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Sample records for sustain persistent viral

  1. T Cell Exhaustion During Persistent Viral Infections

    Science.gov (United States)

    Kahan, Shannon M.; Wherry, E. John; Zajac, Allan J.

    2015-01-01

    Although robust and highly effective anti-viral T cells contribute to the clearance of many acute infections, viral persistence is associated with the development of functionally inferior, exhausted, T cell responses. Exhaustion develops in a step-wise and progressive manner, ranges in severity, and can culminate in the deletion of the anti-viral T cells. This disarming of the response is consequential as it compromises viral control and potentially serves to dampen immune-mediated damage. Exhausted T cells are unable to elaborate typical anti-viral effector functions. They are characterized by the sustained upregulation of inhibitory receptors and display a gene expression profile that distinguishes them from prototypic effector and memory T cell populations. In this review we discuss the properties of exhausted T cells; the virological and immunological conditions that favor their development; the cellular and molecular signals that sustain the exhausted state; and strategies for preventing and reversing exhaustion to favor viral control. PMID:25620767

  2. Viral Innovation, Sustainability, and Excellence

    DEFF Research Database (Denmark)

    Edgeman, Rick; Eskildsen, Jacob Kjær

    for these models include Biophysical/Environmental, Business/Economic, and Societal dimensions with the BEST model adding a Technological dimension that refers predominantly to infrastructure, that is, to the built-environment. Integration across these sustainability dimensions is challenging, but can......Enterprises strive to be economically sustainable. In doing so, they either contribute to or detract from environmental and social sustainability. Sustainability is hence multi-dimensional with formulations that include the familiar triple-bottom-line and BEST models. Any assessment regimen...... what is henceforth called “viral innovation”. Evidence of growing global emphasis on environmental and social sustainability is provided by the United Nations Global Compact (http://www.unglobalcompact.org/), the Pearl Initiative in the Middle East (http...

  3. Does persisting fear sustain catatonia?

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    Fink, M; Shorter, E

    2017-11-01

    To examine the psychological substrate of catatonia. Reviewing the historical descriptions and explanations of catatonic behaviours by clinicians from its delineation in the 19th century to the present. Patients with catatonia are often haunted by fears and terrors; this has not been widely appreciated, and certainly was lost from view in the days when catatonia was considered a subtype of schizophrenia. The report contributes to resolving a major question in catatonia: is the mind in stupor inactive, as the blank state that we picture in anesthetized patients, or is the mind active, so preoccupied as to exclude all other influences. Persistent fear occupies the mind of catatonic patients. The signs of catatonia are adaptations to persistent fear, akin to tonic immobilization. The relief afforded by sedation supports this interpretation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Towards Sustainability in Viral Marketing with User Engaging Supporting Campaigns

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    Jarosław Jankowski

    2017-12-01

    Full Text Available While viral marketing has captured substantial academic and professional interest, the processes that underpin successful viral marketing campaigns remain poorly understood. High competition and pressure for successful campaigns lead to strategies based on persuasion, unsolicited messages, and other techniques that negatively affect brand perception. The need for more sustainable strategies with a limited negative impact on web users is observed. Therefore, the current study examines the effectiveness of viral marketing and a supporting campaign, where the main goal was to increase user engagement and overall campaign performance. Supporting campaigns were evaluated, to determine whether they enhanced viral activity, but without the need for high persuasion or intrusive techniques. Results showed that supporting actions could be integrated with lower performing campaigns to increase their effectiveness. Apart from the main scientific goal that is presented, the study demonstrates how virtual worlds can provide a laboratory-like environment for identifying the processes that underpin viral marketing.

  5. Viral persistence, liver disease and host response in Hepatitis C-like virus rat model

    DEFF Research Database (Denmark)

    Trivedi, Sheetal; Murthy, Satyapramod; Sharma, Himanshu

    2018-01-01

    cleavage sites and secondary structures in the viral 5' and 3' UTRs. We used site-directed and random mutagenesis to determine that only the first of the two miR-122 seed sites in viral 5'UTR is required for viral replication and persistence in rats. Next, we used the clone derived virus progeny to infect...

  6. DNA cleavage enzymes for treatment of persistent viral infections: Recent advances and the pathway forward

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Nicholas D., E-mail: nweber@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Aubert, Martine, E-mail: maubert@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Dang, Chung H., E-mail: cdang@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Stone, Daniel, E-mail: dstone2@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Jerome, Keith R., E-mail: kjerome@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Department of Microbiology, University of Washington, Seattle, WA 98195 (United States)

    2014-04-15

    Treatment for most persistent viral infections consists of palliative drug options rather than curative approaches. This is often because long-lasting viral DNA in infected cells is not affected by current antivirals, providing a source for viral persistence and reactivation. Targeting latent viral DNA itself could therefore provide a basis for novel curative strategies. DNA cleavage enzymes can be used to induce targeted mutagenesis of specific genes, including those of exogenous viruses. Although initial in vitro and even in vivo studies have been carried out using DNA cleavage enzymes targeting various viruses, many questions still remain concerning the feasibility of these strategies as they transition into preclinical research. Here, we review the most recent findings on DNA cleavage enzymes for human viral infections, consider the most relevant animal models for several human viral infections, and address issues regarding safety and enzyme delivery. Results from well-designed in vivo studies will ideally provide answers to the most urgent remaining questions, and allow continued progress toward clinical application. - Highlights: • Recent in vitro and in vivo results for DNA cleavage enzymes targeting persistent viral infections. • Analysis of the best animal models for testing enzymes for HBV, HSV, HIV and HPV. • Challenges facing in vivo delivery of therapeutic enzymes for persistent viral infections. • Safety issues to be addressed with proper animal studies.

  7. Persistence of viral RNA in the brain of experimentally infected mice with coxsackievirus B5

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    Sobotova Z.

    2011-04-01

    Full Text Available The aim of our study was to follow the persistence of viral RNA in selected organs of experimentally infected with coxsackievirus (CV B5 strains from different sources such as a patient’s sample, an environmental sample and a prototype virus strain. Methods . CD-1 mice were infected with CVB5 strain Faulkner the prototype, CVB5 – isolate from treated sewage waste and isolate from patient’s stool sample both identified as CVB5. The viral RNA was detected by RT-PCR using enterovirus primers specific for the non-coding 5' region. Results . We observed presence of RNA in the brain and heart of mice infected with isolate from patient’s stool at day 45 post infection (p. i.. Conclusion. We conclude that CVB5 persists in the brain and heart after oral infection of CD1 mice. The relevance of viral persistence maybe related viral origin and the genetics

  8. Viral (hepatitis C virus, hepatitis B virus, HIV) persistence and immune homeostasis.

    Science.gov (United States)

    Zhou, Yun; Zhang, Ying; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhan S

    2014-11-01

    Immune homeostasis is a host characteristic that maintains biological balance within a host. Humans have evolved many host defence mechanisms that ensure the survival of individuals upon encountering a pathogenic infection, with recovery or persistence from a viral infection being determined by both viral factors and host immunity. Chronic viral infections, such as hepatitis B virus, hepatitis C virus and HIV, often result in chronic fluctuating viraemia in the face of host cellular and humoral immune responses, which are dysregulated by multi-faceted mechanisms that are incompletely understood. This review attempts to illuminate the mechanisms involved in this process, focusing on immune homeostasis in the setting of persistent viral infection from the aspects of host defence mechanism, including interferon-stimulated genes, apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3), autophagy and interactions of various immune cells, cytokines and regulatory molecules. © 2014 John Wiley & Sons Ltd.

  9. IMBALANCE OF IMMUNOREGULATORY Th1- AND Th2-CYTOKINES IN PERSISTENT VIRAL INFECTIONS

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    I. O. Naslednikova

    2007-01-01

    Full Text Available Abstract. The article is considering certain features of immunopathogenesis exhibited in persistent viral infections, taking into account modern data and recently introduced immunological techniques. It has been revealed that a long-term persistence of hepatitis B and C viruses, tick-borne encephalitis, and herpes simplex is accompanied by deficient functioning in the T-cell compartment of immune system, and by markedly altered production of immunoregulatory cytokines in peripheral blood mononuclear leukocytes, mainly characterized by Th2 predominance.

  10. The effects of exposure of susceptible alpacas to alpacas persistently infected with bovine viral diarrhea virus

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    Reports of bovine viral diarrhea virus (BVDV) infections in alpacas have been increasing over the past several years but much is still unknown about the mechanisms of disease in this species. This report describes research performed to characterize the transmission of BVDV from persistently infected...

  11. Foxp3+ regulatory T cells control persistence of viral CNS infection.

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    Dajana Reuter

    Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

  12. Persistence of viral RNA in the brain of experimentally infected mice with coxsackievirus B5

    OpenAIRE

    Sobotova Z.; Marosova L.; Badurova M.; Sojka M.; Borsanyiova M.; Stipalova D.; Bopegamage S.

    2011-01-01

    The aim of our study was to follow the persistence of viral RNA in selected organs of experimentally infected with coxsackievirus (CV) B5 strains from different sources such as a patient’s sample, an environmental sample and a prototype virus strain. Methods . CD-1 mice were infected with CVB5 strain Faulkner the prototype, CVB5 – isolate from treated sewage waste and isolate from patient’s stool sample both identified as CVB5. The viral RNA was detected by RT-PCR using enterovirus primers sp...

  13. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

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    Gang Xin

    2015-11-01

    Full Text Available Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue “unhelped” CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells “help” the CD8 response during chronic infection via IL-21-induced BATF expression.

  14. Complexities in Isolation and Purification of Multiple Viruses from Mixed Viral Infections: Viral Interference, Persistence and Exclusion.

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    Naveen Kumar

    Full Text Available Successful purification of multiple viruses from mixed infections remains a challenge. In this study, we investigated peste des petits ruminants virus (PPRV and foot-and-mouth disease virus (FMDV mixed infection in goats. Rather than in a single cell type, cytopathic effect (CPE of the virus was observed in cocultured Vero/BHK-21 cells at 6th blind passage (BP. PPRV, but not FMDV could be purified from the virus mixture by plaque assay. Viral RNA (mixture transfection in BHK-21 cells produced FMDV but not PPRV virions, a strategy which we have successfully employed for the first time to eliminate the negative-stranded RNA virus from the virus mixture. FMDV phenotypes, such as replication competent but noncytolytic, cytolytic but defective in plaque formation and, cytolytic but defective in both plaque formation and standard FMDV genome were observed respectively, at passage level BP8, BP15 and BP19 and hence complicated virus isolation in the cell culture system. Mixed infection was not found to induce any significant antigenic and genetic diversity in both PPRV and FMDV. Further, we for the first time demonstrated the viral interference between PPRV and FMDV. Prior transfection of PPRV RNA, but not Newcastle disease virus (NDV and rotavirus RNA resulted in reduced FMDV replication in BHK-21 cells suggesting that the PPRV RNA-induced interference was specifically directed against FMDV. On long-term coinfection of some acute pathogenic viruses (all possible combinations of PPRV, FMDV, NDV and buffalopox virus in Vero cells, in most cases, one of the coinfecting viruses was excluded at passage level 5 suggesting that the long-term coinfection may modify viral persistence. To the best of our knowledge, this is the first documented evidence describing a natural mixed infection of FMDV and PPRV. The study not only provides simple and reliable methodologies for isolation and purification of two epidemiologically and economically important groups of

  15. Comprehensive analysis of LANA interacting proteins essential for viral genome tethering and persistence.

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    Subhash C Verma

    Full Text Available Kaposi's sarcoma associated herpesvirus is tightly linked to multiple human malignancies including Kaposi's sarcoma (KS, Primary Effusion Lymphoma (PEL and Multicentric Castleman's Disease (MCD. KSHV like other herpesviruses establishes life-long latency in the infected host by persisting as chromatin and tethering to host chromatin through the virally encoded protein Latency Associated Nuclear Antigen (LANA. LANA, a multifunctional protein, is capable of binding to a large number of cellular proteins responsible for transcriptional regulation of various cellular and viral pathways involved in blocking cell death and promoting cell proliferation. This leads to enhanced cell division and replication of the viral genome, which segregates faithfully in the dividing tumor cells. The mechanism of genome segregation is well known and the binding of LANA to nucleosomal proteins, throughout the cell cycle, suggests that these interactions play an important role in efficient segregation. Various biochemical methods have identified a large number of LANA binding proteins, including histone H2A/H2B, histone H1, MeCP2, DEK, CENP-F, NuMA, Bub1, HP-1, and Brd4. These nucleosomal proteins may have various functions in tethering of the viral genome during specific phases of the viral life cycle. Therefore, we performed a comprehensive analysis of their interaction with LANA using a number of different assays. We show that LANA binds to core nucleosomal histones and also associates with other host chromatin proteins including histone H1 and high mobility group proteins (HMGs. We used various biochemical assays including co-immunoprecipitation and in-vivo localization by split GFP and fluorescence resonance energy transfer (FRET to demonstrate their association.

  16. 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.

  17. Late Persistent Positive EBV Viral Load and Risk of Solid Cancer in Kidney Transplant Patients.

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    Bamoulid, Jamal; Courivaud, Cécile; Coaquette, Alain; Crépin, Thomas; Carron, Clémence; Gaiffe, Emilie; Roubiou, Caroline; Rebibou, Jean-Michel; Ducloux, Didier

    2017-06-01

    Recent studies reported that posttransplant Epstein-Barr virus (EBV) replication is frequent and indicates overimmunosuppression. We hypothesized that long-term EBV replication may identify overimmunosuppressed patients at higher risk of cancer. We analyzed a prospective cohort of renal transplant recipients having routine EBV PCR surveillance. All cancers (except EBV-related neoplasia) were recorded. Mean follow up was 94 + 23 months. Samples (8412) were available in 669 patients. Three hundred eighty-eight of the 669 patients (58%) had at least 1 positive viremia during follow-up.Epstein-Barr virus D+/R- patients (P = 0.046) as well as those having received antithymocyte globulin (P EBV viremia. Eighty-six patients (12.9%) developed a cancer during follow-up. The cumulated incidence of cancer was higher in patients with persistent high EBV replication (22.4% vs 10.2%, P = 0.005). The effect of persistent EBV infection remained significant even after adjustment for all confounding factors (hazard ratio, 1.69; 95% confidence interval, 1.10-2.61; P = 0.018). Age, history of antithymocyte globulin use, smoking, and history of cancer were also associated with cancer occurrence. Persistent high EBV viral load is associated with the occurrence of solid cancer. In this setting, more intensive screening and/or minimization of immunosuppressive treatment are probably required.

  18. Porcine epidemic diarrhea virus (PEDV) co-infection induced chlamydial persistence/stress does not require viral replication.

