratory setting. The potential

  20. Human Cytomegalovirus-Encoded Receptor US28 Is Expressed in Renal Allografts and Facilitates Viral Spreading In Vitro

    NARCIS (Netherlands)

    Lollinga, Wouter T; de Wit, Raymond H; Rahbar, Afsar; Vasse, Gwenda F; Davoudi, Belghis; Diepstra, Arjan; Riezebos-Brilman, Annelies; Harmsen, Martin C; Hillebrands, Jan-Luuk; Söderberg-Naucler, Cecilia; van Son, Willem J; Smit, Martine J; Sanders, Jan-Stephan; van den Born, Jacob

    BACKGROUND: Renal transplantation is the preferred treatment for patients with end-stage renal disease. Human cytomegalovirus (HCMV) activation is associated with decreased renal graft function and survival. Human cytomegalovirus encodes several immune modulatory proteins, including the G

  1. SAPOVIRUSES IN CHILDREN WITH ACUTE GASTROENTERITIS FROM MANAUS , AMAZON REGION, BRAZIL, 2010-2011.

    Science.gov (United States)

    Reymão, Tammy Kathlyn Amaral; Hernandez, Juliana das Merces; Costa, Samya Thalita Picanço da; Sousa, Maísa Silva de; Oliveira, Darleise de Souza; Silva, Luciana Damascena da; Bandeira, Renato da Silva; Lima, Ian Carlos Gomes de; Soares, Luana da Silva; Mascarenhas, Joana Darc Pereira; Gabbay, Yvone Benchimol

    2016-11-03

    Sapoviruses (SaVs) are responsible for acute gastroenteritis in humans, especially children and the elderly. In Brazil, data on SaVs infections are very limited, especially in Northern Brazil. Here, we investigated the occurrence of SaVs in samples from hospitalized children under ten years old that presented acute gastroenteritis. Positive samples were genotyped and phylogenetic analysis was performed using prototype strains sequences obtained from GenBank database. In total, 156 fecal samples were screened by RT-PCR for SaVs. A positivity rate of 3.8% (6/156) was found in children under three years of age. Four genotypes were detected: GI.I, GI.2 and GII.2?-GII.4?/GII.4, suggesting a possible inter-genotypes recombination. Most infections (83.3%) occurred between August and September. The positivity was similar to that found in other countries and genotyping demonstrated the presence of distinct genotypes. To our knowledge, this is the first study reporting the circulation of SaVs in Manaus, state of Amazonas, Amazon region, Brazil.

  2. MANAGEMENT OF ACUTE GASTROENTERITIS IN CHILDREN: WHAT IS NEW?

    Directory of Open Access Journals (Sweden)

    I. N. Zakharova

    2013-01-01

    Full Text Available High prevalence of acute enteric infections in children, the majority of which affects infants, determines the necessity of development of modern recommendation on diagnostics and treatment of such conditions. The authors show data on etiology of enteric infections and results of various Russian and international research on efficacy of treatment of acute gastroenteritis, including information about sorbents, probiotics, antiemetic agents and antibacterial drugs usage. Recommendations on treatment of acute gastroenteritis are based on the modern protocol of the European Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists (ESPGHAN, which was published in 2008. According to these recommendations, oral rehydration is one of the main components of treatment, decreasing children’s mortality rates. However due to the absence of the effect of this measure on the intestinal peristalsis, duration of the diarrhea and concomitant symptoms (abdominal pain and distension, additional therapy is necessary. In Russia combinations of enterosorbents and probiotics are used in order to relieve such conditions.

  3. An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock.

    Science.gov (United States)

    Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P

    2015-01-01

    Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration.

  4. An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock

    Directory of Open Access Journals (Sweden)

    Miguel Martillo

    2015-05-01

    Full Text Available Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration.

  5. Eosinophilic Gastroenteritis Presenting as Intestinal Obstruction - A Case Series

    Directory of Open Access Journals (Sweden)

    Amita Krishnappa

    2011-07-01

    Full Text Available Eosinophilic Gastroenteritis is a rare disease characterized by infiltration of the gastrointestinal tract by an increased number of eosinophils as compared to the normal. The anatomic location and intensity of the infiltrate decides the varied clinical symptomatology with which these patients present. The present report deals with four cases, all presenting with clinical signs of intestinal obstruction A laparotomy performed revealed a stricture in the first case, superficial ulcers and adhesions in the second case, an ileocaecal mass in the third case and volvulus formation in the fourth case. Eosinophilic gastroenteritis was confirmed on histopathology in all the four cases. All the four patients experienced relief of symptoms after resection. It is essential to diagnose the disease to differentiate it from other conditions presenting as intestinal obstruction. The cases are presented because of the rarity of occurrence and presentation. Relevant literature has been reviewed.

  6. Recent Progress in the Research of Eosinophilic Esophagitis and Gastroenteritis.

    Science.gov (United States)

    Kinoshita, Yoshikazu; Ishimura, Norihisa; Oshima, Naoki; Mikami, Hironobu; Okimoto, Eiko; Jiao, Di Jin; Ishihara, Shunji

    2016-01-01

    Eosinophilic esophagitis (EoE) and gastroenteritis are allergic gastrointestinal diseases mainly caused by food allergens. The number of patients with EoE is rapidly increasing in both Western and Asian countries. Basic knowledge of these diseases has mainly come from studies of EoE and Th2 type allergic reactions, including IL-5, IL-13, and IL-15, thymic stromal protein, and eotaxin 3, which are considered to have important roles. For a diagnosis of EoE, endoscopic abnormalities and histological confirmation of dense eosinophile infiltration in the esophageal epithelial layer are important, in addition to identifying dysphagia symptoms. As for eosinophilic gastroenteritis, blood test findings are more useful and the role of an endoscopic examination is reduced. For both diseases, the infection rate of Helicobacter pylori is lower than in healthy controls. Glucocorticoid administration is standard treatment for these diseases, while proton pump inhibitors are frequently effective for EoE. © 2016 S. Karger AG, Basel.

  7. Staphylococcus aureus endocarditis and pyomyositis: Rare complications of rotavirus gastroenteritis.

    Science.gov (United States)

    Aldemir-Kocabaş, Bilge; Karbuz, Adem; Kara, Tuğçe Tural; Çiftçi, Ömer; Uçar, Tayfun; Fitöz, Suat; Çiftçi, Ergin; İnce, Erdal

    2015-08-01

    Rotavirus may cause life-threatening complications in untreated patients during the course of gastroenteritis. Electrolyte imbalance, bacteremia and sepsis are the most common complications of rotavirus gastroenteritis (RG). It is believed that translocation of intestinal microorganisms as a result of intestinal epithelium dysfunction is the underlying mechanism of bacteremia in RG. Although Gram-negative bacteremia has been noted as a complication in RG, Staphylococcus aureus bacteremia and endocarditis have not been reported previously. A 22-month-old boy was admitted with complaints of fever, diarrhea and dehydration. He was diagnosed with RG complicated with S. aureus bacteremia, pyomyositis and endocarditis. We call attention to these complications in patients with prolonged or late-onset fever during RG as rare complications of the disease. © 2015 Japan Pediatric Society.

  8. Direct and Indirect Costs of Pediatric Gastroenteritis in Vellore, India.

    Science.gov (United States)

    Jacob, Joby; Joseph, Tej K; Srinivasan, Rajan; Kompithra, Rajeev Zachariah; Simon, Anna; Kang, Gagandeep

    2016-07-08

    To determine costs of pediatric gastroenteritis in out-patient and in-patient facilities. Cross-sectional survey of children with acute gastroenteritis attending out-patient clinic (n=30) or admitted in the ward (n=30) for management in the Christian Medical College, Vellore, India from July-September 2014 to estimate direct (drugs, tests, consultation/hospitalization) and indirect (travel, food, lost wages) costs associated with the episode. Median direct and indirect costs were Rs 590 and Rs 190 for out-patient management and Rs 7258 and Rs. 610 for hospitalization, constituting 1.1% and 11% of median annual household income, respectively. Escalating healthcare costs need tracking for evaluation of interventions.

  9. An Electrostatically Self-Assembled Ternary Nanocomplex as a Non-Viral Vector for the Delivery of Plasmid DNA into Human Adipose-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Sun-Hee Cho

    2016-04-01

    Full Text Available In this study, we developed electrostatically self-assembled ternary nanocomplexes as a safe and effective non-viral vector for the delivery of plasmid DNA (pDNA into human adipose-derived stem cells (hASCs. Although polyethylenimine (PEI polymers initially showed excellent performance as gene delivery carriers, their broad use has been limited by cytotoxicity resulting from their strong positive charge. To reduce the cytotoxicity, we utilized anionic hyaluronic acid (HA as a corona layer material for pDNA/PEI binary nanocomplexes. HA was also introduced to increase the targeting efficiency of pDNA/PEI nanocomplexes because HA has can bind CD44 that is highly expressed on the surface of hASCs. We confirmed that the addition of HA changed the surface charge of pDNA/PEI nanocomplexes from positive to negative. The pDNA/PEI/HA ternary nanocomplexes showed high transfection efficiency and low cytotoxicity compared with commercially available products. When hASCs were pretreated with HA to passivate CD44, the transfection efficiency of pDNA/PEI/HA nanocomplexes was significantly reduced. These results suggest that HA that can act as a targeting ligand to CD44 contributed to the improved transfection of pDNA into hASCs. Our novel pDNA/PEI/HA nanocomplexes may be used as an effective non-viral pDNA delivery system for hASCs.

  10. Protective efficacy of VP1-specific neutralizing antibody associated with a reduction of viral load and pro-inflammatory cytokines in human SCARB2-transgenic mice.

    Science.gov (United States)

    Chang, Hsuen-Wen; Lin, Yi-Wen; Ho, Hui-Min; Lin, Min-Han; Liu, Chia-Chyi; Shao, Hsiao-Yun; Chong, Pele; Sia, Charles; Chow, Yen-Hung

    2013-01-01

    Hand-foot-mouth diseases (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16) as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype) or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype). This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.

  11. Human papillomavirus and head and neck squamous cell carcinomas in the South-East of France: prevalence, viral expression, and prognostic implications.