    Science.gov (United States)

    Schoborg, Robert V; Borel, Nicole

    2014-01-01

    Chlamydiae may exist at the site of infection in an alternative replicative form, called the aberrant body (AB). ABs are produced during a viable but non-infectious developmental state termed "persistence" or "chlamydial stress." As persistent/stressed chlamydiae: (i) may contribute to chronic inflammation observed in diseases like trachoma; and (ii) are more resistant to current anti-chlamydial drugs of choice, it is critical to better understand this developmental stage. We previously demonstrated that porcine epidemic diarrhea virus (PEDV) co-infection induced Chlamydia pecorum persistence/stress in culture. One critical characteristic of persistence/stress is that the chlamydiae remain viable and can reenter the normal developmental cycle when the stressor is removed. Thus, we hypothesized that PEDV-induced persistence would be reversible if viral replication was inhibited. Therefore, we performed time course experiments in which Vero cells were C. pecorum/PEDV infected in the presence of cycloheximide (CHX), which inhibits viral but not chlamydial protein synthesis. CHX-exposure inhibited PEDV replication, but did not inhibit induction of C. pecorum persistence at 24 h post-PEDV infection, as indicated by AB formation and reduced production of infectious EBs. Interestingly, production of infectious EBs resumed when CHX-exposed, co-infected cells were incubated 48-72 h post-PEDV co-infection. These data demonstrate that PEDV co-infection-induced chlamydial persistence/stress is reversible and suggest that this induction (i) does not require viral replication in host cells; and (ii) does not require de novo host or viral protein synthesis. These data also suggest that viral binding and/or entry may be required for this effect. Because the PEDV host cell receptor (CD13 or aminopeptidase N) stimulates cellular signaling pathways in the absence of PEDV infection, we suspect that PEDV co-infection might alter CD13 function and induce the chlamydiae to enter the

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

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    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.

  20. Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and viral persistence.

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    Chia, J; Chia, A; Voeller, M; Lee, T; Chang, R

    2010-02-01

    Enteroviruses are well-known causes of acute respiratory and/or gastrointestinal infections and non-specific flu-like illness. Although enterovirus protein, RNA and non-cytopathic viruses have been demonstrated in the stomach biopsies of patients with myalgia encephalomyelitis/chronic fatigue syndrome (ME/CFS), causality for chronic diseases is difficult to establish without having well-documented cases of acute enterovirus infections. The aim of this study was to link acute enteroviral infection to viral persistence in patients with ME/CFS. Patients admitted to the hospital with acute febrile illnesses were screened for enteroviral infections. Acutely infected patients were followed longitudinally, and those who developed symptoms of ME/CFS underwent oesophagogastroduodenoscopy and biopsies of the antrum to document viral persistence by immunoperoxidase staining for viral protein and viral RNA assay. Three representative patients with different manifestations of acute enterovirus infections progressed to have chronic symptoms of ME/CFS. Persistent viral infection was demonstrated in the antrum years later. After acute infections, enteroviruses can persist in patients resulting in manifestation of ME/CFS. Chronic enterovirus infection in an immunocompetent host may be an example of a stalemate between attenuated, intracellular viruses and an ineffective immune response.

  1. Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues.

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    Alec J Hirsch

    2017-03-01

    Full Text Available Zika virus (ZIKV, an emerging flavivirus, has recently spread explosively through the Western hemisphere. In addition to symptoms including fever, rash, arthralgia, and conjunctivitis, ZIKV infection of pregnant women can cause microcephaly and other developmental abnormalities in the fetus. We report herein the results of ZIKV infection of adult rhesus macaques. Following subcutaneous infection, animals developed transient plasma viremia and viruria from 1-7 days post infection (dpi that was accompanied by the development of a rash, fever and conjunctivitis. Animals produced a robust adaptive immune response to ZIKV, although systemic cytokine response was minimal. At 7 dpi, virus was detected in peripheral nervous tissue, multiple lymphoid tissues, joints, and the uterus of the necropsied animals. Notably, viral RNA persisted in neuronal, lymphoid and joint/muscle tissues and the male and female reproductive tissues through 28 to 35 dpi. The tropism and persistence of ZIKV in the peripheral nerves and reproductive tract may provide a mechanism of subsequent neuropathogenesis and sexual transmission.

  2. Tobacco Use and Sustained Viral Suppression in Youth Living with HIV.

    Science.gov (United States)

    Gamarel, Kristi E; Westfall, Andrew O; Lally, Michelle A; Hosek, Sybil; Wilson, Craig M

    2017-09-26

    Tobacco has been associated with worse HIV disease progression in adult samples of people living with HIV; however, studies have yet to examine these effects in youth living with HIV (YLWH). This study examined the association between tobacco smoking behaviors and sustained viral suppression among a sample of 820 YLWH who were recruited through the Adolescent Medicine Trials Network for HIV Interventions. Participants completed a cross-sectional survey and then staff abstracted viral suppression data from medical records for up to 26 weeks prior to enrollment. Overall, 20.4% of youth reported daily or almost daily tobacco use. In multivariable analyses, older age and daily or almost daily tobacco smoking, and ART adherence remained statistically significant in predicting sustained viral suppression over the study period. These findings underscore the need for tobacco screening and interventions in HIV care settings in order to identify youth in need of additional smoking cessation services.

  3. Sustainable HIV treatment in Africa through viral-load-informed differentiated care

    DEFF Research Database (Denmark)

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara

    2015-01-01

    every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load...... to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay...... in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost...

  4. Anal HPV 16 and 18 viral load: A comparison between HIV-negative and -positive MSM and association with persistence

    NARCIS (Netherlands)

    Marra, Elske; King, Audrey; van Logchem, Elske; van der Weele, Pascal; Mooij, Sofie H.; Heijman, Titia; Meijer, Chris J. L. M.; Verhagen, Dominique W. M.; van der Sande, Marianne A. B.; Schim van der Loeff, Maarten F.

    2018-01-01

    Does anal HPV viral load explain the difference in anal HPV persistence between HIV-negative and -positive men who have sex with men (MSM)? MSM 18 years were recruited in Amsterdam, the Netherlands, in 2010-2011. Anal self-swabs were collected every 6 months and genotyped

  5. Implementation of immunohistochemistry on frozen ear notch tissue samples in diagnosis of bovine viral diarrhea virus in persistently infected cattle.

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    Bedeković, Tomislav; Lemo, Nina; Lojkić, Ivana; Beck, Ana; Lojkić, Mirko; Madić, Josip

    2011-12-05

    Bovine viral diarrhea is a contagious disease of domestic and wild ruminants and one of the most economically important diseases in cattle. Bovine viral diarrhea virus belongs to the genus Pestivirus, within the family Flaviviridae. The identification and elimination of the persistently infected animals from herds is the initial step in the control and eradication programs. It is therefore necessary to have reliable methods for diagnosis of bovine viral diarrhea virus. One of those methods is immunohistochemistry. Immunohistochemistry on formalin fixed, paraffin embedded tissue is a routine technique in diagnosis of persistently infected cattle from ear notch tissue samples. However, such technique is inappropriate due to complicated tissue fixation process and it requires more days for preparation. On the contrary, immunohistochemistry on frozen tissue was usually applied on organs from dead animals. In this paper, for the first time, the imunohistochemistry on frozen ear notch tissue samples was described. Seventeen ear notch tissue samples were obtained during the period 2008-2009 from persistently infected cattle. Samples were fixed in liquid nitrogen and stored on -20°C until testing. Ear notch tissue samples from all persistently infected cattle showed positive results with good section quality and possibility to determinate type of infected cells. Although the number of samples was limited, this study indicated that immunohistochemistry on formalin fixed paraffin embedded tissue can be successfully replaced with immunohistochemistry on frozen ear notch tissue samples in diagnosis of persistently infected cattle.

  6. Implementation of immunohistochemistry on frozen ear notch tissue samples in diagnosis of bovine viral diarrhea virus in persistently infected cattle

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    Bedeković Tomislav

    2011-12-01

    Full Text Available Abstract Background Bovine viral diarrhea is a contagious disease of domestic and wild ruminants and one of the most economically important diseases in cattle. Bovine viral diarrhea virus belongs to the genus Pestivirus, within the family Flaviviridae. The identification and elimination of the persistently infected animals from herds is the initial step in the control and eradication programs. It is therefore necessary to have reliable methods for diagnosis of bovine viral diarrhea virus. One of those methods is immunohistochemistry. Immunohistochemistry on formalin fixed, paraffin embedded tissue is a routine technique in diagnosis of persistently infected cattle from ear notch tissue samples. However, such technique is inappropriate due to complicated tissue fixation process and it requires more days for preparation. On the contrary, immunohistochemistry on frozen tissue was usually applied on organs from dead animals. In this paper, for the first time, the imunohistochemistry on frozen ear notch tissue samples was described. Findings Seventeen ear notch tissue samples were obtained during the period 2008-2009 from persistently infected cattle. Samples were fixed in liquid nitrogen and stored on -20°C until testing. Ear notch tissue samples from all persistently infected cattle showed positive results with good section quality and possibility to determinate type of infected cells. Conclusions Although the number of samples was limited, this study indicated that immunohistochemistry on formalin fixed paraffin embedded tissue can be successfully replaced with immunohistochemistry on frozen ear notch tissue samples in diagnosis of persistently infected cattle.

  7. [Vaccination against viral hepatitis A and B in adults aged over 40 years--antibody persistence and immune memory].

    Science.gov (United States)

    Chlibek, R; Smetana, J; Bostíková, V; Splino, M

    2011-09-01

    Primary vaccination with combined vaccine against viral hepatitis A (VHA) and viral hepatitis B (VHB) induces higher anti-hepatitis B surface (anti-HBs) antibody responses and similar anti-hepatitis A virus (anti-HAV) antibody responses in adults aged over 40 years in comparison with concomitant monovalent vaccines against VHA and VHB. Th e objectives were to assess, in a clinical study, persistence of anti-HAV and anti-HBs antibodies in adults aged over 40 years four years after primary VHA/VHB vaccination and antibody response following a booster dose of the vaccine. Five hundred and ninety-six subjects aged > 40 years were vaccinated with three doses of the combined VHA/VHB vaccine at Months 0, 1, 6 (HAB group) or with concomitant VHA and VHB vaccines at Months 0, 6 and 0, 1, 6 (ENG+HAV and HBVX+VAQ, respectively). Blood samples were collected one month following primary vaccination (Month 7) and then at one-year intervals for four years after the booster dose with the same vaccine as used for the primary vaccination. The anti-HBs and anti-HAV antibody levels were determined prior to the booster dose and at days 14 and 30 after the booster dose. At Month 7, > 97% of study subjects were seropositive for anti-HAV antibodies in all groups analyzed. Four years after primary vaccination, anti-HAV antibody seropositivity persisted in > 93% of study subjects, increasing to > 99% after the booster dose. At Month 7, the highest proportion of study subjects with anti-HBs antibody levels > or = 10 mIU/ml was found in the HAB group (91.7% versus 79.7% in the ENG+HAV group versus 71.0% in the HBVX+VAQ group). Four years after vaccination, anti-HBs antibody levels of 10 mIU/ml persisted in 57.1% of the HAB study subjects in comparison with 40.1% and 26.6% of the study subjects in the ENG+HAV and HBVX+VAQ groups, respectively. One month after the booster dose, anti-HBs antibody levels increased and antibody levels > or = 10 mIU/ml was achived in 95.2% of study subjects in the

  8. Viral persistence, latent reservoir, and blips: a review on HIV-1 dynamics and modeling during HAART and related treatment implications

    Energy Technology Data Exchange (ETDEWEB)

    Rong, Libin [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

    2008-01-01

    HIV-1 eradication from infected individuals has not been achieved with the use of highly active antiretroviral therapy (HAART) for a prolonged period of time. The cellular reservoir for HIV-1 in resting memory CD4{sup +} T cells remains a major obstacle to viral elimination. The reservoir does not decay significantly over long periods of time as is able to release replication competent HIV-1 upon cell activation. Residual ongoing viral replication may likely occur in many patients because low levels of virus can be detected in plasma by sensitive assays and transient episodes of viremia, or HIV-1 blips, are often observed in patients even with successful viral suppression for many years. Here we review our current knowledge of the factors contributing to viral persistence, the latent reservoir, and blips, and mathematical models developed to explore them and their relationships. We show how mathematical modeling can help improve our understanding of HIV-1 dynamics in patients on HAART and the quantitative events underlying HIV-1 latency, reservoir stability, low-level viremic persistence, and emergence of intermittent viral blips. We also discuss treatment implications related to these studies.

  9. Sustainable HIV Treatment in Africa through Viral Load-Informed Differentiated Care

    Science.gov (United States)

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara; Cohn, Jennifer; Roberts, Teri; Ellman, Tom; Bonner, Kimberly; Rousseau, Christine; Garnett, Geoff; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Bansi-Matharu, Loveleen; Miners, Alec; Lundgren, Jens; Eaton, Jeff; Parkes-Ratanshi, Rosalind; Katz, Zachary; Maman, David; Ford, Nathan; Vitoria, Marco; Doherty, Meg; Dowdy, David; Nichols, Brooke; Murtagh, Maurine; Wareham, Meghan; Palamountain, Kara; Musanhu, Christine Chiedza; Stevens, Wendy; Katzenstein, David; Ciaranello, Andrea; Barnabas, Ruanne; Braithwaite, Scott; Bendavid, Eran; Nathoo, Kusum J; van de Vijver, David; Wilson, David; Holmes, Charles; Bershteyn, Anna; Walker, Simon; Raizes, Elliot; Jani, Ilesh; Nelson, Lisa; Peeling, Rosanna; Terris-Prestholt, Fern; Murungu, Joseph; Mutasa-Apollo, Tsitsi; Hallett, Timothy; Revill, Paul

    2016-01-01

    There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy (ART) in sub-Saharan Africa. Patients typically attend clinics every 1–3 months for clinical assessment, with clinic costs being comparable with costs of drugs themselves, CD4 counts are measured every 6 months, yet patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes a transition to more cost-effective ART deliver is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (“viral load”) provides a direct measure of current treatment effect. Viral load informed differentiated care is a means of tailoring care whereby those with suppressed viral load have less frequent clinical visits and attention is paid to those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach in many countries to measure viral load is by collecting dried blood spot (DBS) samples for testing in regional laboratories, although there have been concerns over the sensitivity/specificity of DBS to define treatment failure and the delay in receiving results. We use modelling to synthesize available evidence and evaluate the cost-effectiveness of viral load-informed differentiated care, account for limitations of DBS. We find that viral load-informed differentiated care using DBS is expected to be cost-effective and is recommended as the strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of future availability of point-of-care (POC) viral load tests. PMID:26633768

  10. Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence.

    Directory of Open Access Journals (Sweden)

    Cameron R Cunningham

    2016-01-01

    Full Text Available Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections.

  11. Overview on HTLV-I p12, p8, p30, p13: accomplices in persistent infection and viral pathogenesis.

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    Christophe eNicot

    2012-12-01

    Full Text Available The human T-lymphotropic virus type-1 (HTLV-1 is etiologically linked to adult T-cell leukemia/lymphoma (ATLL and tropical spastic paraparesis/ HTLV-1 associated myelopathy (TSP/HAM. While the role of Tax and Rex in viral replication and pathogenesis has been extensively studied, recent evidence suggests that additional viral proteins are essential for the virus life cycle in vivo. In this review, we will summarize possible molecular mechanisms evoked in the literature to explain how p12, p8, p30 and p13 facilitate persistent viral infection of the host. We will explore several stratagems used by HTLV-I accessory genes to escape immune surveillance, to establish latency and to deregulate cell cycle and apoptosis to participate in virus-mediated cellular transformation.

  12. Overview on HTLV-1 p12, p8, p30, p13: accomplices in persistent infection and viral pathogenesis.

    Science.gov (United States)

    Bai, Xue Tao; Nicot, Christophe

    2012-01-01

    The human T-lymphotropic virus type-1 (HTLV-1) is etiologically linked to adult T cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-1-associated myelopathy. While the role of Tax and Rex in viral replication and pathogenesis has been extensively studied, recent evidence suggests that additional viral proteins are essential for the virus life cycle in vivo. In this review, we will summarize possible molecular mechanisms evoked in the literature to explain how p12, p8, p30, and p13 facilitate persistent viral infection of the host. We will explore several stratagems used by HTLV-1 accessory genes to escape immune surveillance, to establish latency, and to deregulate cell cycle and apoptosis to participate in virus-mediated cellular transformation.

  13. Broad and persistent Gag-specific CD8+ T-cell responses are associated with viral control but rarely drive viral escape during primary HIV-1 infection

    Science.gov (United States)

    Radebe, Mopo; Gounder, Kamini; Mokgoro, Mammekwa; Ndhlovu, Zaza M.; Mncube, Zenele; Mkhize, Lungile; van der Stok, Mary; Jaggernath, Manjeetha; Walker, Bruce D.; Ndung’u, Thumbi

    2015-01-01

    Objective We characterized protein-specific CD8+ T-cell immunodominance patterns during the first year of HIV-1 infection, and their impact on viral evolution and immune control. Methods We analyzed CD8+ T-cell responses to the full HIV-1 proteome during the first year of infection in eighteen antiretroviral-naïve individuals with acute HIV-1 subtype C infection, all identified prior to seroconversion. Ex vivo and cultured IFN-γ ELISPOT assays were performed and viruses from plasma were sequenced within defined CTL Gag epitopes. Results Nef-specific CD8+ T-cell responses were dominant during the first 4 weeks post infection and made up 40% of total responses at this time, yet by 1 year responses against this region had declined and Gag responses made up to 47% of all T-cell responses measured. An inverse correlation between the breadth of Gag-specific responses and viral load set point was evident at 26 weeks post infection (p=0.0081; r= −0.60) and beyond. An inverse correlation between the number of persistent responses targeting Gag and viral set point was also identified (p=0.01; r=−0.58). Gag-specific responses detectable by the cultured ELISPOT assay correlated negatively with viral load set point (p=0.0013; r=−0.91). Sequence evolution in targeted and non-targeted Gag epitopes in this cohort was infrequent. Conclusions These data underscore the importance of HIV-specific CD8+ T-cell responses, particularly to the Gag protein, in the maintenance of low viral load levels during primary infection and show that these responses are initially poorly elicited by natural infection. These data have implications for vaccine design strategies. PMID:25387316

  14. [The role of persistent viral infections with Herpes viridae and Papilloma viridae associated with chronic inflammatory pathology of the oropharynx].

    Science.gov (United States)

    Yushchuk, N D; Kryukov, A I; Turovsky, A B; Popova, I A; Savostikova, M V

    The high prevalence of chronic inflammatory oropharyngeal pathologies and a large variety of specific pathogenetic features of the persistent viral infections caused by the species of the families Herpesviridae and Papillomaviridae as etiological agents of the disease suggest the necessity of investigations with a view to evaluating the clinical significance of persistent viral infections with Herpesviridae and Papillomaviridae species in the patients presenting with chronic inflammatory oropharyngreal pathology. The objective of the present study was to elucidate the prevalence and clinical significance of viral infections caused by the pathogenic agents belonging to the families Herpesviridae and Papillomaviridae in the patients presenting with chronic inflammatory pathology of the oropharynx. We examined two groups of patients one of which was comprised of 174 subjects suffering from chronic inflammatory oropharyngeal pathologies while the other consisted of 31 healthy people. All the patients in both groups underwent the general clinical examination, real-time PCR diagnostics of the viral infections with Herpes viridae and Papilloma viridae using the scrapings of oropharyngeal mucosa, and the microbiological study of the oropharynx secretion. The study has demonstrated the high frequency of viral infections caused by Herpesviridae and Papillomaviridae species in the patients with chronic inflammatory pathology of the oropharynx in comparison with the control group of healthy subjects (81.03% and 45.16% respectively). It was shown that the certain types of pathological conditions were specifically associated with the concrete forms of viral infections. The results of the cytological study give evidence that all (100%) the patients with chronic inflammatory oropharyngeal pathologies had the specific changes in epithelium in the combination with the non-specific alterations. 63.6% of the patients with chronic inflammatory oropharyngeal pathologies and negative

  15. Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity.

    Science.gov (United States)

    Pingen, Marieke; Wensing, Annemarie M J; Fransen, Katrien; De Bel, Annelies; de Jong, Dorien; Hoepelman, Andy I M; Magiorkinis, Emmanouil; Paraskevis, Dimitrios; Lunar, Maja M; Poljak, Mario; Nijhuis, Monique; Boucher, Charles A B

    2014-11-29

    In approximately 10% of newly diagnosed individuals in Europe, HIV-1 variants harboring transmitted drug resistance mutations (TDRM) are detected. For some TDRM it has been shown that they revert to wild type while other mutations persist in the absence of therapy. To understand the mechanisms explaining persistence we investigated the in vivo evolution of frequently transmitted HIV-1 variants and their impact on in vitro replicative capacity. We selected 31 individuals infected with HIV-1 harboring frequently observed TDRM such as M41L or K103N in reverse transcriptase (RT) or M46L in protease. In all these samples, polymorphisms at non-TDRM positions were present at baseline (median protease: 5, RT: 6). Extensive analysis of viral evolution of protease and RT demonstrated that the majority of TDRM (51/55) persisted for at least a year and even up to eight years in the plasma. During follow-up only limited selection of additional polymorphisms was observed (median: 1).To investigate the impact of frequently observed TDRM on the replication capacity, mutant viruses were constructed with the most frequently encountered TDRM as site-directed mutants in the genetic background of the lab strain HXB2. In addition, viruses containing patient-derived protease or RT harboring similar TDRM were made. The replicative capacity of all viral variants was determined by infecting peripheral blood mononuclear cells and subsequently monitoring virus replication. The majority of site-directed mutations (M46I/M46L in protease and M41L, M41L + T215Y and K103N in RT) decreased viral replicative capacity; only protease mutation L90M did not hamper viral replication. Interestingly, most patient-derived viruses had a higher in vitro replicative capacity than the corresponding site-directed mutant viruses. We demonstrate limited in vivo evolution of protease and RT harbouring frequently observed TDRM in the plasma. This is in line with the high in vitro replication capacity of patient

  16. Persistent Bovine Viral Diarrhea Virus infection in domestic and wild small ruminants and camelids including the mountain goat (Oreamnos americanus

    Directory of Open Access Journals (Sweden)

    Danielle Darracq Nelson

    2016-01-01

    Full Text Available Bovine viral diarrhea virus (BVDV is a Pestivirus best known for causing a variety of disease syndromes in cattle, including gastrointestinal disease, reproductive insufficiency, immunosuppression, mucosal disease, and hemorrhagic syndrome. The virus can be spread by transiently infected individuals and by persistently infected animals that may be asymptomatic while shedding large amounts of virus throughout their lifetime. BVDV has been reported in over 40 domestic and free-ranging species, and persistent infection has been described in eight of those species: white-tailed deer, mule deer, eland, mousedeer, mountain goats, alpacas, sheep, and domestic swine. This paper reviews the various aspects of BVDV transmission, disease syndromes, diagnosis, control, and prevention, as well as examines BVDV infection in domestic and wild small ruminants and camelids including mountain goats (Oreamnos americanus.

  17. Persistent Bovine Viral Diarrhea Virus Infection in Domestic and Wild Small Ruminants and Camelids Including the Mountain Goat (Oreamnos americanus).

    Science.gov (United States)

    Nelson, Danielle D; Duprau, Jennifer L; Wolff, Peregrine L; Evermann, James F

    2015-01-01

    Bovine viral diarrhea virus (BVDV) is a pestivirus best known for causing a variety of disease syndromes in cattle, including gastrointestinal disease, reproductive insufficiency, immunosuppression, mucosal disease, and hemorrhagic syndrome. The virus can be spread by transiently infected individuals and by persistently infected animals that may be asymptomatic while shedding large amounts of virus throughout their lifetime. BVDV has been reported in over 40 domestic and free-ranging species, and persistent infection has been described in eight of those species: white-tailed deer, mule deer, eland, mousedeer, mountain goats, alpacas, sheep, and domestic swine. This paper reviews the various aspects of BVDV transmission, disease syndromes, diagnosis, control, and prevention, as well as examines BVDV infection in domestic and wild small ruminants and camelids including mountain goats (Oreamnos americanus).

  18. Fatal Trichuris spp. infection in a Holstein heifer persistently infected with bovine viral diarrhea virus

    Science.gov (United States)

    2004-01-01

    Abstract Whipworms (Trichuris spp.) were identified in the colon of a recently purchased, 10-month-old dairy heifer that died suddenly. A skin test was positive for bovine viral diarrhea virus (BVDV). Signs of BVDV occurred in other heifers in the group, but fecal flotations were negative for whipworm eggs. PMID:15283522

  19. Economic costs associated with two testing strategies for screening feeder calves for persistent infection with bovine viral diarrhea virus.

    Science.gov (United States)

    Larson, Robert L; Miller, Robert B; Kleiboeker, Steve B; Miller, Margaret A; White, Brad J

    2005-01-15

    To develop partial budgets of the economic costs of 2 test strategies for screening cattle for persistent infection with bovine viral diarrhea virus (BVDV). Partial budget analysis. 938 calves arriving at 2 stocker operations. Calves were tested to determine prevalence of persistent BVDV infection. Test strategies that were evaluated included a single-test strategy consisting of immunohistochemical staining of skin biopsy specimens from all animals and a 2-test strategy consisting of polymerase chain reaction (PCR) assaying of pooled blood samples followed by immunohistochemical staining of skin biopsy specimens from animals in pools for which assay results were positive. Break-even costs (i.e., cost of persistent BVDV infection per animal necessary to justify whole-herd diagnostic testing) associated with each test strategy were calculated as a function of disease prevalence and test cost. Apparent prevalence of persistent BVDV infection was 0.32%. Sensitivity and specificity of the PCR assay for pooled samples were 100% and 89.7%, respectively. Regardless of the prevalence of persistent BVDV infection, the break-even cost for the 2-test strategy was lower than the break-even cost for the single-test strategy. However, the economic advantage was greatest when prevalence was low. Results suggest that using a 2-test strategy to screen cattle for persistent BVDV infection, whereby the first test involves PCR assaying of pooled samples and the second involves immunohistochemical testing only of those animals represented in pooled samples with positive assay results, will reduce the cost of screening incoming feedlot cattle, compared with immunohistochemical testing of all animals.

  20. Persistence of airway hyperresponsiveness and viral antigen following respiratory syncytial virus bronchiolitis in young guinea-pigs.

    Science.gov (United States)

    Riedel, F; Oberdieck, B; Streckert, H J; Philippou, S; Krusat, T; Marek, W

    1997-03-01

    Respiratory syncytial virus (RSV) bronchiolitis in infancy is known to be followed by chronic respiratory symptoms and airway hyperresponsiveness in a subgroup of patients. To further investigate the pathogenesis of RSV-induced chronic airway pathology, we infected young guinea-pigs at 4 weeks of age with RSV applied as an aerosol (n=30), and control guinea-pigs with virus-free culture medium (n=24). Infection was confirmed by positive antibody titre to RSV after 6 weeks, and by typical pathological changes of bronchiolitis after 1 week in six animals from each group. Airway hyperresponsiveness was measured weekly for 5 weeks by histamine challenge, using body-plethysmographic measurement of compressed air (CA). The provocative concentration of histamine producing significant airway obstruction (i.e. CA = 0.1 mL) (PC0.1 mL CA in mg x mL(-1)) was calculated from dose-response curves. Six weeks postinfection, the lungs were investigated for the presence of inflammation and of viral antigen by immunofluorescence and immunohistochemistry using a rabbit hyperimmune serum and monoclonal antibodies. Airway responsiveness was increased in the RSV group 1 week postinfection compared to the control group (PC0.1 mL CA median 2.50 vs >10 mg x mL(-1); p10 mg x mL(-1); p<0.001). During the same period, viral antigen persisted in the lungs of infected animals, although there was less inflammation at 6 weeks postinfection than at 1 week postinfection. In guinea-pigs, respiratory syncytial virus infection of the airways causes persistent airway hyperresponsiveness over a period of at least 5 weeks. During this time, viral antigen, but not inflammation, remains detectable in the lungs and might be responsible for ongoing airway hyperresponsiveness.

  1. Clinical profile of Monomelic Amyotrophy (MMA) and role of persistent viral infection.

    Science.gov (United States)

    Vibha, Deepti; Behari, Madhuri; Goyal, Vinay; Shukla, Garima; Bhatia, Rohit; Srivastava, Achal Kumar; Vivekanandhan, S

    2015-12-15

    The objective of our study was to describe the clinical characteristics, electrophysiology, MRI features and conduct viral assays in patients with Monomelic Amyotrophy (MMA) and follow them up over one year. Consecutive patients with MMA who attended the Neurology services from April 2013 to March 2014 were included. Age and sex matched controls were taken for the purpose of viral assay analysis. The clinical evaluation was repeated at six months and one year. 109 cases and 109 controls were included in the study. The patients were predominantly males (98.2%; n=107/109) and had involvement of upper limbs (83.5%; n=91/109). 26 (23.8%) patients with clinically unilateral involvement had bilateral neurogenic changes in the electromyography. Serological assays of Japanese E, West Nile Virus, and Poliovirus 1, 2 and 3, HIV 1 and 2 were negative in all the cases and controls. Patients with MMA are predominantly young males with upper limb wasting and weakness. MRI of the cervical cord is normal in most of the patients (67.9%). The present study did not find any evidence of the association of viral infection in MMA. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds.

    Directory of Open Access Journals (Sweden)

    Wan-Lin Yang

    2015-03-01

    Full Text Available Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS. All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V to 2.7/100-person-years;[0.7, 10.9] (for 215D. RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs. When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.

  3. Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo.

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    Upkar S Gill

    2016-08-01

    Full Text Available NK cells are important antiviral effectors, highly enriched in the liver, with the potential to regulate immunopathogenesis in persistent viral infections. Here we examined whether changes in the NK pool are induced when patients with eAg-positive CHB are 'primed' with PegIFNα and importantly, whether these changes are sustained or further modulated long-term after switching to nucleos(tides (sequential NUC therapy, an approach currently tested in the clinic. Longitudinal sampling of a prospectively recruited cohort of patients with eAg+CHB showed that the cumulative expansion of CD56bright NK cells driven by 48-weeks of PegIFNα was maintained at higher than baseline levels throughout the subsequent 9 months of sequential NUCs. Unexpectedly, PegIFNα-expanded NK cells showed further augmentation in their expression of the activating NK cell receptors NKp30 and NKp46 during sequential NUCs. The expansion in proliferating, functional NK cells was more pronounced following sequential NUCs than in comparison cohorts of patients treated with de novo NUCs or PegIFNα only. Reduction in circulating HBsAg concentrations, a key goal in the path towards functional cure of CHB, was only achieved in those patients with enhancement of NK cell IFNγ and cytotoxicity but decrease in their expression of the death ligand TRAIL. In summary, we conclude that PegIFNα priming can expand a population of functional NK cells with an altered responsiveness to subsequent antiviral suppression by NUCs. Patients on sequential NUCs with a distinct NK cell profile show a decline in HBsAg, providing mechanistic insights for the further optimisation of treatment strategies to achieve sustained responses in CHB.