    Science.gov (United States)

    Gavid, Marie; Pillet, Sylvie; Pozzetto, Bruno; Oriol, Mathieu; Dumollard, Jean-Marc; Timoshenko, Andrei P; Martin, Christian; Prades, Jean-Michel

    2013-05-01

    Human papillomavirus (HPV) infection, especially by HPV 16, is frequently detected in oropharyngeal squamous cell carcinoma (OSCC). The expression of viral oncoproteins in tumoral tissues of OSCCs suggests the implication of HPV in tumorogenesis. It should now be systematically detected and considered in each patient's treatment and outcome. To investigate the prevalence of HPV infection, the oncogenic role of HPV in patients from the South-East of France with head and neck squamous cell carcinoma (HNSCC), and the resulting clinical implications. Biopsy samples from 200 patients with HNSCC were analyzed. For each patient, one or two biopsies of tumoral tissue were analyzed simultaneously with a biopsy of healthy tissue. Fresh frozen tissues were tested by molecular techniques for HPV DNA detection and genotyping as well as mRNA expression of oncoproteins E6 and E7. Expression of p16 was also analyzed by immunohistochemical staining. HPV DNA tested positive in 11.5% of biopsy samples. The HPV prevalence was higher in OSCCs (91.3 vs 27.3, p 16 was the most common type detected (65.2%). In 12 of 18 patients exhibiting DNA of high-risk HPV in their tumor tissue, the same viral genome was also present in normal tissue. E6 and E7 expression was found in 9 of 14 tumoral biopsies tested for these markers.

  12. Introduction of Exogenous Epitopes in the Variable Regions of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein: Effect on Viral Infectivity and the Neutralization Phenotype▿

    Science.gov (United States)

    Wallace, Aaron; Stamatatos, Leonidas

    2009-01-01

    In this study we examined whether human immunodeficiency virus type 1 (HIV-1) is equally susceptible to neutralization by a given antibody when the epitope of this antibody is introduced at different positions within the viral envelope glycoprotein (Env). To this end, we introduced two exogenous “epitope tags” at different locations within three major Env regions in two distinct HIV-1 isolates. We examined how the introduction of the exogenous epitopes affects Env expression, Env incorporation into virions, Env fusogenic potential, and viral susceptibility to neutralization. Our data indicate that even within the same Env region, the exact positioning of the epitope impacts the susceptibility of the virus to neutralization by the antibody that binds to that epitope. Our data also indicate that even if the same epitope is introduced in the exact same position on two different Envs, its exposure and, as a result, the neutralization susceptibility of the virus, can be very different. In contrast to the findings of previous studies conducted with HIV-1 isolates other than those used here, but in agreement with results obtained with simian immunodeficiency virus, we observed that tagging of the fourth variable region of Env (V4) did not result in neutralization by the anti-tag antibodies. Our data indicate that epitopes in V4 are not properly exposed within the functional HIV-1 trimeric Env spike, suggesting that V4 may not be a good target for vaccine-elicited neutralizing antibodies. PMID:19494007

  13. Introduction of exogenous epitopes in the variable regions of the human immunodeficiency virus type 1 envelope glycoprotein: effect on viral infectivity and the neutralization phenotype.

    Science.gov (United States)

    Wallace, Aaron; Stamatatos, Leonidas

    2009-08-01

    In this study we examined whether human immunodeficiency virus type 1 (HIV-1) is equally susceptible to neutralization by a given antibody when the epitope of this antibody is introduced at different positions within the viral envelope glycoprotein (Env). To this end, we introduced two exogenous "epitope tags" at different locations within three major Env regions in two distinct HIV-1 isolates. We examined how the introduction of the exogenous epitopes affects Env expression, Env incorporation into virions, Env fusogenic potential, and viral susceptibility to neutralization. Our data indicate that even within the same Env region, the exact positioning of the epitope impacts the susceptibility of the virus to neutralization by the antibody that binds to that epitope. Our data also indicate that even if the same epitope is introduced in the exact same position on two different Envs, its exposure and, as a result, the neutralization susceptibility of the virus, can be very different. In contrast to the findings of previous studies conducted with HIV-1 isolates other than those used here, but in agreement with results obtained with simian immunodeficiency virus, we observed that tagging of the fourth variable region of Env (V4) did not result in neutralization by the anti-tag antibodies. Our data indicate that epitopes in V4 are not properly exposed within the functional HIV-1 trimeric Env spike, suggesting that V4 may not be a good target for vaccine-elicited neutralizing antibodies.

  14. Immunization with a Mixture of Nucleoprotein from Human Metapneumovirus and AbISCO-100 Adjuvant Reduces Viral Infection in Mice Model.

    Science.gov (United States)

    Diaz-Dinamarca, Diego A; Ibañez, Francisco J; Soto, Daniel A; Soto, Jorge A; Cespedes, Pablo F; Muena, Nicolás A; Garate, Diego S; Kalergis, Alexis M; Vasquez, Abel E

    2018-01-26

    The human metapneumovirus (hMPV) is the second leading cause globally of acute infection of the respiratory tract in children, infecting the upper and lower airways. The hMPV may induce an inappropriate Th2-type immune response, which causes severe pulmonary inflammation, leading to the obstruction of airways. Despite its severe epidemiological relevance, no vaccines are currently available for the prevention of hMPV-induced illness. In this investigation, we demonstrated that immunization of mice with the recombinant hMPV nucleoprotein (hMPV-N) mixed with the AbISCO-100 adjuvant reduced viral replication in lungs following challenge with the virus. We found that immunized mice had reduced weight loss, decreased granulocytes in the lung, an increased level of specific nucleoprotein antibodies of IgG1 and IgG2a-isotypes, and a local profile of Th1/Th17-type cytokines. Our results suggest that immunization with the hMPV-N and the AbISCO-100 adjuvant induces a reduction of viral infection and could be considered for the development of an hMPV vaccine.

  15. Protective efficacy of VP1-specific neutralizing antibody associated with a reduction of viral load and pro-inflammatory cytokines in human SCARB2-transgenic mice.

    Directory of Open Access Journals (Sweden)

    Hsuen-Wen Chang

    Full Text Available Hand-foot-mouth diseases (HFMD caused by enterovirus 71 (EV71 and coxsackievirus 16 (CVA16 in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16 as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype. This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.

  16. Type-dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18.

    Science.gov (United States)

    Fu Xi, Long; Schiffman, Mark; Ke, Yang; Hughes, James P; Galloway, Denise A; He, Zhonghu; Hulbert, Ayaka; Winer, Rachel L; Koutsky, Laura A; Kiviat, Nancy B

    2017-04-15

    Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non-HPV16/18 oncogenic types detected during a 2-year follow-up at 6-month intervals. Viral load measurements were performed on the first type-specific HPV-positive specimens. The association of cervical intraepithelial neoplasia grades 2-3 (CIN2/3) with type-specific HPV DNA load was assessed with discrete-time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log 10 -transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR adjusted ] = 1.32: 95% confidence interval [CI], 1.14-1.52), HPV35 (HR adjusted  = 1.47; 95% CI, 1.23-1.76), HPV52 (HR adjusted  = 1.14; 95% CI, 1.01-1.30) and HPV58 (HR adjusted  = 1.49; 95% CI, 1.23-1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log 10 -unit increase in viral load of a group of species 9 non-HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC-US, or LSIL at the first HPV-positive visit but not for those with high-grade SIL. Findings suggest that the viral load-associated risk of CIN2/3 is type-dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association. © 2017 UICC.

  17. Source and Purity of Dengue-Viral Preparations Impact Requirement for Enhancing Antibody to Induce Elevated IL-1β Secretion: A Primary Human Monocyte Model.

    Science.gov (United States)

    Callaway, Justin B; Smith, Scott A; Widman, Douglas G; McKinnon, Karen P; Scholle, Frank; Sempowski, Gregory D; Dittmer, Dirk P; Crowe, James E; de Silva, Aravinda M; Ting, Jenny P-Y

    2015-01-01

    Dengue virus is a major global health threat and can lead to life-threatening hemorrhagic complications due to immune activation and cytokine production. Cross-reactive antibodies to an earlier dengue virus infection are a recognized risk factor for severe disease. These antibodies bind heterologous dengue serotypes and enhance infection into Fc-receptor-bearing cells, a process known as antibody-dependent enhancement of infection. One crucial cytokine seen elevated in severe dengue patients is IL-1β, a potent inflammatory cytokine matured by the inflammasome. We used a highly-physiologic system by studying antibody-dependent enhancement of IL-1β in primary human monocytes with anti-dengue human monoclonal antibodies isolated from patients. Antibody-enhancement increased viral replication in primary human monocytes inoculated with supernatant harvested from Vero cells infected with dengue virus serotype 2 (DENV-2) 16681. Surprisingly, IL-1β secretion induced by infectious supernatant harvested from two independent Vero cell lines was not enhanced by antibody. Secretion of multiple other inflammatory cytokines was also independent of antibody signaling. However, IL-1β secretion did require NLRP3 and caspase-1 activity. Immunodepletion of dengue virions from the infectious supernatant confirmed that virus was not the main IL-1β-inducing agent, suggesting that a supernatant component(s) not associated with the virion induced IL-1β production. We excluded RNA, DNA, contaminating LPS, viral NS1 protein, complement, and cytokines. In contrast, purified Vero-derived DENV-2 16681 exhibited antibody-enhancement of both infection and IL-1β induction. Furthermore, C6/36 mosquito cells did not produce such an inflammatory component, as crude supernatant harvested from insect cells infected with DENV-2 16681 induced antibody-dependent IL-1β secretion. This study indicates that Vero cells infected with DENV-2 16681 may produce inflammatory components during dengue virus

  18. Source and Purity of Dengue-Viral Preparations Impact Requirement for Enhancing Antibody to Induce Elevated IL-1β Secretion: A Primary Human Monocyte Model.

    Directory of Open Access Journals (Sweden)

    Justin B Callaway

    Full Text Available Dengue virus is a major global health threat and can lead to life-threatening hemorrhagic complications due to immune activation and cytokine production. Cross-reactive antibodies to an earlier dengue virus infection are a recognized risk factor for severe disease. These antibodies bind heterologous dengue serotypes and enhance infection into Fc-receptor-bearing cells, a process known as antibody-dependent enhancement of infection. One crucial cytokine seen elevated in severe dengue patients is IL-1β, a potent inflammatory cytokine matured by the inflammasome. We used a highly-physiologic system by studying antibody-dependent enhancement of IL-1β in primary human monocytes with anti-dengue human monoclonal antibodies isolated from patients. Antibody-enhancement increased viral replication in primary human monocytes inoculated with supernatant harvested from Vero cells infected with dengue virus serotype 2 (DENV-2 16681. Surprisingly, IL-1β secretion induced by infectious supernatant harvested from two independent Vero cell lines was not enhanced by antibody. Secretion of multiple other inflammatory cytokines was also independent of antibody signaling. However, IL-1β secretion did require NLRP3 and caspase-1 activity. Immunodepletion of dengue virions from the infectious supernatant confirmed that virus was not the main IL-1β-inducing agent, suggesting that a supernatant component(s not associated with the virion induced IL-1β production. We excluded RNA, DNA, contaminating LPS, viral NS1 protein, complement, and cytokines. In contrast, purified Vero-derived DENV-2 16681 exhibited antibody-enhancement of both infection and IL-1β induction. Furthermore, C6/36 mosquito cells did not produce such an inflammatory component, as crude supernatant harvested from insect cells infected with DENV-2 16681 induced antibody-dependent IL-1β secretion. This study indicates that Vero cells infected with DENV-2 16681 may produce inflammatory components

  19. Eosinophilic Gastroenteritis as a Rare Cause of Recurrent Epigastric Pain

    Directory of Open Access Journals (Sweden)

    Mohammad Taghi Safari

    2016-04-01

    Full Text Available Eosinophilic gastroenteritis (EGE is a rare inflammatory disorder of gastrointestinal tract characterized by eosinophilic infiltration of the bowel wall. It can mimic many gastrointestinal disorders due to its wide spectrum of presentations. Diagnose is mostly based on excluding other disorders and a high suspicion. Here we report a case of 26 year old man with a history of sever epigastric pain followed by nausea, vomiting since a few days before admission with final diagnosis of EGE.

  20. Eosinophilic Gastroenteritis as a Rare Cause of Recurrent Epigastric Pain

    Science.gov (United States)

    Safari, Mohammad Taghi; Shahrokh, Shabnam; Miri, Mohammad Bagher; Ehsani Ardakani, Mohammad Javad

    2016-01-01

    Eosinophilic gastroenteritis (EGE) is a rare inflammatory disorder of gastrointestinal tract characterized by eosinophilic infiltration of the bowel wall. It can mimic many gastrointestinal disorders due to its wide spectrum of presentations. Diagnose is mostly based on excluding other disorders and a high suspicion. Here we report a case of 26 year old man with a history of sever epigastric pain followed by nausea, vomiting since a few days before admission with final diagnosis of EGE. PMID:27274524

  1. Unexpectedly high burden of rotavirus gastroenteritis in very young infants

    Directory of Open Access Journals (Sweden)

    Reilly Megan

    2010-06-01

    Full Text Available Abstract Background The highest incidence of rotavirus gastroenteritis has generally been reported in children 6-24 months of age. Young infants are thought to be partially protected by maternal antibodies acquired transplacentally or via breast milk. The purpose of our study was to assess the age distribution of children with confirmed community-acquired rotavirus gastroenteritis presenting to an urban referral hospital. Methods Children presenting to The Children's Hospital of Philadelphia with acute gastroenteritis have been monitored for the presence of rotavirus antigen in the stool by ELISA (followed by genotyping if ELISA-positive since the 1994-95 epidemic season. Results Over the last 12 rotavirus seasons prior to the introduction of the pentavalent rotavirus vaccine in 2006, stool specimens from 1646 patients tested positive for community-acquired rotavirus infection. Gender or age was not recorded in 6 and 5 cases, respectively. Overall, 58% of the cases occurred in boys. G1 was the predominant VP7 serotype, accounting for 72% of cases. The median (IQR age was 11 (5-21 months. A total of 790 (48% cases occurred in children outside the commonly quoted peak age range, with 27% in infants 24 months of age. A total of 220 (13% cases occurred during the first 3 months of life, and the highest number of episodes per month of age [97 (6%] was observed during the second month of life. Conclusions The incidence of community-acquired rotavirus gastroenteritis monitored over 12 seasons in the prevaccine era at a major university hospital was nearly constant for each month of age during the first year of life, revealing an unexpectedly high incidence of symptomatic rotavirus disease in infants

  2. Multiplex PCR Tests for Detection of Pathogens Associated with Gastroenteritis

    OpenAIRE

    Zhang, Hongwei; Morrison, Scott; Tang, Yi-Wei

    2015-01-01

    A wide range of enteric pathogens can cause infectious gastroenteritis. Conventional diagnostic algorithms including culture, biochemical identification, immunoassay and microscopic examination are time consuming and often lack sensitivity and specificity. Advances in molecular technology have as allowed its use as clinical diagnostic tools. Multiplex PCR based testing has made its way to gastroenterology diagnostic arena in recent years. In this article we present a review of recent laborato...

  3. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome.

    Science.gov (United States)

    Chen, Yu; Liang, Weifeng; Yang, Shigui; Wu, Nanping; Gao, Hainv; Sheng, Jifang; Yao, Hangping; Wo, Jianer; Fang, Qiang; Cui, Dawei; Li, Yongcheng; Yao, Xing; Zhang, Yuntao; Wu, Haibo; Zheng, Shufa; Diao, Hongyan; Xia, Shichang; Zhang, Yanjun; Chan, Kwok-Hung; Tsoi, Hoi-Wah; Teng, Jade Lee-Lee; Song, Wenjun; Wang, Pui; Lau, Siu-Ying; Zheng, Min; Chan, Jasper Fuk-Woo; To, Kelvin Kai-Wang; Chen, Honglin; Li, Lanjuan; Yuen, Kwok-Yung

    2013-06-01

    Human infection with avian influenza A H7N9 virus emerged in eastern China in February, 2013, and has been associated with exposure to poultry. We report the clinical and microbiological features of patients infected with influenza A H7N9 virus and compare genomic features of the human virus with those of the virus in market poultry in Zhejiang, China. Between March 7 and April 8, 2013, we included hospital inpatients if they had new-onset respiratory symptoms, unexplained radiographic infiltrate, and laboratory-confirmed H7N9 virus infection. We recorded histories and results of haematological, biochemical, radiological, and microbiological investigations. We took throat and sputum samples, used RT-PCR to detect M, H7, and N9 genes, and cultured samples in Madin-Darby canine kidney cells. We tested for co-infections and monitored serum concentrations of six cytokines and chemokines. We collected cloacal swabs from 86 birds from epidemiologically linked wet markets and inoculated embryonated chicken eggs with the samples. We identified and subtyped isolates by RT-PCR sequencing. RNA extraction, complementary DNA synthesis, and PCR sequencing were done for one human and one chicken isolate. We characterised and phylogenetically analysed the eight gene segments of the viruses in the patient's and the chicken's isolates, and constructed phylogenetic trees of H, N, PB2, and NS genes. We identified four patients (mean age 56 years), all of whom had contact with poultry 3-8 days before disease onset. They presented with fever and rapidly progressive pneumonia that did not respond to antibiotics. Patients were leucopenic and lymphopenic, and had impaired liver or renal function, substantially increased serum cytokine or chemokine concentrations, and disseminated intravascular coagulation with disease progression. Two patients died. Sputum specimens were more likely to test positive for the H7N9 virus than were samples from throat swabs. The viral isolate from the patient

  4. Viral arthritis

    Science.gov (United States)

    ... any lasting effects. It may occur with: Enterovirus Dengue virus Hepatitis B Hepatitis C Human immunodeficiency virus ( ... joint to determine the cause of the inflammation. Treatment Your health care provider may prescribe pain medicines ...

  5. Three gastroenteritis outbreaks in South Korea caused by the consumption of kimchi tainted by norovirus GI.4.

    Science.gov (United States)

    Park, Ji-Hyuk; Jung, Sunyoung; Shin, Jaeseung; Lee, Jeong Su; Joo, In Sun; Lee, Deog-Yong

    2015-03-01

    In April 2013, outbreaks of acute gastroenteritis were reported at three schools in Jeonju, South Korea. Epidemiological investigations were performed to characterize the outbreaks and implement appropriate control measures. Retrospective cohort studies were performed at these schools. Stool and environmental samples were collected for bacterial and viral assessment. A food supplier of the schools, food company X, was inspected, and samples of cabbage kimchi and groundwater were tested for norovirus by real-time reverse-transcriptase polymerase chain reaction. The relatedness of the detected norovirus strains was evaluated by phylogenetic analysis. Of the 3347 questionnaires distributed, 631 (attack rate: 18.9%) met the case definition. Among the consumed food items, kimchi products (i.e., cabbage and fresh kimchi) were significantly associated with illness. The kimchi products were supplied by food company X. Among stool samples from 95 students and 34 food handlers at the 3 schools, 39 (41.1%) and 14 (41.2%) samples, respectively, were positive for norovirus. The samples of groundwater and cabbage kimchi at food company X were positive for norovirus. The predominant genotype of norovirus detected in the patient, groundwater, and cabbage kimchi samples, GI.4, shared high nucleotide identity. Kimchi products tainted with norovirus GI.4 from contaminated groundwater were linked to the acute gastroenteritis outbreaks. Therefore, kimchi manufacturers in South Korea should apply chlorine disinfection when using groundwater. Moreover, more stringent sanitation requirements and strict regulations for food companies are recommended.

  6. Impacto de la introducción de la vacuna contra el rotavirus en la hospitalización por gastroenteritis aguda grave en el Hospital del Niño de la Ciudad de Panamá Impact of rotavirus vaccine introduction on hospital admissions for severe acute gastroenteritis at the Children's Hospital in Panama City

    Directory of Open Access Journals (Sweden)

    Javier Nieto Guevara

    2008-09-01

    < 0.05. RESULTS: There was a total of 1 240 episodes of severe acute gastroenteritis in 1 222 children. No significant differences were found between the two study periods regarding the number of complications (P = 0.92 and deaths (P = 1.00. Although there were more episodes of severe acute gastroenteritis after initiating vaccination against human rotavirus than there were in the period prior, the difference was not statistically significant (RR = 1.12; 95%CI: 087-1.44; P = 0.39. There were no significant differences found in the length of hospital stay by age groups studied in each time period. The percent of cases treated with antibiotics was similar in both study periods (29.7% versus 25.2%; P = 0.08. CONCLUSIONS: The introduction of infant rotavirus vaccination was not found to lead to a significant reduction in hospital admission rates for gastroenteritis among children less than 5 years of age. Significant changes in morbidity and in antibiotics use were not found after the introduction of the vaccine.