  4. HIV-associated neurodevelopmental delay: prevalence, predictors and persistence in relation to antiretroviral therapy initiation and viral suppression.

    Science.gov (United States)

    Strehlau, R; Kuhn, L; Abrams, E J; Coovadia, A

    2016-11-01

    HIV infection in infancy may influence the developing brain, leading to adverse neurodevelopmental consequences. We aim to describe neurodevelopmental characteristics of a cohort of HIV-infected infants and young children prior to antiretroviral therapy (ART) initiation and after achieving viral suppression. As part of the Neverest 2 trial, 195 HIV-infected children under 2 years of age were assessed using the Ages and Stages Questionnaire (ASQ) prior to ART initiation and at subsequent age-appropriate time points after ART had been started. The ASQ is a simple screening questionnaire used to identify children at risk of neurodevelopmental delays. Questionnaires completed by the parent/caregiver assess neurodevelopmental functioning in five domains: communication, gross motor, fine motor, problem solving and personal-social. Median age pre-ART was 8.8 months (range 2.2-24.9) and 53.9% were male. Mean time to viral suppression was 9.4 months (range 5.9-14.5). Compared with pre-ART better outcomes were reported at time of viral suppression with a lower proportion of children failing the gross motor (31.5% vs. 13%, p = 0.0002), fine motor (21.3% vs. 10.2%, p = 0.017), problem solving (26.9% vs. 9.3%, p = 0.0003) and personal-social (19.6% vs. 7.4%, p = 0.019) domains. However, there was no change in the communication domain (14.8% vs. 12.0%, p = 0.6072). Although achieving viral suppression on ART resulted in significant improvements in markers of neurodevelopmental function of young HIV-infected children, potential neurodevelopmental delays still persisted in a large proportion. Further interventions are needed to limit potential disabilities and maximize developmental outcomes. © 2016 John Wiley & Sons Ltd.

  5. Infected CD8α− dendritic cells are the predominant source of IL-10 during establishment of persistent viral infection

    Science.gov (United States)

    Ng, Cherie T.; Oldstone, Michael B. A.

    2012-01-01

    Interleukin-10 (IL-10) is an important factor involved in T-cell dysfunction during persistent viral infection. Although several factors can negatively regulate T-cell activity, targeting of the IL-10 pathway alone is sufficient to regenerate T-cell activity and increase viral control. How IL-10 mediates these effects is unclear. Here, we investigated the cellular source of IL-10 necessary for establishing T-cell exhaustion and viral persistence, using IL-10 reporter mice (VertX), cell-type–specific IL-10 and IL-10 receptor deletion mice, and bone marrow chimeric mice. During establishment of viral persistence, the cellular subset with the most prevalent expression of IL-10 was CD8α−CD4+ dendritic cells (DCs), which produced IL-10 with increasing kinetics until 9 d postinfection. After this time point, DCs exhibited a modest decline in percentage of IL-10+ cells whereas B cells and CD4+ T cells increased minimally. Further analysis of the DC population demonstrated that IL-10 was primarily expressed in infected DCs. These DCs were a notable source of IL-10 as mutant mice with a DC-specific deletion of IL-10 had significantly decreased serum levels. Interestingly, viral infection was not directly causative of IL-10 expression; rather, IL-10 production appeared to be linked to type I IFN signaling. Our findings further illuminate the contribution of DCs to the production of IL-10 and to viral persistence. PMID:22893686

  6. Prevalent and persistent viral infection in cultures of the coral algal endosymbiont Symbiodinium

    Science.gov (United States)

    Weynberg, Karen D.; Neave, Matthew; Clode, Peta L.; Voolstra, Christian R.; Brownlee, Christopher; Laffy, Patrick; Webster, Nicole S.; Levin, Rachel A.; Wood-Charlson, Elisha M.; van Oppen, Madeleine J. H.

    2017-09-01

    Reef corals are under threat from bleaching and disease outbreaks that target both the host animal and the algal symbionts within the coral holobiont. A viral origin for coral bleaching has been hypothesized, but direct evidence has remained elusive. Using a multifaceted approach incorporating flow cytometry, transmission electron microscopy, DNA and RNA virome sequencing, we show that type C1 Symbiodinium cultures host a nucleocytoplasmic large double-stranded DNA virus (NCLDV) related to Phycodnaviridae and Mimiviridae, a novel filamentous virus of unknown phylogenetic affiliation, and a single-stranded RNA virus related to retroviruses. We discuss implications of these findings for laboratory-based experiments using Symbiodinium cultures.

  7. Prevalent and persistent viral infection in cultures of the coral algal endosymbiont Symbiodinium

    KAUST Repository

    Weynberg, Karen D.

    2017-03-17

    Reef corals are under threat from bleaching and disease outbreaks that target both the host animal and the algal symbionts within the coral holobiont. A viral origin for coral bleaching has been hypothesized, but direct evidence has remained elusive. Using a multifaceted approach incorporating flow cytometry, transmission electron microscopy, DNA and RNA virome sequencing, we show that type C1 Symbiodinium cultures host a nucleocytoplasmic large double-stranded DNA virus (NCLDV) related to Phycodnaviridae and Mimiviridae, a novel filamentous virus of unknown phylogenetic affiliation, and a single-stranded RNA virus related to retroviruses. We discuss implications of these findings for laboratory-based experiments using Symbiodinium cultures.

  8. Synergistic effect of viral load and alcohol consumption on the risk of persistent high-risk human papillomavirus infection.

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    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.

  9. Viral transduction of renin rapidly establishes persistent hypertension in diverse murine strains.

    Science.gov (United States)

    Harlan, Shannon M; Ostroski, Robert A; Coskun, Tamer; Yantis, Loudon D; Breyer, Matthew D; Heuer, Josef G

    2015-09-01

    Mice provide a unique platform to dissect disease pathogenesis, with the availability of recombinant inbred strains and diverse genetically modified strains. Leveraging these reagents to elucidate the mechanisms of hypertensive tissue injury has been hindered by difficulty establishing persistent hypertension in these inbred lines. ANG II infusion provides relatively short-term activation of the renin-angiotensinogen system (RAS) with concomitant elevated arterial pressure. Longer-duration studies using renin transgenic mice are powerful models of chronic hypertension, yet are limited by the genetic background on which the transgene exists and the exposure throughout development. The present studies characterized hypertension produced by transduction with a renin-coding adeno-associated virus (ReninAAV). ReninAAV mice experienced elevated circulating renin with concurrent elevations in arterial pressure. Following a single injection of ReninAAV, arterial pressure increased on average +56 mmHg, an increase that persisted for at least 12 wk in three distinct and widely used strains of adult mice: 129/S6, C56BL/6, and DBA/2J. This was accomplished without surgical implantation of pumps or complex breeding and backcrossing. In addition, ReninAAV mice developed pathophysiological changes associated with chronic hypertension, including increased heart weight and albuminuria. Thus ReninAAV provides a unique tool to study the onset of and effects of persistent hypertension in diverse murine models. This model should facilitate our understanding of the pathogenesis of hypertensive injury. Copyright © 2015 the American Physiological Society.

  10. Bovine viral diarrhea virus fetal persistent infection after immunization with a contaminated modified-live virus vaccine.

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    Palomares, Roberto A; Marley, Shonda M; Givens, M Daniel; Gallardo, Rodrigo A; Brock, Kenny V

    2013-05-01

    The objective was to determine whether a multivalent modified-live virus vaccine containing noncytopathic bovine viral diarrhea virus (BVDV) administered off-label to pregnant cattle can result in persistently infected fetuses and to assess whether vaccinal strains can be shed to unvaccinated pregnant cattle commingling with vaccinates. Nineteen BVDV-naïve pregnant heifers were randomly assigned to two groups: cattle vaccinated near Day 77 of gestation with modified-live virus vaccine containing BVDV-1a (WRL strain), bovine herpes virus-1, parainfluenza 3, and bovine respiratory syncytial virus (Vx group; N = 10) or control unvaccinated cattle (N = 9). During the course of the study a voluntary stop-sale/recall was conducted by the manufacturer because of the presence of a BVDV contaminant in the vaccine. At Day 175 of gestation, fetuses were removed by Cesarean section and fetal tissues were submitted for virus isolation, and quantitative reverse transcription polymerase chain reaction using BVDV-1- and BVDV-2-specific probes. Nucleotide sequencing of viral RNA was performed for quantitative reverse transcription polymerase chain reaction-positive samples. Two vaccinated and two control heifers aborted their pregnancies, but their fetuses were unavailable for BVDV testing. Virus was isolated from all eight fetuses in the Vx group heifers and from 2 of 7 fetuses in the control unvaccinated heifers. Only BVDV-2 was detected in fetuses from the Vx group, and only BVDV-1 was detected in the two fetuses from the control group. Both BVDV-1 and BVDV-2 were detected in the vaccine. In conclusion, vaccination of pregnant heifers with a contaminated modified-live BVDV vaccine resulted in development of BVDV-2 persistently infected fetuses in all tested vaccinated animals. Furthermore, BVDV was apparently shed to unvaccinated heifers causing fetal infections from which only BVDV-1 was detected. Published by Elsevier Inc.

  11. Oral-tolerization Prevents Immune Responses and Improves Transgene Persistence Following Gene Transfer Mediated by Adeno-associated Viral Vector.

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    Hardet, Romain; Chevalier, Benjamin; Dupaty, Léa; Naïmi, Yassine; Riou, Gaëtan; Drouot, Laurent; Jean, Laetitia; Salvetti, Anna; Boyer, Olivier; Adriouch, Sahil

    2016-02-01

    Gene therapy represents a feasible strategy to treat inherited monogenic diseases and intramuscular (i.m.) injection of recombinant adeno-associated viral (AAV) vector is now recognized as a convenient and safe method of gene transfer. However, this approach is hampered by immune responses directed against the vector and against the transgenic protein. We used here to reproduce this situation a mouse model where robust immune responses are induced following injection of an AAV vector coding for an immunogenic transgenic protein. We show that prophylactic oral administration of the immunogenic protein before AAV-mediated gene transfer completely prevented antibody formation and cytotoxic CD8(+) T-cell response. Consistently, prophylactic oral-tolerization considerably improved long-term transgene persistence and expression. Mechanistically, inhibition of the cytotoxic immune response involved abortive proliferation of antigen-specific cytotoxic CD8(+) T cells, upregulation of the PD-1 immunoregulatory molecule, downregulation of the Bcl-2 antiapoptotic factor, and their deletion in the context of AAV-mediated gene transfer. Hence, gene therapy may represent an ideal situation where oral-tolerization can be adopted before or at the same time as vector injection to efficiently prevent deleterious immune responses directed against the transgenic protein.

  12. Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection

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    Larrubia, Juan R; Benito-Martínez, Selma; Calvino, Miryam; Sanz-de-Villalobos, Eduardo; Parra-Cid, Trinidad

    2008-01-01

    Chemokines produced in the liver during hepatitis C virus (HCV) infection induce migration of activated T cells from the periphery to infected parenchyma. The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper/T-cytotoxic type-1 cell (Th1/Tc1) response. These chemokines consist of CCL3 (macrophage inflammatory protein-1α; MIP-1α), CCL4 (MIP-1β), CCL5 (regulated on activation normal T cell expressed and secreted; RANTES), CXCL10 (interferon-γ−inducible protein-10; IP-10), CXCL11 (interferon-inducible T-cell α chemoattractant; I-TAC), and CXCL9 (monokine induced by interferon γ; Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors. Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C. The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection. When the adaptive immune response fails in this task, non-specific T cells without the capacity to control the infection are also recruited to the liver, and these are ultimately responsible for the persistent hepatic damage. The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection, and to maintain liver viability during the chronic phase, by impairing non-specific T cell migration. Some chemokines and their receptors correlate with liver damage, and CXCL10 (IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome. The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver. PMID:19084927

  13. Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy.

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    Tracy R Glass

    Full Text Available BACKGROUND: Good adherence to antiretroviral therapy (ART is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels. METHODS: Eligible individuals were Caucasians treated with efavirenz (EFV and/or boosted lopinavir (LPV/r with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6 and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2. Viral suppression was defined as having HIV-1 RNA 1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR 0.11, 95% confidence interval (CI: 0.01-0.99; LPV/r: OR 0.29, 95% CI: 0.09-0.94. In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62-18.75; LPV/r: OR 5.65, 95% CI: 1.82-17.56. CONCLUSIONS: The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.

  14. Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy.

    Science.gov (United States)

    Glass, Tracy R; Rotger, Margalida; Telenti, Amalio; Decosterd, Laurent; Csajka, Chantal; Bucher, Heiner C; Günthard, Huldrych F; Rickenbach, Martin; Nicca, Dunja; Hirschel, Bernard; Bernasconi, Enos; Wandeler, Gilles; Battegay, Manuel; Marzolini, Catia

    2012-01-01

    Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels. Eligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA 1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01-0.99; LPV/r: OR 0.29, 95% CI: 0.09-0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62-18.75; LPV/r: OR 5.65, 95% CI: 1.82-17.56). The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.

  15. Experimentally infected domestic ducks show efficient transmission of Indonesian H5N1 highly pathogenic avian influenza virus, but lack persistent viral shedding.

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    Hendra Wibawa

    Full Text Available Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15, which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2-8 dpi. Viral ribonucleic acid was detected from 1-15 days post inoculation from the oral route and 1-24 days post inoculation from the cloacal route (cycle threshold <40. Most ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks. However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10 and contact ducks (n = 9 when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5 than inoculation-infected ducks (1 of 15. We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection.

  16. CONTROL OF VIRAL DISEASES TRANSMITTED IN A PERSISTENT MANNER BY THRIPS IN PEPPER (TOMATO SPOTTED WILT VIRUS).

    Science.gov (United States)

    Fanigliulo, A; Viggiano, A; Gualco, A; Crescenzi, A

    2014-01-01

    Tomato spotted wilt disease is caused by Tomato Spotted Wilt Virus (TSWV) (Tospovirus, Bunyaviridae), a virus that severely damages and reduces the yield of many economically important plants worldwide and actually it is a major disease affecting the production of tomato and pepper in Italy. Due to the non-predictive nature of its outbreaks combined with the lack of forecasting, adoption of preventive measures have not always been practical, in fact the disease cycle has proven to be extremely difficult to break because of the wide and often overlapping host range of both the virus and the thrips vectors, which transmit the virus in a persistent, circulative, and propagative manner. Moreover recently, resistance breaking (RB) isolates of TSWV that overcome the resistance conferred by the Tsw gene in different pepper hybrids have been recovered in different locations in Italy and also in Brazil, USA, Spain and Australia, and this occurrence raises the question on the importance of a new approach of integrated pest management for TSWV management, including both control of its insect vector and the induction of the plant's resistance against viral infection. In this perspective, a study was performed in 2012 and 2013 with the purpose of evaluating the efficacy of the insecticide Cyantraniliprole alone or combined with Acibenzolar-S-Methyl (ASM), inducer of systemic acquired resistance, in the control of tomato spotted wilt disease in pepper. The experiment was performed in laboratory, in a thermo-conditioned greenhouse, into separate insect-proof cages and consisted of 5 treatments and 2 applications (plus a pre-transplant application for treatments were ASM was used. Variables were the mode of application of ASM in pre-transplant (by foliar or by drench) and the duration of the exposure time of the treated plants to viruliferous insects. Pepper cv. Corno di Toro, devoid of any resistance to TSWV, was used. Plants were observed daily to record any symptom induced by

  17. Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection

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    Laura M. Snell

    2016-09-01

    Full Text Available Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and persistent virus infection, demonstrating an unrecognized suppressive function for PD-L1 in virus infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control persistent viral infection.