  7. Etiology and Risk Factors of Acute Gastroenteritis in a Taipei Emergency Department: Clinical Features for Bacterial Gastroenteritis

    Directory of Open Access Journals (Sweden)

    Chao-Chih Lai

    2016-04-01

    Full Text Available Background: The causative pathogen is rarely identified in the emergency department (ED, since the results of cultures are usually unavailable. As a result, antimicrobial treatment may be overused. The aim of our study was to investigate the pathogens, risk factors of acute gastroenteritis, and predictors of acute bacterial gastroenteritis in the ED. Methods: We conducted a matched case-control study of 627 stool samples and 612 matched pairs. Results: Viruses (41.3% were the leading cause of gastroenteritis, with noroviruses (32.2% being the most prevalent, followed by bacteria (26.8% and Giardia lamblia (12.4%. Taking antacids (adjusted odds ratio [aOR] 4.10; 95% confidence interval [CI], 2.57–6.53, household members/classmates with gastroenteritis (aOR 4.69; 95% CI, 2.76–7.96, attending a banquet (aOR 2.29; 95% CI, 1.64–3.20, dining out (aOR 1.70; 95% CI, 1.13–2.54, and eating raw oysters (aOR 3.10; 95% CI, 1.61–5.94 were highly associated with gastroenteritis. Elders (aOR 1.04; 05% CI, 1.02–1.05, those with CRP >10 mg/L (aOR 2.04; 95% CI, 1.15–3.62, or those who were positive for fecal leukocytes (aOR 2.04; 95% CI, 1.15–3.62 or fecal occult blood (aOR 1.97; 95% CI, 1.03–3.77 were more likely to be hospitalized in ED. In addition, presence of fecal leukocytes (time ratio [TR] 1.22; 95% CI, 1.06–1.41, abdominal pain (TR 1.20; 95% CI, 1.07–1.41, and frequency of vomiting (TR 0.79; 95% CI, 0.64–0.98 were significantly associated with the duration of acute gastroenteritis. Presence of fecal leukocytes (aOR 2.08; 95% CI, 1.42–3.05, winter season (aOR 0.45; 95% CI, 0.28–0.74, frequency of diarrhea (aOR 1.69; 95% CI, 1.01–2.83, and eating shrimp or crab (aOR 1.53; 95% CI, 1.05–2.23 were highly associated with bacterial gastroenteritis. The area under the receiver operating characteristic curve of the final model was 0.68 (95% CI, 0.55–0.63. Conclusions: Acute bacterial gastroenteritis was highly associated with

  8. Algorithms for Regular Tree Grammar Network Search and Their Application to Mining Human-viral Infection Patterns.

    Science.gov (United States)

    Smoly, Ilan; Carmel, Amir; Shemer-Avni, Yonat; Yeger-Lotem, Esti; Ziv-Ukelson, Michal

    2016-03-01

    Network querying is a powerful approach to mine molecular interaction networks. Most state-of-the-art network querying tools either confine the search to a prespecified topology in the form of some template subnetwork, or do not specify any topological constraints at all. Another approach is grammar-based queries, which are more flexible and expressive as they allow for expressing the topology of the sought pattern according to some grammar-based logic. Previous grammar-based network querying tools were confined to the identification of paths. In this article, we extend the patterns identified by grammar-based query approaches from paths to trees. For this, we adopt a higher order query descriptor in the form of a regular tree grammar (RTG). We introduce a novel problem and propose an algorithm to search a given graph for the k highest scoring subgraphs matching a tree accepted by an RTG. Our algorithm is based on the combination of dynamic programming with color coding, and includes an extension of previous k-best parsing optimization approaches to avoid isomorphic trees in the output. We implement the new algorithm and exemplify its application to mining viral infection patterns within molecular interaction networks. Our code is available online.

  9. Viral Delivery of dsRNA for Control of Insect Agricultural Pests and Vectors of Human Disease: Prospects and Challenges

    Science.gov (United States)

    Kolliopoulou, Anna; Taning, Clauvis N. T.; Smagghe, Guy; Swevers, Luc

    2017-01-01

    RNAi is applied as a new and safe method for pest control in agriculture but efficiency and specificity of delivery of dsRNA trigger remains a critical issue. Various agents have been proposed to augment dsRNA delivery, such as engineered micro-organisms and synthetic nanoparticles, but the use of viruses has received relatively little attention. Here we present a critical view of the potential of the use of recombinant viruses for efficient and specific delivery of dsRNA. First of all, it requires the availability of plasmid-based reverse genetics systems for virus production, of which an overview is presented. For RNA viruses, their application seems to be straightforward since dsRNA is produced as an intermediate molecule during viral replication, but DNA viruses also have potential through the production of RNA hairpins after transcription. However, application of recombinant virus for dsRNA delivery may not be straightforward in many cases, since viruses can encode RNAi suppressors, and virus-induced silencing effects can be determined by the properties of the encoded RNAi suppressor. An alternative is virus-like particles that retain the efficiency and specificity determinants of natural virions but have encapsidated non-replicating RNA. Finally, the use of viruses raises important safety issues which need to be addressed before application can proceed. PMID:28659820

  10. Viral cross-class serpin inhibits vascular inflammation and T lymphocyte fratricide; a study in rodent models in vivo and human cell lines in vitro.

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    Kasinath Viswanathan

    Full Text Available Poxviruses express highly active inhibitors, including serine proteinase inhibitors (serpins, designed to target host immune defense pathways. Recent work has demonstrated clinical efficacy for a secreted, myxomaviral serpin, Serp-1, which targets the thrombotic and thrombolytic proteases, suggesting that other viral serpins may have therapeutic application. Serp-2 and CrmA are intracellular cross-class poxviral serpins, with entirely distinct functions from the Serp-1 protein. Serp-2 and CrmA block the serine protease granzyme B (GzmB and cysteine proteases, caspases 1 and 8, in apoptotic pathways, but have not been examined for extracellular anti-inflammatory activity. We examined the ability of these cross-class serpins to inhibit plaque growth after arterial damage or transplant and to reduce leukocyte apoptosis. We observed that purified Serp-2, but not CrmA, given as a systemic infusion after angioplasty, transplant, or cuff-compression injury markedly reduced plaque growth in mouse and rat models in vivo. Plaque growth was inhibited both locally at sites of surgical trauma, angioplasty or transplant, and systemically at non-injured sites in ApoE-deficient hyperlipidemic mice. With analysis in vitro of human cells in culture, Serp-2 selectively inhibited T cell caspase activity and blocked cytotoxic T cell (CTL mediated killing of T lymphocytes (termed fratricide. Conversely, both Serp-2 and CrmA inhibited monocyte apoptosis. Serp-2 inhibitory activity was significantly compromised either in vitro with GzmB antibody or in vivo in ApoE/GzmB double knockout mice. Conclusions The viral cross-class serpin, Serp-2, that targets both apoptotic and inflammatory pathways, reduces vascular inflammation in a GzmB-dependent fashion in vivo, and inhibits human T cell apoptosis in vitro. These findings indicate that therapies targeting Granzyme B and/or T cell apoptosis may be used to inhibit T lymphocyte apoptosis and inflammation in response to

  11. Preliminary study on non-viral transfection of F9 (factor IX gene by nucleofection in human adipose-derived mesenchymal stem cells

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    Susana Olmedillas López

    2016-04-01

    Full Text Available Background. Hemophilia is a rare recessive X-linked disease characterized by a deficiency of coagulation factor VIII or factor IX. Its current treatment is merely palliative. Advanced therapies are likely to become the treatment of choice for the disease as they could provide a curative treatment. Methods. The present study looks into the use of a safe non-viral transfection method based on nucleofection to express and secrete human clotting factor IX (hFIX where human adipose tissue derived mesenchymal stem cells were used as target cells in vitro studies and NOD. Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice were used to analyze factor IX expression in vivo studies. Previously, acute liver injury was induced by an injected intraperitoneal dose of 500 mg/kg body weight of acetaminophen. Results. Nucleofection showed a percentage of positive cells ranging between 30.7% and 41.9% and a cell viability rate of 29.8%, and cells were shown to secrete amounts of hFIX between 36.8 and 71.9 ng/mL. hFIX levels in the blood of NSG mice injected with ASCs transfected with this vector, were 2.7 ng/mL 48 h after injection. Expression and secretion of hFIX were achieved both in vitro cell culture media and in vivo in the plasma of mice treated with the transfected ASCs. Such cells are capable of eventually migrating to a previously damaged target tissue (the liver where they secrete hFIX, releasing it to the bloodstream over a period of at least five days from administration. Conclusions. The results obtained in the present study may form a preliminary basis for the establishment of a future ex vivo non-viral gene/cellular safe therapy protocol that may eventually contribute to advancing the treatment of hemophilia.

  12. Understanding Image Virality

    Science.gov (United States)

    2015-06-08

    of images that is most similar to ours is the concurrently introduced viral meme generator of Wang et al., that combines NLP and Computer Vision (low...from what we might expect at a first glance. An analogous scenario researched in NLP is understanding the semantics of “That’s what she said!” jokes...and will require NLP and Computer Vision for understanding. 4.1. Intrinsic context We first examine whether humans and machines can pre- dict just by

  13. Epidemiology and Factors Related to Clinical Severity of Acute Gastroenteritis in Hospitalized Children after the Introduction of Rotavirus Vaccination.

    Science.gov (United States)

    Kim, Ahlee; Chang, Ju Young; Shin, Sue; Yi, Hana; Moon, Jin Soo; Ko, Jae Sung; Oh, Sohee

    2017-03-01

    We aimed to investigate epidemiology and host- and pathogen-related factors associated with clinical severity of acute gastroenteritis (AGE) in children after rotavirus vaccination introduction. Factors assessed included age, co-infection with more than 2 viruses, and virus-toxigenic Clostridium difficile co-detection. Fecal samples and clinical information, including modified Vesikari scores, were collected from hospitalized children with AGE. The presence of enteric viruses and bacteria, including toxigenic C. difficile, was detected by polymerase chain reaction (PCR). Among the 415 children included, virus was detected in stool of 282 (68.0%) children. Co-infection with more than 2 viruses and toxigenic C. difficile were found in 24 (8.5%) and 26 (9.2%) children with viral AGE, respectively. Norovirus (n = 130) infection, including norovirus-associated co-infection, was the most frequent infection, especially in children aged vaccination and availability of molecular diagnostic tests, which often lead to the simultaneous detection of multiple pathogens.