  18. Stationary-Phase Persisters to Ofloxacin Sustain DNA Damage and Require Repair Systems Only during Recovery.

    Science.gov (United States)

    Völzing, Katherine G; Brynildsen, Mark P

    2015-09-01

    Chronic infections are a serious health care problem, and bacterial persisters have been implicated in infection reoccurrence. Progress toward finding antipersister therapies has been slow, in part because of knowledge gaps regarding the physiology of these rare phenotypic variants. Evidence shows that growth status is important for survival, as nongrowing cultures can have 100-fold more persisters than growing populations. However, additional factors are clearly important, as persisters remain rare even in nongrowing populations. What features, beyond growth inhibition, allow persisters to survive antibiotic stress while the majority of their kin succumb to it remains an open question. To investigate this, we used stationary phase as a model nongrowing environment to study Escherichia coli persistence to ofloxacin. Given that the prevailing model of persistence attributes survival to transient dormancy and antibiotic target inactivity, we anticipated that persisters would suffer less damage than their dying kin. However, using genetic mutants, flow cytometry, fluorescence-activated cell sorting, and persistence assays, we discovered that nongrowing ofloxacin persisters experience antibiotic-induced damage that is indistinguishable from that of nonpersisters. Consistent with this, we found that these persisters required DNA repair for survival and that repair machinery was unnecessary until the posttreatment recovery period (after ofloxacin removal). These findings suggest that persistence to ofloxacin is not engendered solely by reduced antibiotic target corruption, demonstrate that what happens following antibiotic stress can be critical to the persistence phenotype, and support the notion that inhibition of DNA damage repair systems could be an effective strategy to eliminate fluoroquinolone persisters. In the absence of resistant mutants, infection reoccurrences can still occur because of persisters, rare bacterial cells that survive antibiotic treatments to

  19. Slc15a4, a gene required for pDC sensing of TLR ligands, is required to control persistent viral infection.

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    Amanda L Blasius

    2012-09-01

    Full Text Available Plasmacytoid dendritic cells (pDCs are the major producers of type I IFN in response to viral infection and have been shown to direct both innate and adaptive immune responses in vitro. However, in vivo evidence for their role in viral infection is lacking. We evaluated the contribution of pDCs to acute and chronic virus infection using the feeble mouse model of pDC functional deficiency. We have previously demonstrated that feeble mice have a defect in TLR ligand sensing. Although pDCs were found to influence early cytokine secretion, they were not required for control of viremia in the acute phase of the infection. However, T cell priming was deficient in the absence of functional pDCs and the virus-specific immune response was hampered. Ultimately, infection persisted in feeble mice. We conclude that pDCs are likely required for efficient T cell priming and subsequent viral clearance. Our data suggest that reduced pDC functionality may lead to chronic infection.

  20. Increased regulatory T cells and impaired functions of circulating CD8 T lymphocytes is associated with viral persistence in Hepatitis B virus-positive newborns.

    Science.gov (United States)

    Shrivastava, S; TrehanPati, N; Patra, S; Kottilil, S; Pande, C; Trivedi, S S; Sarin, S K

    2013-08-01

    Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25-90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. CD8 T cells play a pivotal role in clearing the Hepatitis B virus infection in adults. Herein, we sought to delineate the role of T cells in viral persistence in HBsAg+ve newborns. At birth peripheral and cord blood of HBsAg+ve (N = 12), HBsAg-ve (N = 10) and healthy newborns (HC: N = 15) were evaluated for T-cell frequency and functionality by flow cytometry. No significant differences were observed in the frequency of CD8 and CD4 T cells in all the three groups. However, significantly higher frequency of FoxP3 expressing regulatory T cells were observed in HBsAg+ve (63.79%) compared with HBsAg-ve (28.12%) and HC (11.06%) (P functional defect in CD8 T cells by decreased IFN-γ production and lower CD107A expression (cytotoxic capacity) compared with HBsAg-ve and HC, which positively correlated with decreased TCRζ-chain expression CD8 T cells (r(2) > 0.93, P < 0.05). Despite equal frequency of CD8 T cells in all the three groups, CD8 T cells in HBsAg+ve newborns are dysfunctional. An expansion of regulatory T cells and impaired TCR signalling may represent the immune tolerant state of the adaptive immune system in response to chronic HBV infection. © 2013 John Wiley & Sons Ltd.

  1. Five-year follow-up of patients with chronic C hepatitis and sustained virological response Seguimiento a 5 años de pacientes con hepatitis crónica C y respuesta viral sostenida

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    I. Puig-del-Castillo

    2011-02-01

    Full Text Available Objective: to assess persistence of sustained viral response at 5 years of follow-up in patients with chronic viral hepatitis C treated with pegylated interferon and ribavirin. Design: a descriptive study. Patients: from August 2001 to May 2004, all patients treated at our center with pegylated interferon and ribavirin who achieved a sustained viral response were consecutively enrolled (93 patients. Demographic, histological, biochemical, and virological data were collected during treatment and 5 years after achievement of the sustained viral response. Eighty-six percent of patients enrolled (n = 80 attended the control visit at 5 years. Results: mean age of enrolled patients was 41 years (standard deviation = 10 years, and 30.1% (n = 28 were women. Liver biopsy had been performed before treatment in 68.8% of patients (n = 64, showing no or mild fibrosis in 62.3% (F0 and F1 and significant fibrosis and cirrhosis in 37.7% (F ≥ 3. Genotype distribution was: 58.1% genotype 1 (n = 54; 8.6% genotype 2 (n = 8; 24.7% genotype 3 (n = 23; 7.5% genotype 4 (n = 7, and indeterminate in one patient. Only one patient experienced virological recurrence. All other patients had negative HCV RNA levels and, in the absence of other liver diseases, normal ALT levels. Conclusion: in patients treated with pegylated interferon and ribavirin with sustained viral response, long-term recurrence rate was very low.Objetivo: evaluar la persistencia de respuesta viral sostenida a los 5 años de seguimiento en pacientes con hepatitis crónica por virus C tratados con interferón pegilado y ribavirina. Diseño: estudio descriptivo. Pacientes: desde agosto de 2001 hasta mayo de 2004, se incluyeron de forma consecutiva todos los pacientes de nuestro centro tratados con interferón pegilado y ribavirina que alcanzaron respuesta viral sostenida (93 pacientes. Se recogieron datos demográficos, histológicos, bioquímicos y virológicos durante el tratamiento y a los 5 años de

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

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    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.

  3. Infection expérimentale de veaux par le virus respiratoire syncytial bovin : évaluation de la persistance virale

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    Callendret, Benoît

    2002-01-01

    Le Virus Respiratoire Syncytial Bovin (VRSB) est une cause majeure de maladie respiratoire des jeunes bovins. La persistance du VRSB et du VRS humain à pu être démontrée in vitro sur différentes lignées cellulaires et in vivo sur des cobayes ou sur des sujets immunodéprimés. En revanche, la persistance du VRS in vivo chez son hôte naturel immunocompétent n'a jamais pu être mise en évidence. Elle a pourtant depuis longtemps été fortement suspectée à partir des données épidémiologiques. En outr...

  4. Protein X of Borna disease virus inhibits apoptosis and promotes viral persistence in the central nervous systems of newborn-infected rats.

    Science.gov (United States)

    Poenisch, Marion; Burger, Nils; Staeheli, Peter; Bauer, Georg; Schneider, Urs

    2009-05-01

    Borna disease virus (BDV) is a neurotropic member of the order Mononegavirales with noncytolytic replication and obligatory persistence in cultured cells and animals. Here we show that the accessory protein X of BDV represents the first mitochondrion-localized protein of an RNA virus that inhibits rather than promotes apoptosis induction. Rat C6 astroglioma cells persistently infected with wild-type BDV were significantly more resistant to death receptor-dependent and -independent apoptotic stimuli than uninfected cells or cells infected with a BDV mutant expressing reduced amounts of X. Confocal microscopy demonstrated that X colocalizes with mitochondria and expression of X from plasmid DNA rendered human 293T and mouse L929 cells resistant to apoptosis induction. A recombinant virus encoding a mutant X protein unable to associate with mitochondria (BDV-X(A6A7)) failed to block apoptosis in C6 cells. Furthermore, Lewis rats neonatally infected with BDV-X(A6A7) developed severe neurological symptoms and died around day 30 postinfection, whereas all animals infected with wild-type BDV remained healthy and became persistently infected. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining revealed a significant increase in the number of apoptotic cells in the brain of BDV-X(A6A7)-infected animals, whereas the numbers of CD3(+) T lymphocytes were comparable to those detected in animals infected with wild-type BDV. Our data thus indicate that inhibition of apoptosis by X promotes noncytolytic viral persistence and is required for the survival of cells in the central nervous system of BDV-infected animals.

  5. Decay of ccc-DNA marks persistence of intrahepatic viral DNA synthesis under tenofovir in HIV-HBV co-infected patients.

    Science.gov (United States)

    Boyd, Anders; Lacombe, Karine; Lavocat, Fabien; Maylin, Sarah; Miailhes, Patrick; Lascoux-Combe, Caroline; Delaugerre, Constance; Girard, Pierre-Marie; Zoulim, Fabien

    2016-10-01

    In the presence of highly-potent antivirals, persistence of hepatitis B virus (HBV) is most well-characterized by covalently-closed circular DNA (cccDNA) and total intrahepatic DNA (IH-DNA). We sought to determine how antiviral therapy could affect their levels during human immunodeficiency virus (HIV)-HBV co-infection. Sixty co-infected patients from a well-defined cohort with ⩾1 liver biopsy were studied. HBV cccDNA and total IH-DNA were extracted from biopsies and quantified by real-time PCR. Factors associated with intrahepatic viral load were determined using mixed-effect linear regression and half-life viral kinetics during reconstructed follow-up using non-linear exponential decay models. At biopsy, 35 (58.3%) patients were hepatitis B "e" antigen (HBeAg)-positive and 33 (55.0%) had detectable plasma HBV-DNA (median=4.58log10IU/ml, IQR=2.95-7.43). Overall, median cccDNA was -0.95log10copies/cell (IQR=-1.70, -0.17) and total IH-DNA was 0.27log10copies/cell (IQR=-0.39, 2.00). In multivariable analysis, significantly lower levels of cccDNA and total IH-DNA were observed in patients with HBeAg-negative serology, nadir CD4(+) cell counts >250/mm(3), and longer cumulative TDF-duration, but not lamivudine- or adefovir-duration. In post-hoc analysis using reconstructed TDF-duration (median 29.6months, IQR=15.0-36.1, n=31), average half-life of cccDNA was estimated at 9.2months (HBeAg-positive=8.6, HBeAg-negative=26.2) and total IH DNA at 5.8months (HBeAg-positive=1.3, HBeAg-negative=13.6). Intrahepatic viral loads remained detectable for all patients, even with prolonged TDF-exposure. In co-infection, TDF-use is associated with lower levels of HBV replication intermediates and cccDNA. Slow decay of intrahepatic viral loads underscores that TDF is unable to completely block intracellular viral DNA synthesis, which possibly accounts for continuous replenishment of the cccDNA pool. Chronic hepatitis B virus (HBV) is a persistent infection, while the only real way of

  6. Dolutegravir monotherapy in HIV-infected patients with sustained viral suppression.

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    Rojas, Jhon; Blanco, José L; Marcos, María A; Lonca, Montserrat; Tricas, Amparo; Moreno, Laura; Gonzalez-Cordon, Ana; Torres, Berta; Mallolas, Josep; Garcia, Federico; Gatell, Jose M; Martinez, Esteban

    2016-07-01

    We reviewed the 24 week outcomes of HIV-infected patients from our hospital who had their ART switched to dolutegravir monotherapy on an individual clinical basis. Retrospective hospital database assessment of virally suppressed patients in whom the treating physician had switched to 50 mg of dolutegravir once daily due to one or more of the following reasons: antiretroviral-related adverse effects; comorbidities; risk of interactions; or archived resistance. Patients had ≥24 weeks of follow-up. Population, virological and immunological responses and safety and tolerability are described. Thirty-three (22 on PIs, of whom 18 had ritonavir-boosted PI monotherapy) patients were identified: median (IQR) age of 56 (50-62) years, 55% women, median (IQR) of 19 (17-23) years of known HIV infection, 39% prior AIDS events, median (IQR) of 8 (4-13) years with undetectable plasma HIV-1 RNA and median (IQR) CD4 cell count of 596 (420-843) cells/mm(3). Twenty-five (76%) patients had antiretroviral-related adverse effects, 32 (97%) patients had comorbidities, 28 (85%) patients had risk of interactions and 16 (48%) patients had archived resistance. One patient with suboptimal adherence had low-level virological failure through weeks 4-24. HIV RNA genotypic resistance tests detected no integrase mutations at weeks 4 and 24, but 118R was detected in 7% of the integrated HIV DNA at 24 weeks. Patients had significant median decreases in triglycerides (-117 mg/dL), total cholesterol (-36 mg/dL), the total cholesterol/HDL cholesterol ratio (-0.7) and high-sensitivity C-reactive protein (-0.05 mg/dL) (P ≤ 0.007), although the Chronic Kidney Disease Epidemiology Collaboration equation also decreased (-7.1 mL/min) (P < 0.0001). These data suggest the efficacy of dolutegravir monotherapy as a maintenance strategy to be further confirmed in randomized clinical trials. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial

  7. Associations between health and productivity in cow-calf beef herds and persistent infection with bovine viral diarrhea virus, antibodies against bovine viral diarrhea virus, or antibodies against infectious bovine rhinotracheitis virus in calves.

    Science.gov (United States)

    Waldner, Cheryl L; Kennedy, Richard I

    2008-07-01

    To measure associations between health and productivity in cow-calf beef herds and persistent infection with bovine viral diarrhea virus (BVDV), antibodies against BVDV, or antibodies against infectious bovine rhinotracheitis (IBR) virus in calves. 1,782 calves from 61 beef herds. Calf serum samples were analyzed at weaning for antibodies against type 1 and type 2 BVDV and IBR virus. Skin biopsy specimens from 5,704 weaned calves were tested immunohistochemically to identify persistently infected (PI) calves. Herd production records and individual calf treatment and weaning weight records were collected. There was no association between the proportion of calves with antibodies against BVDV or IBR virus and herd prevalence of abortion, stillbirth, calf death, or nonpregnancy. Calf death risk was higher in herds in which a PI calf was detected, and PI calves were more likely to be treated and typically weighed substantially less than herdmates at weaning. Calves with high antibody titers suggesting exposure to BVDV typically weighed less than calves that had no evidence of exposure. BVDV infection, as indicated by the presence of PI calves and serologic evidence of infection in weaned calves, appeared to have the most substantial effect on productivity because of higher calf death risk and treatment risk and lower calf weaning weight.

  8. Host transcription factor Speckled 110 kDa (Sp110), a nuclear body protein, is hijacked by hepatitis B virus protein X for viral persistence.