  14. Sialic Acid Binding Properties of Soluble Coronavirus Spike (S1 Proteins: Differences between Infectious Bronchitis Virus and Transmissible Gastroenteritis Virus

    Directory of Open Access Journals (Sweden)

    Christine Winter

    2013-07-01

    Full Text Available The spike proteins of a number of coronaviruses are able to bind to sialic acids present on the cell surface. The importance of this sialic acid binding ability during infection is, however, quite different. We compared the spike protein of transmissible gastroenteritis virus (TGEV and the spike protein of infectious bronchitis virus (IBV. Whereas sialic acid is the only receptor determinant known so far for IBV, TGEV requires interaction with its receptor aminopeptidase N to initiate infection of cells. Binding tests with soluble spike proteins carrying an IgG Fc-tag revealed pronounced differences between these two viral proteins. Binding of the IBV spike protein to host cells was in all experiments sialic acid dependent, whereas the soluble TGEV spike showed binding to APN but had no detectable sialic acid binding activity. Our results underline the different ways in which binding to sialoglycoconjugates is mediated by coronavirus spike proteins.

  15. Viral hepatitis

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Bukh, Jens

    2013-01-01

    With millions of humans infected yearly with HCV, leading to cirrhosis and cancer, a vaccine is urgently needed. Cultured virus particles constitute the antigen in most antiviral vaccines. A study in mice demonstrated induction of neutralizing antibodies by immunization with cell-culture-derived ...

  16. Socio-demographic, Clinical and Laboratory Features of Rotavirus Gastroenteritis in Children Treated in Pediatric Clinic

    OpenAIRE

    Azemi, Mehmedali; Berisha, Majlinda; Ismaili-Jaha, Vlora; Kolgeci, Selim; Avdiu, Muharrem; Jakupi, Xhevat; Hoxha, Rina; Hoxha-Kamberi, Teuta

    2013-01-01

    Aim: The aim of work was presentation of several socio-demographic, clinical and laboratory characteristics of gastroenteritis caused by rotavirus. The examinees and methods: The examinees were children under the age of five years treated at the Pediatric Clinic due to acute gastroenteritis caused by rotavirus. Rotavirus is isolated by method chromatographic immunoassay by Cer Test Biotec. Results: From the total number of patients (850) suffering from acute gastroenteritis, feces test on bac...

  17. Socio-demographic, Epidemiological and Environmental Determinants of Acute Gastroenteritis in Western India

    Directory of Open Access Journals (Sweden)

    Mihir Prafulbhai Rupani

    2016-03-01

    Conclusions: Socio-demographic factors (higher socio-economic status, epidemiological correlates (change in taste of water, another family member been affected with acute gastroenteritis and eating outside food and environmental determinants (waste disposal in a common dump and waste accumulation around house significantly determines the occurrence of cases of acute gastroenteritis. Keywords: case-control studies;diarrhea; epidemiologic determinants; gastroenteritis; social determinants of health. | PubMed

  18. Predominance of genotype P[9]G3 in rotavirus gastroenteritis in Polish children

    OpenAIRE

    Piekarska, Anna; Kacerka, Anna; Majda-Stanis?awska, Ewa; J??wiak, Barbara; Sidorkiewicz, Ma?gorzata

    2015-01-01

    Introduction Rotavirus (RV) infection is the most common cause of gastroenteritis in children. This paper identifies the most common genotypes of rotaviruses isolated from children hospitalized with gastroenteritis and attempts to determine any relationship between infection with a certain rotavirus genotype. Material and methods The investigated group consisted of 68 consecutive children with rotavirus gastroenteritis (confirmed by an agglutination test). Rotavirus genotype was determined in...

  19. BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

    DEFF Research Database (Denmark)

    Arts, Rob J W; Moorlag, Simone J C F M; Novakovic, Boris

    2018-01-01

    The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome......, a heterologous cytokine associated with the induction of trained immunity, but not with the specific IFNγ response. The importance of IL-1β for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human...

  20. STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of Human Adenovirus, Revealing an Important Role of Type I Interferon Response in Viral Control.

    Directory of Open Access Journals (Sweden)

    Karoly Toth

    2015-08-01

    Full Text Available Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout hamsters, and surviving hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type hamsters from being effectively infected to be used as

  1. STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of Human Adenovirus, Revealing an Important Role of Type I Interferon Response in Viral Control.

    Science.gov (United States)

    Toth, Karoly; Lee, Sang R; Ying, Baoling; Spencer, Jacqueline F; Tollefson, Ann E; Sagartz, John E; Kong, Il-Keun; Wang, Zhongde; Wold, William S M

    2015-08-01

    Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout hamsters, and surviving hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type hamsters from being effectively infected to be used as animal models.

  2. Prevalence and viral load of oncogenic human papillomavirus (HPV) in pterygia in multi‐ethnic patients in the Malay Peninsula

    National Research Council Canada - National Science Library

    Chong, Pei Pei; Tung, Chee Hong; Rahman, Nurul Asyikin bt Abdul; Yajima, Misako; Chin, Fee Wai; Yeng, Crystale Lim Siew; Go, Eng Soon; Chan, Cordelia M. L; Yawata, Nobuyo; Yamamoto, Naoki

    2014-01-01

    The aim of the study was to determine the prevalence of human papillomavirus (HPV) in primary and recurrent pterygia samples collected from different ethnic groups in the equatorial Malay Peninsula...

  3. Prospective study of the burden of rotavirus gastroenteritis in Danish children and their families

    DEFF Research Database (Denmark)

    Hoffmann, Thomas; Iturriza, Miren; Faaborg-Andersen, Jens

    2011-01-01

    This was the first study to characterize the total burden of rotavirus gastroenteritis (RVGE) at both hospital and general physician (GP) clinics in Denmark, and also the first to confirm rotavirus (RV) as the leading cause of acute gastroenteritis (GE) among children......This was the first study to characterize the total burden of rotavirus gastroenteritis (RVGE) at both hospital and general physician (GP) clinics in Denmark, and also the first to confirm rotavirus (RV) as the leading cause of acute gastroenteritis (GE) among children...

  4. Household catastrophic healthcare expenditure and impoverishment due to rotavirus gastroenteritis requiring hospitalization in Malaysia

    National Research Council Canada - National Science Library

    Loganathan, Tharani; Lee, Way-Seah; Lee, Kok-Foo; Jit, Mark; Ng, Chiu-Wan

    2015-01-01

    While healthcare costs for rotavirus gastroenteritis requiring hospitalization may be burdensome on households in Malaysia, exploration on the distribution and catastrophic impact of these expenses...

  5. Visualizing viral transport and host infection

    Science.gov (United States)

    Son, Kwangmin; Guasto, Jeffrey; Cubillos-Ruiz, Andres; Sullivan, Matthew; Stocker, Roman; MIT Team

    2013-11-01

    A virus is a non-motile infectious agent that can only replicate inside a living host. They consist of a virus-host encounter/adsorption dynamics and subsequently the effectiveness of various tail morphologies for viral infection. Viral transport and the role of viral morphology in host-virus interactions are critical to our understanding of both ecosystem dynamics and human health, as well as to the evolution of virus morphology.

  6. Outbreak of acute gastroenteritis in an Austrian boarding school, September 2006.

    Science.gov (United States)

    Schmid, D; Gschiel, E; Mann, M; Huhulescu, S; Ruppitsch, W; Bohm, G; Pichler, J; Lederer, I; Hoger, G; Heuberger, S; Allerberger, F

    2007-03-01

    An outbreak of acute gastroenteritis occurred in September 2006 in a boarding school in eastern Austria. Of 113 cases, 101 were hospitalised. In order to identify the outbreak source, a retrospective cohort study on the group at risk was performed, including 222 pupils and 30 staff members. Food exposure in the canteen of the school was identified as the most relevant common link among the cases in the case series investigation. Although the preliminary microbiological investigation made Norovirus infections possible, an in-depth descriptive epidemiological investigation later pointed to food intoxication rather than a viral infection as the cause of the outbreak. The analytical epidemiological investigation implicated boiled rice and chicken wings served in the canteen as the most likely source of the outbreak. Staphylococcus aureus was identified as the causative agent. Further molecular characterisation revealed that the predominant S. aureus type in this outbreak was a new spa type, t2046. The same spa type was isolated from stool specimens of the majority of the cases investigated, from samples of the incriminated boiled rice, and also from a swab of a palmar skin lesion of one of the healthy kitchen workers, who is therefore the most likely source of contamination. This outbreak underlines again the importance of compliance with the basic guidelines for kitchen hygiene.

  7. Effectiveness of rotavirus vaccination in prevention of hospital admissions for rotavirus gastroenteritis among young children in Belgium: case-control study

    Science.gov (United States)

    Braeckman, Tessa; Van Herck, Koen; Meyer, Nadia; Pirçon, Jean-Yves; Soriano-Gabarró, Montse; Heylen, Elisabeth; Zeller, Mark; Azou, Myriam; Capiau, Heidi; De Koster, Jan; Maernoudt, Anne-Sophie; Raes, Marc; Verdonck, Lutgard; Verghote, Marc; Vergison, Anne; Matthijnssens, Jelle; Van Ranst, Marc

    2012-01-01

    Objective To evaluate the effectiveness of rotavirus vaccination among young children in Belgium. Design Prospective case-control study. Setting Random sample of 39 Belgian hospitals, February 2008 to June 2010. Participants 215 children admitted to hospital with rotavirus gastroenteritis confirmed by polymerase chain reaction and 276 age and hospital matched controls. All children were of an eligible age to have received rotavirus vaccination (that is, born after 1 October 2006 and aged ≥14 weeks). Main outcome measure Vaccination status of children admitted to hospital with rotavirus gastroenteritis and matched controls. Results 99 children (48%) admitted with rotavirus gastroenteritis and 244 (91%) controls had received at least one dose of any rotavirus vaccine (Pvaccine accounted for 92% (n=594) of all rotavirus vaccine doses. With hospital admission as the outcome, the unadjusted effectiveness of two doses of the monovalent rotavirus vaccine was 90% (95% confidence interval 81% to 95%) overall, 91% (75% to 97%) in children aged 3-11 months, and 90% (76% to 96%) in those aged ≥12 months. The G2P[4] genotype accounted for 52% of cases confirmed by polymerase chain reaction with eligible matched controls. Vaccine effectiveness was 85% (64% to 94%) against G2P[4] and 95% (78% to 99%) against G1P[8]. In 25% of cases confirmed by polymerase chain reaction with eligible matched controls, there was reported co-infection with adenovirus, astrovirus and/or norovirus. Vaccine effectiveness against co-infected cases was 86% (52% to 96%). Effectiveness of at least one dose of any rotavirus vaccine (intention to vaccinate analysis) was 91% (82% to 95%). Conclusions Rotavirus vaccination is effective for the prevention of admission to hospital for rotavirus gastroenteritis among young children in Belgium, despite the high prevalence of G2P[4] and viral co-infection. PMID:22875947