    Science.gov (United States)

    Sengupta, Isha; Das, Dipanwita; Singh, Shivaram Prasad; Chakravarty, Runu; Das, Chandrima

    2017-12-15

    Promyelocytic leukemia nuclear bodies (PML-NB) are sub-nuclear organelles that are the hub of numerous proteins. DNA/RNA viruses often hijack the cellular factors resident in PML-NBs to promote their proliferation in host cells. Hepatitis B virus (HBV), belonging to Hepadnaviridae family, remains undetected in early infection as it does not induce the innate immune response and is known to be the cause of several hepatic diseases leading to cirrhosis and hepatocellular carcinoma. The association of PML-NB proteins and HBV is being addressed in a number of recent studies. Here, we report that the PML-NB protein Speckled 110 kDa (Sp110) is SUMO1-modified and undergoes a deSUMOylation-driven release from the PML-NB in the presence of HBV. Intriguingly, Sp110 knockdown significantly reduced viral DNA load in the culture supernatant by activation of the type I interferon-response pathway. Furthermore, we found that Sp110 differentially regulates several direct target genes of hepatitis B virus protein X (HBx), a viral co-factor. Subsequently, we identified Sp110 as a novel interactor of HBx and found this association to be essential for the exit of Sp110 from the PML-NB during HBV infection and HBx recruitment on the promoter of these genes. HBx, in turn, modulates the recruitment of its associated transcription cofactors p300/HDAC1 to these co-regulated genes, thereby altering the host gene expression program in favor of viral persistence. Thus, we report a mechanism by which HBV can evade host immune response by hijacking the PML-NB protein Sp110, and therefore, we propose it to be a novel target for antiviral therapy. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Single-Dose Universal Hepatitis A Immunization in Argentina: Low Viral Circulation and High Persistence of Protective Antibodies Up to 4 Years.

    Science.gov (United States)

    Vizzotti, C; González, J; Rearte, A; Urueña, A; Pérez Carrega, M; Calli, R; Gentile, A; Uboldi, A; Ramonet, M; Cañero-Velasco, M; Diosque, M

    2015-12-01

    Single-dose hepatitis A virus (HAV) vaccination was implemented in all Argentinean children aged 12 months in 2005. Between 2005 and 2011, a dramatic decline was observed in HAV infection rates, fulminant hepatitis, and liver transplantation. This study assessed current viral circulation and estimated protective antibody persistence 4 years after vaccination. Prevalence of prevaccination anti-HAV antibodies in 12-month-old children was evaluated as an indirect estimation of viral circulation (Group A). Seroprevalence was also measured in 5-year-old children who received 1 dose of HAV vaccine at 1 year of age (Group B). Blood samples were tested for immunoglobulin (Ig)G anti-HAV antibodies (seroprotection = ≥10 mIU/mL). All Group A-positive samples were tested for IgM anti-HAV antibodies to identify recent infections. Logistic regression analysis was done to evaluate associations between demographic and socioeconomic variables and seroprotection. Of 433 children from Group A, 29.5% (95% confidence interval [CI], 25.2-33.8) were positive for IgG anti-HAV antibodies with a geometric mean concentration (GMC) of 6.17 mIU/mL (95% CI, 5.33-7.15 mIU/mL); all IgM anti-HAV were negative. From 1139 in Group B, 93% (95% CI, 91.7-94.6) maintained seroprotection with a GMC of 97.96 mIU/mL (95% CI, 89.21-107.57 mIU/mL). Kindergarten attendance was associated with seroprotection in Group B (odds ratio [OR], 2.0; 95% CI, 1.26-3.3). In contrast, high maternal educational level was associated with a lack of seroprotection in this group (OR, .26; 95% CI, .09-.8). Single-dose, universal hepatitis A immunization in infants resulted in low HAV circulation and persistent immunologic protection up to 4 years in Argentina. Variables associated with presence or absence of seroprotection in vaccinated children could be related to differences in hygiene habits in settings with residual viral circulation. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric

  10. Mindful Persistence: Literacies for Taking up and Sustaining Fermented-Food Projects

    Science.gov (United States)

    Santana, Christina; Kuznetsov, Stacey; Schmeckpeper, Sheri; Curry, Linda J.; Long, Elenore; Davis, Lauren; Koerner, Heidi; McQuarrie, Kimberly Butterfield

    2015-01-01

    Almost by definition, resisting the insidious convenience of the mainstream food supply requires persistence. This is especially true for food projects requiring fermentation--projects that unfold over days or weeks and require day-to-day science in kitchens where variables can be hard to control and where some degree of periodic failure is almost…

  11. An occult hepatitis B-derived hepatoma cell line carrying persistent nuclear viral DNA and permissive for exogenous hepatitis B virus infection.

    Directory of Open Access Journals (Sweden)

    Chih-Lang Lin

    Full Text Available Occult hepatitis B virus (HBV infection is defined as persistence of HBV DNA in liver tissues, with or without detectability of HBV DNA in the serum, in individuals with negative serum HBV surface antigen (HBsAg. Despite accumulating evidence suggesting its important clinical roles, the molecular and virological basis of occult hepatitis B remains unclear. In an attempt to establish new hepatoma cell lines, we achieved a new cell line derived from a hepatoma patient with chronic hepatitis C virus (HCV and occult HBV infection. Characterization of this cell line revealed previously unrecognized properties. Two novel human hepatoma cell lines were established. Hep-Y1 was derived from a male hepatoma patient negative for HCV and HBV infection. Hep-Y2 was derived from a female hepatoma patient suffering from chronic HCV and occult HBV infection. Morphological, cytogenetic and functional studies were performed. Permissiveness to HBV infection was assessed. Both cell lines showed typical hepatocyte-like morphology under phase-contrast and electron microscopy and expressed alpha-fetoprotein, albumin, transferrin, and aldolase B. Cytogenetic analysis revealed extensive chromosomal anomalies. An extrachromosomal form of HBV DNA persisted in the nuclear fraction of Hep-Y2 cells, while no HBsAg was detected in the medium. After treated with 2% dimethyl sulfoxide, both cell lines were permissive for exogenous HBV infection with transient elevation of the replication intermediates in the cytosol with detectable viral antigens by immunoflurescence analysis. In conclusions, we established two new hepatoma cell lines including one from occult HBV infection (Hep-Y2. Both cell lines were permissive for HBV infection. Additionally, Hep-Y2 cells carried persistent extrachromosomal HBV DNA in the nuclei. This cell line could serve as a useful tool to establish the molecular and virological basis of occult HBV infection.

  12. How long can austerity persist? The factors that sustain fiscal consolidations

    Directory of Open Access Journals (Sweden)

    David Lodge

    2013-06-01

    Full Text Available To put public debt on a sustainable path, many governments face the task of enacting large fiscal consolidation followed by years of sustained primary surpluses. By estimating hazard functions for the duration of consolidations, we analyse the features of past consolidation efforts across a panel of advanced economies. Our contribution is to identify the factors that help to start and sustain consolidations, separately discussing governments’ “commitment” to the cause as well as their “capacity” for action. Our analysis suggests that longer consolidations are initiated when public debt is high, fiscal deficits are large, the interest burden heavy and long-term sovereign bond yields elevated. However, we also find that a countries’ “capacity” to change course is important. Higher initial private sector savings, a stronger external balance, a competitive position and stable financial conditions appear to provide more scope for governments to sustain longer-lasting consolidations. Once we have controlled for the initial macroeconomic conditions, there is a lesser role for governments’ commitment as reflected in factors such as the composition and the pace of the fiscal adjustment or the political cycle in explaining the duration of consolidation. However, commitment to permanent, rather than temporary, fiscal adjustment is key.

  13. Weaning management of newly received beef calves with or without continuous exposure to a persistently infected bovine viral diarrhea virus pen mate: Effects on rectal temperature, peripheral blood leukocytes and serum

    Science.gov (United States)

    Exposure to animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) results in immunomodulation in cohorts. It is hypothesized that the extent of modulation differs for preconditioned (PC) vs. auction market (AM) cattle. Our objective was to compare immune responses of PC or AM ca...

  14. Weaning management of newly received beef calves with or without exposure to a persistently infected bovine viral diarrhea virus type 1b calf: Effects on health, performance, BVDV type 1a titers, and circulating leukocytes

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) is a major culprit in the development of bovine respiratory disease (BRD) either directly via acute clinical illness or indirect effects of immunosuppression. Calves born persistently infected (PI) with BVDV are the primary transmission source of the virus; however...

  15. Pre-Arrival Management of Newly Received Beef Calves With or Without Exposure to a Persistently Infected Bovine Viral Diarrhea Virus Type I Calf Affects Health, Performance, BVDV Type I Titers, and Circulating Leukocytes

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) is a major culprit in the development of BRD either directly via acute clinical disease or through indirect effects of immunosuppression. Calves born persistently infected (PI) with BVDV are the primary vector for introduction of the virus into herds or productio...

  16. Persisting in papyrus: size, oxidative stress, and fitness in freshwater organisms adapted to sustained hypoxia.

    Science.gov (United States)

    Joyner-Matos, Joanna; Chapman, Lauren J

    2013-08-01

    Aquatic hypoxia is generally viewed as stressful for aerobic organisms. However, hypoxia may also benefit organisms by decreasing cellular stress, particularly that related to free radicals. Thus, an ideal habitat may have the minimum O2 necessary to both sustain aerobic metabolism and reduce the need to scavenge free radicals and repair free radical damage. The ability of aquatic organisms to sustain aerobic metabolism relates in part to the ability to maximize gas diffusion, which can be facilitated by small body size when O2 uptake occurs across the body surface, by a large gill surface area, or by the ability to use atmospheric air. We use water-breathing organisms in chronically hypoxic papyrus (Cyperus papyrus) swamps of East Africa to test the hypothesis that cellular-level benefits of hypoxia may translate into increased fitness, especially for small organisms. A review of recent studies of fingernail clams (Sphaerium sp.) shows that clams living in sustained hypoxia have minimized oxidative stress and that these cellular-level benefits may lead to increased fitness. We suggest that organisms in the extreme conditions in the papyrus swamps provide a unique opportunity to challenge the conventional classification of hypoxic habitats as 'stressful' and normoxic habitats as 'optimal.' Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Genetic characterization of bovine viral diarrhea virus strains in Beijing, China and innate immune responses of peripheral blood mononuclear cells in persistently infected dairy cattle.

    Science.gov (United States)

    Weng, Xiao Gang; Song, Quan Jiang; Wu, Qiong; Liu, Ming Chao; Wang, Meng Ling; Wang, Jiu Feng

    2015-01-01

    To acquire epidemiological data on the bovine viral diarrhea virus (BVDV) and identify cattle persistently infected (PI) with this virus, 4,327 samples from Holstein dairy cows were screened over a four-year period in Beijing, China. Eighteen BVD viruses were isolated, 12 from PI cattle. Based on genetic analysis of their 5'-untranslated region (5'-UTR), the 18 isolates were assigned to subgenotype BVDV-1m, 1a, 1d, 1q, and 1b. To investigate the innate immune responses in the peripheral-blood mononuclear cells of PI cattle, the expression of Toll-like receptors (TLRs), RIG-I-like receptors, interferon-α (IFN-α), IFN-β, myxovirus (influenza virus) resistance 1 (MX1), and interferon stimulatory gene 15 (ISG15) was assessed by qPCR. When compared with healthy cattle, the expression of TLR-7, IFN-α, and IFN-β mRNA was downregulated, but the expression of MX1 and ISG-15 mRNA was upregulated in PI cattle. Immunoblotting analysis revealed that the expression of interferon regulatory factor 3 (IRF-3) and IRF-7 was lower in PI cattle than in healthy cattle. Thus, BVDV-1m and 1a are the predominant subgenotypes in the Beijing region, and the strains are highly divergent. Our findings also suggest that the TLR-7/IRF-7 signaling pathway plays a role in evasion of host restriction by BVDV.

  18. Impact of clonal competition for peptide-MHC complexes on the CD8[superscript +] T-cell repertoire selection in a persistent viral infection

    Energy Technology Data Exchange (ETDEWEB)

    Wynn, Katherine K.; Fulton, Zara; Cooper, Leanne; Silins, Sharon L.; Gras, Stephanie; Archbold, Julia K.; Tynan, Fleur E.; Miles, John J.; McCluskey, James; Burrows, Scott R.; Rossjohn, Jamie; Khanna, Rajiv (Monash); (Queensland Inst. of Med. Rsrch.); (Melbourne)

    2008-04-29

    CD8{sup +} T-cell responses to persistent viral infections are characterized by the accumulation of an oligoclonal T-cell repertoire and a reduction in the naive T-cell pool. However, the precise mechanism for this phenomenon remains elusive. Here we show that human cytomegalovirus (HCMV)-specific CD8{sup +} T cells recognizing distinct epitopes from the pp65 protein and restricted through an identical HLA class I allele (HLA B*3508) exhibited either a highly conserved public T-cell repertoire or a private, diverse T-cell response, which was uniquely altered in each donor following in vitro antigen exposure. Selection of a public T-cell receptor (TCR) was coincident with an atypical major histocompatibility complex (MHC)-peptide structure, in that the epitope adopted a helical conformation that bulged from the peptide-binding groove, while a diverse TCR profile was observed in response to the epitope that formed a flatter, more 'featureless' landscape. Clonotypes with biased TCR usage demonstrated more efficient recognition of virus-infected cells, a greater CD8 dependency, and were more terminally differentiated in their phenotype when compared with the T cells expressing diverse TCR. These findings provide new insights into our understanding on how the biology of antigen presentation in addition to the structural features of the pMHC-I might shape the T-cell repertoire and its phenotype.

  19. Excreção e transmissão do vírus da diarréia viral bovina por bezerros persistentemente infectados Shedding and transmission of bovine viral diarrhea virus by persistently infected calves

    Directory of Open Access Journals (Sweden)

    Sandra Arenhart

    2009-09-01

    /48 (16,6% foram soropositivos para anticorpos no dia 10, 26/48 (54,1% no dia 40 e 37/48 (77% haviam soroconvertido no dia 100, quando encerrou-se o monitoramento. Estes resultados demonstram que a viremia e excreção viral contínua em altos títulos por animais PI assegura a transmissão rápida do BVDV a animais mantidos em contato, sendo a transmissão notadamente mais rápida em condições intensivas e de alta densidade animal.Persistently infected (PI calves born to cows infected with non-cytopathic bovine virus diarrhea virus (BVDV represent the main reservoir of the virus in nature. We herein report an investigation on the patterns of virus shedding and transmission by five PI calves produced experimentally through inoculation of pregnant cows with Brazilian BVDV isolates. Five calves that survived intrauterine infection were born healthy, lacking neutralizing antibodies to BVDV and harboring virus in the blood. After weaning - and following the disappearance of colostral antibodies - PI calves were monitored for virus in serum and body secretions (ocular, oral, nasal and genital at weekly intervals for up to 150 days. For each animal, the virus titers in serum showed minor variations throughout the collections (with one exception that presented an increase late in infection, yet the titers varied widely among animals (from 10² to 10(6TCID50/mL. Virus shedding in secretions was detected steadily during all the observation period with minor titer variations for each particular animal. The highest titers were generally detected in nasal and ocular secretions (titers 10(4 to 10(6TCID50mL whereas genital and oral secretions usually contained low amount of virus (10² to 10³TCID50mL. To evaluate the kinetics of virus transmission by these animals, one PI was introduced on a group of 10 seronegative calves maintained with a high animal density simulating the conditions of an intensive management. All 10 contact calves seroconverted to BVDV by day 30. Another PI calf

  20. Host factors influencing viral persistence

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Nansen, A; Ørding Andreasen, Susanne

    2000-01-01

    With the aim of characterizing the antiviral immune response to a non-cytocidal virus, we studied the outcome of lymphocytic choriomeningitis virus infection in a number of gene knockout mouse strains. Two virus strains differing markedly in their capacity to spread and replicate inside the murine....... Reappearance of virus is associated with impaired long-term CD8+ T-cell mediated immune surveillance, and the time to virus resurgence is inversely correlated to the replication rate of the virus. Our studies also reveal that interferon-gamma is a central cytokine, and depending on the rate of virus...