  8. Proteome profile of swine testicular cells infected with porcine transmissible gastroenteritis coronavirus.

    Directory of Open Access Journals (Sweden)

    Ruili Ma

    Full Text Available The interactions occurring between a virus and a host cell during a viral infection are complex. The purpose of this paper was to analyze altered cellular protein levels in porcine transmissible gastroenteritis coronavirus (TGEV-infected swine testicular (ST cells in order to determine potential virus-host interactions. A proteomic approach using isobaric tags for relative and absolute quantitation (iTRAQ-coupled two-dimensional liquid chromatography-tandem mass spectrometry identification was conducted on the TGEV-infected ST cells. The results showed that the 4-plex iTRAQ-based quantitative approach identified 4,112 proteins, 146 of which showed significant changes in expression 48 h after infection. At 64 h post infection, 219 of these proteins showed significant change, further indicating that a larger number of proteomic changes appear to occur during the later stages of infection. Gene ontology analysis of the altered proteins showed enrichment in multiple biological processes, including cell adhesion, response to stress, generation of precursor metabolites and energy, cell motility, protein complex assembly, growth, developmental maturation, immune system process, extracellular matrix organization, locomotion, cell-cell signaling, neurological system process, and cell junction organization. Changes in the expression levels of transforming growth factor beta 1 (TGF-β1, caspase-8, and heat shock protein 90 alpha (HSP90α were also verified by western blot analysis. To our knowledge, this study is the first time the response profile of ST host cells following TGEV infection has been analyzed using iTRAQ technology, and our description of the late proteomic changes that are occurring after the time of vigorous viral production are novel. Therefore, this study provides a solid foundation for further investigation, and will likely help us to better understand the mechanisms of TGEV infection and pathogenesis.

  9. Detection of Aichi virus with antibody targeting of conserved viral protein 1 epitope.

    Science.gov (United States)

    Chen, Yao-Shen; Chen, Bao-Chen; Lin, You-Sheng; Chang, Jenn-Tzong; Huang, Tsi-Shu; Chen, Jih-Jung; Chang, Tsung-Hsien

    2013-10-01

    Aichi virus (AiV) is an emerging single-stranded, positive-sense, non-enveloped RNA virus in the Picornaviridae that causes acute gastroenteritis in humans. The first case of AiV infection in Taiwan was diagnosed in a human neonate with enterovirus-associated symptoms; the virus was successfully isolated and propagated. To establish a method to detect AiV, we analyzed the antigen epitope and generated a polyclonal antibody against AiV viral protein 1 (VP1). This peptide-purified anti-AiV VP1 antibody showed high specificity against AiV VP1 without cross-reaction to nine other tested strains of Picornaviruses. The anti-AiV VP1 antibody was used in immunofluorescence analysis, immunoblotting, and enzyme-linked immunosorbent assay to elucidate the cell tropism and replication kinetics of AiV. Use of the anti-AiV VP1 antibody also revealed AiV infection restriction with interferon type I and polyI/C antiviral treatment. The AiV infection and detection system may provide an in vitro platform for AiV virology study.

  10. A novel virally inactivated human platelet lysate preparation rich in TGF-beta, EGF and IGF, and depleted of PDGF and VEGF.

    Science.gov (United States)

    Burnouf, Pierre-Alain; Juan, Po-Kai; Su, Chen-Yao; Kuo, Ya-Po; Chou, Ming-Li; Su, Ching-Hua; Tseng, Yu-Hung; Lin, Che-Tong; Burnouf, Thierry

    2010-08-06

    There is emerging interest in the use of standardized virally inactivated human platelet lysate preparations rich in GFs (growth factors) for cell cultures, cell therapy and clinical applications. In the present paper, we report a simple process to prepare a virally inactivated platelet lysate preparation rich in TGF-beta1 (transforming growth factor-beta1), EGF (epidermal growth factor) and IGF (insulin-like growth factor) and depleted of PDGF (platelet-derived growth factor) and VEGF (vascular endothelial growth factor). Apheresis platelet concentrates were treated by the S/D (solvent/detergent) viral inactivation procedure, then subjected to an oil extraction followed by adsorption with activated charcoal and finally sterile-filtered. The resulting preparation contained a mean of 368.4, 2.4 and 54.7 ng/ml of TGF-beta1, EGF and IGF respectively. PDGF-AB and VEGF were essentially completely removed by the charcoal treatment. The mean albumin, IgG, IgM and IgA and fibrinogen contents were approx. 40.0, 8.5, 0.87, 1.66 and 2.65 mg/ml respectively, cholesterol and triglycerides were at 15 and 20.7 mg/ml respectively and TnBP (tri-n-butyl phosphate) and Triton X-45 were at 8.7 and 8.8 p.p.m. respectively. Supplementing MEM (minimum essential medium) with 1-10% of this S/D-treated platelet lysate promoted the proliferation of MG63 and SIRC cell lines as well as, or better than, 10% (v/v) FBS (fetal bovine serum), as based on the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. The process used to prepare such S/D-treated platelet lysates is easily scalable for industrial production. Our results open up the possibility to evaluate the potential of this new preparation for stem cell expansion and/or bone tissue engineering and regeneration.

  11. In vitro non-viral lipofectamine delivery of the gene for glial cell line-derived neurotrophic factor to human umbilical cord blood CD34+ cells.

    Science.gov (United States)

    Yu, Guolong; Borlongan, Cesar V; Ou, Yali; Stahl, Christine E; Yu, SeongJin; Bae, EungKyung; Kaneko, Yuji; Yang, Tianlun; Yuan, Chunjun; Fang, Li

    2010-04-14

    Using a lipofection technique, we explored a non-viral delivery of plasmid DNA encoding a rat pGDNF (glial cell line-derived neurotrophic factor) to CD34+ cells derived from human umbilical cord blood (HUCB) cells in order to obtain cells stably expressing the GDNF gene. The target gene GDNF was amplified from cortex cells of newborn Sprague-Dawley rats by reverse transcriptase polymerase chain reaction (RT-PCR) and inserted into vector pEGFP-N1 to construct the eukaryotic expression vector pEGFP/GDNF. The positive clones were identified by sequencing and endonuclease digestion. The expression of pEGFP/GDNF-transfected HUCB cells CD34+ was examined by ELISA. Single fragment of 640 bp was obtained after the rat GDNF cDNA was amplified by RT-PCR. Two fragments of about 4.3 kb and 640 pb were obtained after digestion of recombinant plasmid pEGFP/GDNF with XhoI/KpnI. The nucleic acid fragment of 640 bp was confirmed to agree well with the sequence of GDNF gene published by GenBank. The expression of GDNF mRNA and the level of GDNF from pEGFP/GDNF-transfected CD34+ cells were increased substantially, compared with pEGFP control plasmid transfected CD34+ cells (P<0.05). Moreover, co-culture of primary rat cells with the pEGFP/GDNF-transfected CD34+ cells promoted enhanced neuroprotection against oxygen-glucose deprivation induced cell dysfunctions. The present results support the use of the non-viral plasmid liposome for therapeutic gene expression for stem cell therapy. Copyright 2010 Elsevier B.V. All rights reserved.

  12. Circulation of Aichi virus genotype B strains in children with acute gastroenteritis in India.

    Science.gov (United States)

    Verma, H; Chitambar, S D; Gopalkrishna, V

    2011-11-01

    Acute gastroenteritis (AG) is considered as one of the major health problems affecting humans of all ages. A number of viruses have been recognized as important causes of this disease. Recently, Aichi virus has been shown to play an aetiological role in sporadic infections and outbreaks of AG. A study on surveillance of enteric viruses was conducted during 2004-2008 in three cities in Maharashtra state, western India. A total of 1240 stool specimens from children aged ≤8 years hospitalized for AG were screened for the presence of Aichi virus by RT-PCR of the 3C-3D junction region followed by sequencing for the identification of genotype. Aichi virus was detected at a prevalence of 1·1% in the Aichi virus genotype B in India.

  13. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression

    NARCIS (Netherlands)

    de Waal Malefyt, R.; Haanen, J.; Spits, H.; Roncarolo, M. G.; te Velde, Anje; Figdor, C.; Johnson, K.; Kastelein, R.; Yssel, H.; de Vries, J. E.

    1991-01-01

    Interleukin 10 (IL-10) and viral IL-10 (v-IL-10) strongly reduced antigen-specific proliferation of human T cells and CD4+ T cell clones when monocytes were used as antigen-presenting cells. In contrast, IL-10 and v-IL-10 did not affect the proliferative responses to antigens presented by autologous

  14. NSP4 antibody levels in rotavirus gastroenteritis patients with seizures.

    Science.gov (United States)

    Yeom, Jung Sook; Kim, Young-Soo; Jun, Jin-Su; Do, Hyun Jung; Park, Ji Sook; Seo, Ji-Hyun; Park, Eun Sil; Lim, Jae-Young; Woo, Hyang-Ok; Park, Chan-Hoo; Youn, Hee-Shang

    2017-03-01

    Rotavirus nonstructural protein 4 (NSP4) has been suggested as a pathogen of rotavirus-associated seizures. We investigated pre-existing serum antibodies against NSP4 and VP6 (the most highly immunogenic rotavirus protein) in patients with rotavirus gastroenteritis and its correlation with the occurrence of seizures. With an enzyme-linked immunosorbent assay, IgG and IgA titers against NSP4 (genotype [A] and [B]) and VP6 were measured in acute-phase sera of 202 children aged 0.5-6.0 years with rotavirus gastroenteritis. The clinical characteristics and antibody levels were compared between patients with (seizure group) and without seizures (non-seizure group). The non-seizure and seizure groups comprised 173 and 29 patients, respectively. Age, sex, hospital stay, presence of fever, white blood cell counts, C-reactive protein, vaccine status, IgG/IgA titers for VP6, and IgA titers for both NSP4s did not differ between the groups. The seizure group showed a lower level of IgG against NSP4 [A] (184.5 vs. 163.0 U/mL; P = 0.03) and NSP4 [B] (269.0 vs. 196.0 U/mL; P = 0.02). Delayed sampling time from the onset of gastroenteritis symptoms (3 vs. 2 days; P = 0.02) and lower serum sodium level (133.4 vs. 136.3 mEq/L; P rotavirus-associated seizures. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  15. Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis.

    Science.gov (United States)

    Nguyen, Thong Van; Pham, Van Hung; Abe, Kenji

    2015-01-01

    Development of congenital rubella syndrome associated with rubella virus infection during pregnancy is clinically important, but the pathogenicity of the virus remains unclear. Pathological examination was conducted on 3 aborted fetuses with congenital rubella infection. At autopsy, all 3 aborted fetuses showed congenital cataract confirmed by gross observation. Rubella virus infection occurred via systemic organs including circulating hematopoietic stem cells confirmed by immunohistochemical and molecular investigations, and major histopathogical changes were found in the liver. It is noteworthy that the virus infected the ciliary body of the eye, suggesting a possible cause of cataracts. Our study based on the pathological examination demonstrated that the rubella virus infection occurred via systemic organs of human fetuses. This fact was confirmed by immunohistochemistry and direct detection of viral RNA in multiple organs. To the best of our knowledge, this study is the first report demonstrating that the rubella virus infection occurred via systemic organs of the human body. Importantly, virus infection of the ciliary body could play an important role in cataractogenesis.

  16. Involvement of CD252 (CD134L) and IL-2 in the expression of cytotoxic proteins in bacterial- or viral-activated human T cells.

    Science.gov (United States)

    Walch, Michael; Rampini, Silvana K; Stoeckli, Isabelle; Latinovic-Golic, Sonja; Dumrese, Claudia; Sundstrom, Hanna; Vogetseder, Alexander; Marino, Joseph; Glauser, Daniel L; van den Broek, Maries; Sander, Peter; Groscurth, Peter; Ziegler, Urs

    2009-06-15

    Regulation of cytotoxic effector molecule expression in human CTLs after viral or bacterial activation is poorly understood. By using human autologous dendritic cells (DCs) to prime T lymphocytes, we found perforin only highly up-regulated in virus- (HSV-1, vaccinia virus) but not in intracellular bacteria- (Listeria innocua, Listeria monocytogenes, Mycobacterium tuberculosis, Chlamydophila pneumoniae) activated CTLs. In contrast, larger quantities of IFN-gamma and TNF-alpha were produced in Listeria-stimulated cultures. Granzyme B and granulysin were similarly up-regulated by all tested viruses and intracellular bacteria. DCs infected with HSV-1 showed enhanced surface expression of the costimulatory molecule CD252 (CD134L) compared with Listeria-infected DC and induced enhanced secretion of IL-2. Adding blocking CD134 or neutralizing IL-2 Abs during T cell activation reduced the HSV-dependent up-regulation of perforin. These data indicate a distinct CTL effector function in response to intracellular pathogens triggered via differing endogenous IL-2 production upon costimulation through CD252.

  17. Detection of adeno-associated virus in human semen: does viral infection play a role in the pathogenesis of male infertility?

    Science.gov (United States)

    Rohde, V; Erles, K; Sattler, H P; Derouet, H; Wullich, B; Schlehofer, J R

    1999-11-01

    To evaluate the occurrence of adeno-associated virus (AAV) DNA and/or human papillomavirus (HPV) DNA in the semen of infertile men as a possible factor in the pathogenesis of male infertility. Descriptive pilot study. University-based diagnostic and research laboratory. Semen specimens were collected from 30 men with diagnosed infertility and from 8 control subjects. Diagnostic spermiograms were made and the semen specimens were separated into seminal fluid, nonspermatozoal cells, and spermatozoa using a Ficoll gradient technique. The presence of AAV and HPV DNA in the different fractions of the ejaculates from the infertile men and the control subjects was detected by polymerase chain reaction. Semen quality was analyzed according to World Health Organization guidelines. Adeno-associated virus DNA was detected in 30% (9/30) of the ejaculates from the infertile men. No AAV DNA was found in the ejaculates from the 8 control subjects. In 8 of 9 samples, AAV DNA could be found only in the spermatozoal fraction of the specimen. Seven of 9 semen specimens that contained viral DNA also demonstrated oligoasthenozoospermia. Both AAV and HPV DNA was found in the spermatozoal fraction of 3 of 30 specimens. The data demonstrate for the first time the occurrence of AAV infection in human semen. Sperm motility seems to be affected by the presence of AAV.

  18. Crohn's Disease Exacerbation Induced by Edwardsiella tarda Gastroenteritis.

    Science.gov (United States)

    Arya, Aman V; Rostom, Alaa; Dong, Wei-Feng; Flynn, Andrew N

    2011-09-01

    Exacerbations of Crohn's disease are not infrequently associated with bacterial gastroenteritis. The recognition of synchronous infections in such patients is vital for the initiation of appropriate antimicrobial therapy. Furthermore, the detection of active bacterial infections may lead the clinician to delay starting biological therapy. We report here a man presenting with an exacerbation of his Crohn's disease during a trip to Thailand. Stool cultures were positive for the unusual gut pathogen Edwardsiella tarda. The patient's symptoms resolved with concurrent antibiotic and steroid therapy. This finding demonstrates the value of performing stool culture in all patients presenting with exacerbations of inflammatory bowel diseases.

  19. Crohn’s Disease Exacerbation Induced by Edwardsiella tarda Gastroenteritis

    Directory of Open Access Journals (Sweden)

    Aman V. Arya

    2011-10-01

    Full Text Available Exacerbations of Crohn’s disease are not infrequently associated with bacterial gastroenteritis. The recognition of synchronous infections in such patients is vital for the initiation of appropriate antimicrobial therapy. Furthermore, the detection of active bacterial infections may lead the clinician to delay starting biological therapy. We report here a man presenting with an exacerbation of his Crohn’s disease during a trip to Thailand. Stool cultures were positive for the unusual gut pathogen Edwardsiella tarda. The patient’s symptoms resolved with concurrent antibiotic and steroid therapy. This finding demonstrates the value of performing stool culture in all patients presenting with exacerbations of inflammatory bowel diseases.

  20. [Lactic acidosis due to metformin accumulation complicating acute gastroenteritis].

    Science.gov (United States)

    DŽupová, Olga; Kulichová, Jana

    2016-12-01

    Lactic acidosis is the most severe adverse effect associated with metformin therapy of type 2 diabetes mellitus. The risk increases in patients with impaired renal function, most commonly due to diabetic nephropathy, and may be augmented when concurrent medication with a negative impact on renal function is used. The authors present a series of three patients who were admitted to a department of infectious diseases for acute gastroenteritis and within a few hours developed shock syndrome caused by severe lactic acidosis due to accumulation of metformin.

  1. The role of Campylobacter jejuni cytolethal distending toxin in gastroenteritis

    DEFF Research Database (Denmark)

    Mortensen, Ninell P; Schiellerup, Peter; Boisen, Nadia

    2011-01-01

    The role of Campylobacter jejuni cytolethal distending toxin (CDT) on clinical outcome after gastroenteritis was investigated. Clinical data, blood serum samples, and Campylobacter spp. isolated, from each of 30 patients were collected over a period of 6 months. The CDT encoding genes, cdt......ABC, characterized by PCR, revealed that all but one of the C. jejuni strains had the wild-type sequence. Sequencing of cdtABC from this strain showed two major deletions. From all of the strains, CDT titers were determined, and toxin neutralizing antibodies were documented using an in vitro assay. Three...

  2. Lactose malabsorption during gastroenteritis, assessed by the hydrogen breath test.

    OpenAIRE

    Gardiner, A J; Tarlow, M. J.; Sutherland, I T; Sammons, H. G.

    1981-01-01

    Thirty-eight infants and young children with gastroenteritis were investigated for lactose malabsorption. Each of them was given an oral lactose load of either 0.5 g/kg or 2 g/kg after which breath hydrogen excretion was measured, and each was observed to see if he had clinical symptoms of lactose intolerance. Only one patient, given 2 g/kg lactose, had clinical intolerance. His breath hydrogen excretion however was negative. Three of 18 patients given 0.5 g/kg lactose had positive breath hyd...

  3. Exploiting high-throughput screens to optimize Adeno-Associated Viral Vectors for gene transfer into primary human keratinocytes

    OpenAIRE

    Sallach, Jessica

    2014-01-01

    Chronic non-healing wounds such as diabetic ulcers or burns represent a devastating health problem with significant clinical, physical and social implications. The healing can be frustrating and painful for patients. The difficult healing process requires advanced therapeutic strategies such as the use of primary human keratinocytes (HK) as autologous transplants, which may be considered for clinical use. To improve engraftment or to introduce therapeutic genes into primary HK, efficient and ...

  4. Long-term risk of cervical intraepithelial neoplasia grade 3 or worse according to high-risk human papillomavirus genotype and semi-quantitative viral load among 33,288 women with normal cervical cytology

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

    2015-01-01

    In this prospective cohort study, we estimated the long-term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high-risk human papillomavirus (hrHPV) genotype and semi-quantitative viral load at baseline among 33,288 women aged 14-90 years with normal baseline cytology. During...... 2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women...

  5. Neutralizing antibody response during human immunodeficiency virus type 1 infection: type and group specificity and viral escape

    DEFF Research Database (Denmark)

    Arendrup, M; Sönnerborg, A; Svennerholm, B

    1993-01-01

    demonstrated, suggesting that the majority of the change in neutralization sensitivity is driven by the selective pressure of type-specific NA. Furthermore, no differences were observed in sensitivity to neutralization by anti-carbohydrate neutralizing monoclonal antibodies or the lectin concanavalin A......The paradox that group-specific neutralizing antibodies (NA) exist in the majority of human immunodeficiency virus type 1 (HIV-1)-infected patients, whereas the NA response against autologous HIV-1 virus isolates is highly type-specific, motivated us to study the type- and group-specific NA...

  6. An epidemiological perspective on gastroenteritis in child day care centers : Assessment of impact and risk

    NARCIS (Netherlands)

    Enserink, R.

    2014-01-01

    The impact of gastroenteritis related to Dutch DCCs is substantial, particularly among the very young attendees. Attending a DCC roughly doubles a child’s probability of experiencing an episode of gastroenteritis that requires a visit to a general practitioner or hospital. A child might experience a

  7. Household Catastrophic Healthcare Expenditure and Impoverishment Due to Rotavirus Gastroenteritis Requiring Hospitalization in Malaysia

    OpenAIRE

    Loganathan, T.; Lee, WS; Lee, KF; Jit, M; Ng, CW

    2015-01-01

    Background While healthcare costs for rotavirus gastroenteritis requiring hospitalization may be burdensome on households in Malaysia, exploration on the distribution and catastrophic impact of these expenses on households are lacking. Objectives We assessed the economic burden, levels and distribution of catastrophic healthcare expenditure, the poverty impact on households and inequities related to healthcare payments for acute gastroenteritis requiring hospitalization in Malaysia. Methods A...