  1. Genetics and Genomics of Cotton Leaf Curl Disease, Its Viral Causal Agents and Whitefly Vector: A Way Forward to Sustain Cotton Fiber Security

    Directory of Open Access Journals (Sweden)

    Mehboob-ur- Rahman

    2017-07-01

    Full Text Available Cotton leaf curl disease (CLCuD after its first epidemic in 1912 in Nigeria, has spread to different cotton growing countries including United States, Pakistan, India, and China. The disease is of viral origin—transmitted by the whitefly Bemisia tabaci, which is difficult to control because of the prevalence of multiple virulent viral strains or related species. The problem is further complicated as the CLCuD causing virus complex has a higher recombination rate. The availability of alternate host crops like tomato, okra, etc., and practicing mixed type farming system have further exaggerated the situation by adding synergy to the evolution of new viral strains and vectors. Efforts to control this disease using host plant resistance remained successful using two gene based-resistance that was broken by the evolution of new resistance breaking strain called Burewala virus. Development of transgenic cotton using both pathogen and non-pathogenic derived approaches are in progress. In future, screening for new forms of host resistance, use of DNA markers for the rapid incorporation of resistance into adapted cultivars overlaid with transgenics and using genome editing by CRISPR/Cas system would be instrumental in adding multiple layers of defense to control the disease—thus cotton fiber production will be sustained.

  2. Deep sequencing of the viral phoH gene reveals temporal variation, depth-specific composition, and persistent dominance of the same viral phoH genes in the Sargasso Sea

    Directory of Open Access Journals (Sweden)

    Dawn B. Goldsmith

    2015-06-01

    Full Text Available Deep sequencing of the viral phoH gene, a host-derived auxiliary metabolic gene, was used to track viral diversity throughout the water column at the Bermuda Atlantic Time-series Study (BATS site in the summer (September and winter (March of three years. Viral phoH sequences reveal differences in the viral communities throughout a depth profile and between seasons in the same year. Variation was also detected between the same seasons in subsequent years, though these differences were not as great as the summer/winter distinctions. Over 3,600 phoH operational taxonomic units (OTUs; 97% sequence identity were identified. Despite high richness, most phoH sequences belong to a few large, common OTUs whereas the majority of the OTUs are small and rare. While many OTUs make sporadic appearances at just a few times or depths, a small number of OTUs dominate the community throughout the seasons, depths, and years.

  3. 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.

  4. Hodgkin lymphoma is as common as non-Hodgkin lymphoma in HIV-positive patients with sustained viral suppression and limited immune deficiency: a prospective cohort study.

    Science.gov (United States)

    Hoffmann, C; Hentrich, M; Gillor, D; Behrens, G; Jensen, B; Stoehr, A; Esser, S; van Lunzen, J; Krznaric, I; Müller, M; Oette, M; Hensel, M; Thoden, J; Fätkenheuer, G; Wyen, C

    2015-04-01

    The incidence of HIV-related non-Hodgkin lymphoma (NHL) but not that of Hodgkin lymphoma (HL) has been declining. The aim of the study was to compare HIV-infected patients with NHL and HL with respect to antiretroviral therapy (ART) exposure at the time of lymphoma diagnosis. HIV-infected patients with NHL and HL included in a prospective multicentre cohort study since January 2005 were compared with respect to ART exposure and viral load at the time of lymphoma diagnosis. As of 31 December 2012, data for 329 patients with NHL and 86 patients with HL from 31 participating centres were available. Patients with HL were more likely to be on ART (73.5% vs. 39.1%, respectively; P  12 months and a CD4 cell count of > 200 cells/μL. Of note, 45.8% of all patients with NHL were not currently on ART and had a CD4 count of < 350 cells/μL. This prospective cohort study shows that HL was as common as NHL in patients with sustained viral suppression and limited immune deficiency. In contrast to NHL, the majority of patients with HL were on effective ART, suggesting that ART provides insufficient protection from developing HL. The high proportion of untreated patients with NHL suggests missed opportunities for earlier initiation of ART. © 2014 British HIV Association.

  5. IL28B SNP rs12979860 is the Critical Predictor for Sustained Viral Response in Chinese Children Aged 1 to 6 Years with Chronic Hepatitis C.

    Science.gov (United States)

    Zhong, Yan-Wei; Zhang, Hong-Fei; Shi, Yan-Min; Li, Yong-Li; Chu, Fang; Xu, Zhi-Qiang; Chen, Da-Wei; Gan, Yu; Wang, Fu-Chuan; Gu, Mei-Lei; Dong, Yi; Zhu, Shi-Shu; Shi, Ce; Fan, Hua-Hao; Zhang, Xiu-Chang; Zhang, Min

    2016-01-01

    Clinical data on children with chronic hepatitis C (CHC) remain extremely limited. This study investigated sustained virologic response (SVR) to alfa-interferon 2b plus RBV treatment in children aged 1-6 years with unsafe injection-acquired CHC. 154 children with CHC aged 1 to 6 years were enrolled, 101 of them were male (65.6%) and 53 were female (34.4%), and they were treated with alfa-interferon at a dose of 1-5 MIU/m(2) 3 times weekly plus oral RBV (15 mg/kg/day) for 48 weeks. 57(39.3 %) of them were genotype 1b, 73(50.3%) were genotypes 2a, 15(10.3%) were undecided type. SVR was achieved in 53 of 57(93.0%) patients with genotype 1b, in 72 (98.6%) of 73 with genotype 2a, 15(100.0%) of 15 with undecided type. There was no significant statistical difference in SVR between male and female (98.0% vs 94.3%, p=0.340), genotype 2a and those with genotype 1b(98.6% vs 93.0%, p=0.160), ALT>40U/L group and ALT≤40U/L group(96.7% vs 96.8%, p=1.000), AST>40U/L group and AST≤40U/L group(95.9% vs 98.2%, p=0.654) as well as lower baseline viral load group (<6×10(5) IU/ml) and higher baseline viral load group(≥6×10(5) IU/ml)(97.3% vs 95.3%, p=0.916). Leucopenia, neutropenia, hemoglobin concentration decrease, fever, platelet count decrease and rash were 8.4%, 69.5%, 24.0%, 50.6%, 1.9% and 4.5%, respectively. And only 12(7.8%) individuals developed thyroid autoantibodies. The SVR was higher in patients with IL-28B genotype C/C than C/T (99.0% vs 80%, p=0.002). Compared with HCV viral genotype, ALT level and baseline viral load, IL-28B rs12979860 is more suitable for predicting antiviral efficacy in children with CHC. It is inappropriate to take the increase of ALT level as an essential indicator for antiviral treatment in children aged 1-6 years.

  6. 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...

  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. Enhanced susceptibility to subcutaneous abscess formation and persistent infection around catheters is associated with sustained interleukin-1beta levels

    NARCIS (Netherlands)

    Boelens, J. J.; Zaat, S. A.; Murk, J. L.; Weening, J. J.; van der Poll, T.; Dankert, J.

    2000-01-01

    A persistent Staphylococcus epidermidis infection in mice around a subcutaneous polyvinylpyrrolidone-grafted silicon elastomer catheter (SEpvp) but not around a conventional silicon elastomer catheter was observed. With SEpvp pericatheter tissue, protracted and exaggerated interleukin-1beta

  9. T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections.

    Science.gov (United States)

    Utzschneider, Daniel T; Charmoy, Mélanie; Chennupati, Vijaykumar; Pousse, Laurène; Ferreira, Daniela Pais; Calderon-Copete, Sandra; Danilo, Maxime; Alfei, Francesca; Hofmann, Maike; Wieland, Dominik; Pradervand, Sylvain; Thimme, Robert; Zehn, Dietmar; Held, Werner

    2016-08-16

    Chronic infections promote the terminal differentiation (or "exhaustion") of T cells and are thought to preclude the formation of memory T cells. In contrast, we discovered a small subpopulation of virus-specific CD8(+) T cells that sustained the T cell response during chronic infections. These cells were defined by, and depended on, the expression of the transcription factor Tcf1. Transcriptome analysis revealed that this population shared key characteristics of central memory cells but lacked an effector signature. Unlike conventional memory cells, Tcf1-expressing T cells displayed hallmarks of an "exhausted" phenotype, including the expression of inhibitory receptors such as PD-1 and Lag-3. This population was crucial for the T cell expansion that occurred in response to inhibitory receptor blockade during chronic infection. These findings identify a memory-like T cell population that sustains T cell responses and is a prime target for therapeutic interventions to improve the immune response in chronic infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Novel use of surveillance data to detect HIV-infected persons with sustained high viral load and durable virologic suppression in New York City.

    Directory of Open Access Journals (Sweden)

    Arpi S Terzian

    Full Text Available BACKGROUND: Monitoring of the uptake and efficacy of ART in a population often relies on cross-sectional data, providing limited information that could be used to design specific targeted intervention programs. Using repeated measures of viral load (VL surveillance data, we aimed to estimate and characterize the proportion of persons living with HIV/AIDS (PLWHA in New York City (NYC with sustained high VL (SHVL and durably suppressed VL (DSVL. METHODS/PRINCIPAL FINDINGS: Retrospective cohort study of all persons reported to the NYC HIV Surveillance Registry who were alive and ≥12 years old by the end of 2005 and who had ≥2 VL tests in 2006 and 2007. SHVL and DSVL were defined as PLWHA with 2 consecutive VLs ≥100,000 copies/mL and PLWHA with all VLs ≤400 copies/mL, respectively. Logistic regression models using generalized estimating equations were used to model the association between SHVL and covariates. There were 56,836 PLWHA, of whom 7% had SHVL and 38% had DSVL. Compared to those without SHVL, persons with SHVL were more likely to be younger, black and have injection drug use (IDU risk. PLWHA with SHVL were more likely to die by 2007 and be younger by nearly ten years, on average. CONCLUSIONS/SIGNIFICANCE: Nearly 60% of PLWHA in 2005 had multiple VLs, of whom almost 40% had DSVL, suggesting successful ART uptake. A small proportion had SHVL, representing groups known to have suboptimal engagement in care. This group should be targeted for additional outreach to reduce morbidity and secondary transmission. Measures based on longitudinal analyses of surveillance data in conjunction with cross-sectional measures such as community viral load represent more precise and powerful tools for monitoring ART effectiveness and potential impact on disease transmission than cross-sectional measures alone.

  11. Evaluation of the effects of long-term storage of bovine ear notch samples on the ability of 2 diagnostic assays to identify calves persistently infected with bovine viral diarrhoea virus

    Directory of Open Access Journals (Sweden)

    F. Khan

    2011-04-01

    Full Text Available Research aimed at optimising diagnostic laboratory procedures is central to the development of effective bovine viral diarrhoea virus (BVDV control programmes. BVDV is a singlestranded RNA virus that crosses the placenta to infect foetuses, resulting in reproductive losses due to foetal death or persistently infected calves that die early in life. Persistently infected animals are widely accepted to be the primary reservoir of BVDV and the largest source of infection. This poses important challenges to overall animal/herd health and can cause major losses to the cattle industry. Long-term storage of bovine ear notch samples from calves persistently infected with BVDV may adversely affect the ability of diagnostic assays to detect the virus efficiently. In order to test this hypothesis, ear notch samples from 7 animals were divided into 2 groups. One set was subjected to prompt formalin fixation and the other set stored either as fresh samples without preservatives at –2 °C, or soaked overnight in phosphate buffered saline followed by freezing of the supernatant fluid at –2 °C. Frozen ear notches and ear notch supernatant yielded positive results with an antigen- capture, enzyme linked immunosorbent assay (AC-ELISA for the duration of the study (6 months and optical density (OD values remained significantly within range. There was no significant difference between storing fresh ear notch samples or PBS at –2 °C. However, positive immunohistochemistry (IHC staining on formalin fixed ear notches started to fade between Day 17 and Day 29 when stored at room temperature. It was concluded that fresh ear notches could safely be stored at –2 °C for a period of 6 months prior to testing for BVD viral antigens.

  12. Evaluation of the effects of long-term storage of bovine ear notch samples on the ability of 2 diagnostic assays to identify calves persistently infected with bovine viral diarrhoea virus.

    Science.gov (United States)

    Khan, F; Vorster, J H; van Vuuren, M; Mapham, P

    2011-03-01

    Research aimed at optimising diagnostic laboratory procedures is central to the development of effective bovine viral diarrhoea virus (BVDV) control programmes. BVDV is a single-stranded RNA virus that crosses the placenta to infect foetuses, resulting in reproductive losses due to foetal death or persistently infected calves that die early in life. Persistently infected animals are widely accepted to be the primary reservoir of BVDV and the largest source of infection. This poses important challenges to overall animal/herd health and can cause major losses to the cattle industry. Long-term storage of bovine ear notch samples from calves persistently infected with BVDV may adversely affect the ability of diagnostic assays to detect the virus efficiently. In order to test this hypothesis, ear notch samples from 7 animals were divided into 2 groups. One set was subjected to prompt formalin fixation and the other set stored either as fresh samples without preservatives at -2 degrees C, or soaked overnight in phosphate buffered saline followed by freezing of the supernatant fluid at -2 degrees C. Frozen ear notches and ear notch supernatant yielded positive results with an antigen-capture, enzyme linked immunosorbent assay (AC-ELISA) for the duration of the study (6 months) and optical density (OD) values remained significantly within range. There was no significant difference between storing fresh ear notch samples or PBS at -2 degrees C. However, positive immunohistochemistry (IHC) staining on formalin fixed ear notches started to fade between Day 17 and Day 29 when stored at room temperature. It was concluded that fresh ear notches could safely be stored at -2 degrees C for a period of 6 months prior to testing for BVD viral antigens.

  13. Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.

    Directory of Open Access Journals (Sweden)

    Antonio Rivero-Juarez

    Full Text Available AIM: To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients. METHODS: HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6. Rapid and sustained virological response (RVR and SVR rates were also analyzed. RESULTS: Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week 1: p = 0.01; week 2: p = 0.038; week 4: p = 0.03. Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031. With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week 1: p<0.001; week 2: p = 0.01; week 4: p = 0.02, RVR (p = 0.015 and SVR (p = 0.029 than those not carrying KIR3DS1. CONCLUSION: Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.

  14. Human Cytomegalovirus Persistence

    OpenAIRE

    Goodrum, Felicia; Caviness, Katie; Zagallo, Patricia

    2012-01-01

    Viral persistence is the rule following infection with all herpesviruses. The β-herpesvirus, human cytomegalovirus (HCMV), persists through chronic and latent states of infection. Both the chronic and latent states of infection contribute to HCMV persistence and to the high HCMV seroprevalence worldwide. The chronic infection is poorly defined molecularly, but clinically manifests as low-level virus shedding over extended periods of time and often in the absence of symptoms. Latency requires ...