  8. Post-Transcriptional Regulation of KLF4 by High-Risk Human Papillomaviruses Is Necessary for the Differentiation-Dependent Viral Life Cycle.

    Directory of Open Access Journals (Sweden)

    Vignesh Kumar Gunasekharan

    2016-07-01

    Full Text Available Human papillomaviruses (HPVs are epithelial tropic viruses that link their productive life cycles to the differentiation of infected host keratinocytes. A subset of the over 200 HPV types, referred to as high-risk, are the causative agents of most anogenital malignancies. HPVs infect cells in the basal layer, but restrict viral genome amplification, late gene expression, and capsid assembly to highly differentiated cells that are active in the cell cycle. In this study, we demonstrate that HPV proteins regulate the expression and activities of a critical cellular transcription factor, KLF4, through post-transcriptional and post-translational mechanisms. Our studies show that KLF4 regulates differentiation as well as cell cycle progression, and binds to sequences in the upstream regulatory region (URR to regulate viral transcription in cooperation with Blimp1. KLF4 levels are increased in HPV-positive cells through a post-transcriptional mechanism involving E7-mediated suppression of cellular miR-145, as well as at the post-translational level by E6-directed inhibition of its sumoylation and phosphorylation. The alterations in KLF4 levels and functions results in activation and suppression of a subset of KLF4 target genes, including TCHHL1, VIM, ACTN1, and POT1, that is distinct from that seen in normal keratinocytes. Knockdown of KLF4 with shRNAs in cells that maintain HPV episomes blocked genome amplification and abolished late gene expression upon differentiation. While KLF4 is indispensable for the proliferation and differentiation of normal keratinocytes, it is necessary only for differentiation-associated functions of HPV-positive keratinocytes. Increases in KLF4 levels alone do not appear to be sufficient to explain the effects on proliferation and differentiation of HPV-positive cells indicating that additional modifications are important. KLF4 has also been shown to be a critical regulator of lytic Epstein Barr virus (EBV replication

  9. DETECTION OF HUMAN ENTEROVIRUS AND ADENOVIRUS IN SHELLFISH COLLECTED IN MOROCCO MEDITERRANEAN COAST

    Directory of Open Access Journals (Sweden)

    Laila Benabbes

    2013-10-01

    Full Text Available The aim of this study was the screening for the presence of enteric human virus in shellfish (clam and cockle collected from two production area in Moroccan Mediterranean coast. Between October 2006 and April 2008, forty four samples were collected and tested for viral contamination using cell culture (HEp-2 and Vero cells and integrated cell culture PCR. Overall, 88.6 % of all analysed samples were contaminated by at least one of the studied viruses, Adenovirus was detected in 52.3 % of the samples and Enterovirus in 36.3%. The presence of viruses in shellfish production area can represent a potential health risk by causing gastroenteritis. The procedure used in this study may be a tool for monitoring shellfish viral contamination in Morocco.

  10. Characterization of cognitive deficits in rats overexpressing human alpha-synuclein in the ventral tegmental area and medial septum using recombinant adeno-associated viral vectors.

    Science.gov (United States)

    Hall, Hélène; Jewett, Michael; Landeck, Natalie; Nilsson, Nathalie; Schagerlöf, Ulrika; Leanza, Giampiero; Kirik, Deniz

    2013-01-01

    Intraneuronal inclusions containing alpha-synuclein (a-syn) constitute one of the pathological hallmarks of Parkinson's disease (PD) and are accompanied by severe neurodegeneration of A9 dopaminergic neurons located in the substantia nigra. Although to a lesser extent, A10 dopaminergic neurons are also affected. Neurodegeneration of other neuronal populations, such as the cholinergic, serotonergic and noradrenergic cell groups, has also been documented in PD patients. Studies in human post-mortem PD brains and in rodent models suggest that deficits in cholinergic and dopaminergic systems may be associated with the cognitive impairment seen in this disease. Here, we investigated the consequences of targeted overexpression of a-syn in the mesocorticolimbic dopaminergic and septohippocampal cholinergic pathways. Rats were injected with recombinant adeno-associated viral vectors encoding for either human wild-type a-syn or green fluorescent protein (GFP) in the ventral tegmental area and the medial septum/vertical limb of the diagonal band of Broca, two regions rich in dopaminergic and cholinergic neurons, respectively. Histopathological analysis showed widespread insoluble a-syn positive inclusions in all major projections areas of the targeted nuclei, including the hippocampus, neocortex, nucleus accumbens and anteromedial striatum. In addition, the rats overexpressing human a-syn displayed an abnormal locomotor response to apomorphine injection and exhibited spatial learning and memory deficits in the Morris water maze task, in the absence of obvious spontaneous locomotor impairment. As losses in dopaminergic and cholinergic immunoreactivity in both the GFP and a-syn expressing animals were mild-to-moderate and did not differ from each other, the behavioral impairments seen in the a-syn overexpressing animals appear to be determined by the long term persisting neuropathology in the surviving neurons rather than by neurodegeneration.

  11. Characterization of cognitive deficits in rats overexpressing human alpha-synuclein in the ventral tegmental area and medial septum using recombinant adeno-associated viral vectors.

    Directory of Open Access Journals (Sweden)

    Hélène Hall

    Full Text Available Intraneuronal inclusions containing alpha-synuclein (a-syn constitute one of the pathological hallmarks of Parkinson's disease (PD and are accompanied by severe neurodegeneration of A9 dopaminergic neurons located in the substantia nigra. Although to a lesser extent, A10 dopaminergic neurons are also affected. Neurodegeneration of other neuronal populations, such as the cholinergic, serotonergic and noradrenergic cell groups, has also been documented in PD patients. Studies in human post-mortem PD brains and in rodent models suggest that deficits in cholinergic and dopaminergic systems may be associated with the cognitive impairment seen in this disease. Here, we investigated the consequences of targeted overexpression of a-syn in the mesocorticolimbic dopaminergic and septohippocampal cholinergic pathways. Rats were injected with recombinant adeno-associated viral vectors encoding for either human wild-type a-syn or green fluorescent protein (GFP in the ventral tegmental area and the medial septum/vertical limb of the diagonal band of Broca, two regions rich in dopaminergic and cholinergic neurons, respectively. Histopathological analysis showed widespread insoluble a-syn positive inclusions in all major projections areas of the targeted nuclei, including the hippocampus, neocortex, nucleus accumbens and anteromedial striatum. In addition, the rats overexpressing human a-syn displayed an abnormal locomotor response to apomorphine injection and exhibited spatial learning and memory deficits in the Morris water maze task, in the absence of obvious spontaneous locomotor impairment. As losses in dopaminergic and cholinergic immunoreactivity in both the GFP and a-syn expressing animals were mild-to-moderate and did not differ from each other, the behavioral impairments seen in the a-syn overexpressing animals appear to be determined by the long term persisting neuropathology in the surviving neurons rather than by neurodegeneration.

  12. Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import

    Directory of Open Access Journals (Sweden)

    Fowke Keith R

    2005-10-01

    Full Text Available Abstract Background In addition to mediating the integration process, HIV-1 integrase (IN has also been implicated in different steps during viral life cycle including reverse transcription and viral DNA nuclear import. Although the karyophilic property of HIV-1 IN has been well demonstrated using a variety of experimental approaches, the definition of domain(s and/or motif(s within the protein that mediate viral DNA nuclear import and its mechanism are still disputed and controversial. In this study, we performed mutagenic analyses to investigate the contribution of different regions in the C-terminal domain of HIV-1 IN to protein nuclear localization as well as their effects on virus infection. Results Our analysis showed that replacing lysine residues in two highly conserved tri-lysine regions, which are located within previously described Region C (235WKGPAKLLWKGEGAVV and sequence Q (211KELQKQITK in the C-terminal domain of HIV-1 IN, impaired protein nuclear accumulation, while mutations for RK263,4 had no significant effect. Analysis of their effects on viral infection in a VSV-G pseudotyped RT/IN trans-complemented HIV-1 single cycle replication system revealed that all three C-terminal mutant viruses (KK215,9AA, KK240,4AE and RK263,4AA exhibited more severe defect of induction of β-Gal positive cells and luciferase activity than an IN class 1 mutant D64E in HeLa-CD4-CCR5-β-Gal cells, and in dividing as well as non-dividing C8166 T cells, suggesting that some viral defects are occurring prior to viral integration. Furthermore, by analyzing viral DNA synthesis and the nucleus-associated viral DNA level, the results clearly showed that, although all three C-terminal mutants inhibited viral reverse transcription to different extents, the KK240,4AE mutant exhibited most profound effect on this step, whereas KK215,9AA significantly impaired viral DNA nuclear import. In addition, our analysis could not detect viral DNA integration in each C

  13. Viral diseases affecting the pleura.

    Science.gov (United States)

    Nestor, Jennings; Huggins, Terrill; Kummerfeldt, Carlos; DiVietro, Matthew; Walters, Kenneth; Sahn, Steven

    2013-10-01

    Viruses affect the human body in multiple ways producing various disease states. The infections of the pulmonary parenchyma have been well described. However, there has been no current review of the literature pertaining to the pleura. To review the available literature pertaining to diseases of the pleura that are caused by viral infections. A Medline search was performed and available research and review articles relating to viral infections that resulted in pleural effusions, pleural masses, pleural thickening, and pleural nodularity were reviewed. There are numerous viruses that cause diseases of the pleura. Pleural effusions and lesions within the pleura are the most common presentation of the disease state. Polymerase chain reaction has the potential to further diagnose viral infections and expand our knowledge base in this field. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates.

    Science.gov (United States)

    Kotterman, M A; Yin, L; Strazzeri, J M; Flannery, J G; Merigan, W H; Schaffer, D V

    2015-02-01

    Gene delivery vectors based on adeno-associated viruses (AAV) have exhibited promise in both preclinical disease models and human clinical trials for numerous disease targets, including the retinal degenerative disorders Leber's congenital amaurosis and choroideremia. One general challenge for AAV is that preexisting immunity, as well as subsequent development of immunity following vector administration, can severely inhibit systemic AAV vector gene delivery. However, the role of neutralizing antibodies (NABs) in AAV transduction of tissues considered to be immune privileged, such as the eye, is unclear in large animals