  15. Progressive loss of CD3 expression after HTLV-I infection results from chromatin remodeling affecting all the CD3 genes and persists despite early viral genes silencing

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    Martiat Philippe

    2007-09-01

    Full Text Available Abstract Background HTLV-I infected CD4+ T-cells lines usually progress towards a CD3- or CD3low phenotype. In this paper, we studied expression, kinetics, chromatin remodeling of the CD3 gene at different time-points post HTLV-I infection. Results The onset of this phenomenon coincided with a decrease of CD3γ followed by the subsequent progressive reduction in CD3δ, then CD3ε and CD3ζ mRNA. Transient transfection experiments showed that the CD3γ promoter was still active in CD3- HTLV-I infected cells demonstrating that adequate amounts of the required transcription factors were available. We next looked at whether epigenetic mechanisms could be responsible for this progressive decrease in CD3 expression using DNase I hypersensitivity (DHS experiments examining the CD3γ and CD3δ promoters and the CD3δ enhancer. In uninfected and cells immediately post-infection all three DHS sites were open, then the CD3γ promoter became non accessible, and this was followed by a sequential closure of all the DHS sites corresponding to all three transcriptional control regions. Furthermore, a continuous decrease of in vivo bound transcription initiation factors to the CD3γ promoter was observed after silencing of the viral genome. Coincidently, cells with a lower expression of CD3 grew more rapidly. Conclusion We conclude that HTLV-I infection initiates a process leading to a complete loss of CD3 membrane expression by an epigenetic mechanism which continues along time, despite an early silencing of the viral genome. Whether CD3 progressive loss is an epiphenomenon or a causal event in the process of eventual malignant transformation remains to be investigated.

  16. Persistent genital tract HIV-1 RNA shedding after change in treatment regimens in antiretroviral-experienced women with detectable plasma viral load.

    Science.gov (United States)

    Venkatesh, Kartik K; DeLong, Allison K; Kantor, Rami; Chapman, Stacey; Ingersoll, Jessica; Kurpewski, Jaclynn; De Pasquale, Maria Pia; D'Aquila, Richard; Caliendo, Angela M; Cu-Uvin, Susan

    2013-04-01

    To longitudinally assess the association between plasma viral load (PVL) and genital tract human immunodeficiency virus (GT HIV) RNA among HIV-1 infected women changing highly active antiretroviral therapy (HAART) because of detectable PVL on current treatment. Women were eligible for the study if they had detectable PVL (defined as two consecutive samples with PVL>1000 copies/mL) and intended to change their current HAART regimen at the time of enrollment. Paired plasma and GT HIV-1 RNA were measured prospectively over 3 years. Longitudinal analyses examined rates of GT HIV-1 RNA shedding and the association with PVL. Sixteen women were followed for a median of 11 visits contributing a total of 205 study visits. At study enrollment, all had detectable PVL and 69% had detectable GT HIV-1 RNA. Half of the women changed to a new HAART regimen with ≥3 active antiretroviral drugs. The probability of having detectable PVL ≥30 days after changing HAART was 0.56 (95% CI: 0.37 to 0.74). Fourteen women (88%) had detectable PVL on a follow-up visit ≥30 or 60 days after changing HAART; and 12 women (75%) had detectable GT HIV-1 RNA on a follow-up visit ≥30 or 60 days after changing HAART. When PVL was undetectable, GT shedding occurred at 11% of visits, and when PVL was detectable, GT shedding occurred at 47% of visits. Some treatment-experienced HIV-infected women continue to have detectable virus in both the plasma and GT following a change in HAART, highlighting the difficulty of viral suppression in this patient population.

  17. Human cytomegalovirus persistence.

    Science.gov (United States)

    Goodrum, Felicia; Caviness, Katie; Zagallo, Patricia

    2012-05-01

    Viral persistence is the rule following infection with all herpesviruses. The β-herpesvirus, human cytomegalovirus (HCMV), persists through chronic and latent states of infection. Both of these states of infection contribute to HCMV persistence and to the high HCMV seroprevalence worldwide. The chronic infection is poorly defined molecularly, but clinically manifests as low-level virus shedding over extended periods of time and often in the absence of symptoms. Latency requires long-term maintenance of viral genomes in a reversibly quiescent state in the immunocompetent host. In this review, we focus on recent advances in the biology of HCMV persistence, particularly with respect to the latent mode of persistence. Latently infected individuals harbour HCMV genomes in haematopoietic cells and maintain large subsets of HCMV-specific T-cells. In the last few years, impressive advances have been made in understanding virus-host interactions important to HCMV infection, many of which will profoundly impact HCMV persistence. We discuss these advances and their known or potential impact on viral latency. As herpesviruses are met with similar challenges in achieving latency and often employ conserved strategies to persist, we discuss current and future directions of HCMV persistence in the context of the greater body of knowledge regarding α- and γ-herpesviruses persistence. © 2012 Blackwell Publishing Ltd.

  18. 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.

  19. E2F/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection.

    Directory of Open Access Journals (Sweden)

    Yueting Zheng

    2016-01-01

    Full Text Available Interferons (IFNs are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity. IFNs have broad antiviral properties and function by different mechanisms. IFNs fail to inhibit wild-type Adenovirus (Ad replication in established cancer cell lines. In this study, we analyzed the effects of IFNs on Ad replication in normal human cells. Our data demonstrate that both IFNα and IFNγ blocked wild-type Ad5 replication in primary human bronchial epithelial cells (NHBEC and TERT-immortalized normal human diploid fibroblasts (HDF-TERT. IFNs inhibited the replication of divergent adenoviruses. The inhibition of Ad5 replication by IFNα and IFNγ is the consequence of repression of transcription of the E1A immediate early gene product. Both IFNα and IFNγ impede the association of the transactivator GABP with the E1A enhancer region during the early phase of infection. The repression of E1A expression by IFNs requires a conserved E2F binding site in the E1A enhancer, and IFNs increased the enrichment of the E2F-associated pocket proteins, Rb and p107, at the E1A enhancer in vivo. PD0332991 (Pabociclib, a specific CDK4/6 inhibitor, dephosphoryles pocket proteins to promote their interaction with E2Fs and inhibited wild-type Ad5 replication dependent on the conserved E2F binding site. Consistent with this result, expression of the small E1A oncoprotein, which abrogates E2F/pocket protein interactions, rescued Ad replication in the presence of IFNα or IFNγ. Finally, we established a persistent Ad infection model in vitro and demonstrated that IFNγ suppresses productive Ad replication in a manner dependent on the E2F binding site in the E1A enhancer. This is the first study that probes the molecular basis of persistent adenovirus infection and reveals a novel mechanism by which adenoviruses utilize IFN signaling to suppress lytic virus replication and to promote persistent infection.

  20. 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.

  1. 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.

  2. Low levels of microbial translocation marker LBP are associated with sustained viral response after anti-HCV treatment in HIV-1/HCV co-infected patients.

    Directory of Open Access Journals (Sweden)

    Jessica Nyström

    Full Text Available Microbial translocation (MT contributes to immune activation during HIV and HCV infections. We investigated the kinetics of MT markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS, lipopolysaccharide binding protein (LBP and soluble CD14 (sCD14 could predict anti-HCV treatment outcome.Plasma from 78 HIV-infected patients was evaluated for LPS, LBP and sCD14. The patients starting anti-HCV treatment (with ongoing antiretroviral (ART treatment were categorized into sustained viral responders (SVR; n = 21 or non-responders (NR; n = 15 based on treatment outcome. ART starting subjects--were categorized into chronically HCV-infected (CH; n = 24 and mono-infected (HIV; n = 18, based on the HCV infection status. Samples were collected before start (at baseline of pegylated-interferon-alpha/ribavirin (peg-IFN/RBV or antiretroviral-therapy and two years after treatment start (at follow up. χ2-test, non-parametric statistics and logistic regression were applied to determine the associations with treatment response and changes of the soluble markers.Plasma levels of LPS and sCD14 were elevated in all subjects before antiviral-treatment but remained unchanged at follow-up. Elevated levels of LBP were present in patients with HIV and HIV/HCV co-infection and were reduced by ART. Additionally, higher levels of LBP were present at baseline in NR vs. SVR. Higher levels of LBP at baseline were associated with non-response to peg-IFN/RBV treatment in both bivariate (OR: 0.19 95% CI: 0.06-0.31, p = 0.004 and multivariate analysis (OR: 1.43, 95% CI: 1.1-1.86, p = 0.07.In HIV/HCV co-infected patients high baseline LBP levels are associated with non-response to peg-IFN/RBV therapy. Plasma LBP (decreased by ART may be a more relevant MT marker than LPS and sCD14.

  3. First-line cART regimen impacts the course of CD8+ T-cell counts in HIV-infected patients that achieve sustained undetectable viral load.

    Science.gov (United States)

    Poizot-Martin, Isabelle; Allavena, Clotilde; Delpierre, Cyrille; Duvivier, Claudine; Obry-Roguet, Véronique; Cano, Carla E; Guillouet de Salvador, Francine; Rey, David; Dellamonica, Pierre; Cheret, Antoine; Cuzin, Lise; Katlama, Christine; Cabié, André; Hoen, Bruno

    2016-10-01

    The aim of the study was to investigate the impact of first-line combined antiretroviral therapy (cART) regimen on the course of CD8 T-cell counts in human immunodeficiency virus (HIV)-infected patients.A retrospective observational study conducted on the French DAT'AIDS Cohort of HIV-infected patients.We selected 605 patients initiating a first-line cART between 2002 and 2009, and which achieved a sustained undetectable HIV plasma viral load (pVL) for at least 12 months without cART modification. The evolution of CD8 T-cell counts according to cART regimen was assessed.CD8 T-cell counts were assessed in 572 patients treated with 2NRTIs+1PI/r (n= 297), 2NRTIs+1NNRTI (n= 207) and 3NRTIs (n= 68). In multivariate analysis, after 12 months of follow-up, the 3NRTIs regimen was associated with a significantly smaller decrease of CD8 T-cell count compared with NNRTI-containing regimens (-10.2 cells/μL in 3NRTIs vs -105.1 cells/μL; P=0.02) but not compared with PI-containing regimens (10.2 vs -60.9 cells/μL; P=0.21). After 24 months, the 3NRTIs regimen was associated with a smaller decrease of CD8 T-cell count and % compared with PI/r- and NNRTI-containing regimens (0.2 in 3NRTIs vs -9.9 with PI/r-regimens, P=0.001, and vs -11.1 with NNRTI-regimens, p < 0.0001). A focus analysis on 11 patients treated with an INSTI-containing cART regimen during the study period showed after 12 months of follow-up, a median decrease of CD8 T-cell count of -155 [inter quartile range: -302; -22] cells/μL.Our data highlight the fact that cART regimens have differential effects on CD8 pool down regulation.

  4. 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...

  5. Sensitivity of reentrant driver localization to electrophysiological parameter variability in image-based computational models of persistent atrial fibrillation sustained by a fibrotic substrate

    Science.gov (United States)

    Deng, Dongdong; Murphy, Michael J.; Hakim, Joe B.; Franceschi, William H.; Zahid, Sohail; Pashakhanloo, Farhad; Trayanova, Natalia A.; Boyle, Patrick M.

    2017-09-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, causing morbidity and mortality in millions worldwide. The atria of patients with persistent AF (PsAF) are characterized by the presence of extensive and distributed atrial fibrosis, which facilitates the formation of persistent reentrant drivers (RDs, i.e., spiral waves), which promote fibrillatory activity. Targeted catheter ablation of RD-harboring tissues has shown promise as a clinical treatment for PsAF, but the outcomes remain sub-par. Personalized computational modeling has been proposed as a means of non-invasively predicting optimal ablation targets in individual PsAF patients, but it remains unclear how RD localization dynamics are influenced by inter-patient variability in the spatial distribution of atrial fibrosis, action potential duration (APD), and conduction velocity (CV). Here, we conduct simulations in computational models of fibrotic atria derived from the clinical imaging of PsAF patients to characterize the sensitivity of RD locations to these three factors. We show that RDs consistently anchor to boundaries between fibrotic and non-fibrotic tissues, as delineated by late gadolinium-enhanced magnetic resonance imaging, but those changes in APD/CV can enhance or attenuate the likelihood that an RD will anchor to a specific site. These findings show that the level of uncertainty present in patient-specific atrial models reconstructed without any invasive measurements (i.e., incorporating each individual's unique distribution of fibrotic tissue from medical imaging alongside an average representation of AF-remodeled electrophysiology) is sufficiently high that a personalized ablation strategy based on targeting simulation-predicted RD trajectories alone may not produce the desired result.

  6. Efficacy of four commercially available multivalent modified-live virus vaccines against clinical disease, viremia, and viral shedding in early-weaned beef calves exposed simultaneously to cattle persistently infected with bovine viral diarrhea virus and cattle acutely infected with bovine herpesvirus 1.

    Science.gov (United States)

    Chamorro, Manuel F; Walz, Paul H; Passler, Thomas; Palomares, Roberto; Newcomer, Benjamin W; Riddell, Kay P; Gard, Julie; Zhang, Yijing; Galik, Patricia

    2016-01-01

    To evaluate the efficacy of 4 commercially available multivalent modified-live virus vaccines against clinical disease, viremia, and viral shedding caused by bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BHV1) in early-weaned beef calves. 54 early-weaned beef steers (median age, 95 days). Calves were randomly assigned to 1 of 5 groups and administered PBSS (group A [control]; n = 11) or 1 of 4 commercially available modified-live virus vaccines that contained antigens against BHV1, BVDV types 1 (BVDV1) and 2 (BVDV2), parainfluenza type 3 virus, and bovine respiratory syncytial virus (groups B [11], C [10], D [11], and E [11]). Forty-five days after vaccination, calves were exposed simultaneously to 6 cattle persistently infected with BVDV and 8 calves acutely infected with BHV1 for 28 days (challenge exposure). For each calf, serum antibody titers against BVDV and BHV1 were determined before vaccination and before and after challenge exposure. Virus isolation was performed on nasal secretions, serum, and WBCs at predetermined times during the 28-day challenge exposure. None of the calves developed severe clinical disease or died. Mean serum anti-BHV1 antibody titers did not differ significantly among the treatment groups at any time and gradually declined during the study. Mean serum anti-BVDV antibody titers appeared to be negatively associated with the incidence of viremia and BVDV shedding. The unvaccinated group (A) had the lowest mean serum anti-BVDV antibody titers. The mean serum anti-BVDV antibody titers for group D were generally lower than those for groups B, C, and E. Results indicated differences in vaccine efficacy for the prevention of BVDV viremia and shedding in early-weaned beef calves.

  7. Are restored side channels sustainable aquatic habitat features? Predicting the potential persistence of side channels as aquatic habitats based on their fine sedimentation dynamics

    Science.gov (United States)

    Riquier, Jérémie; Piégay, Hervé; Lamouroux, Nicolas; Vaudor, Lise

    2017-10-01

    The restoration of side channels (also referred to as abandoned channels, former channels, floodplain channels, or side arms) is increasingly implemented to improve the ecological integrity of river-floodplain systems. However, the design of side channel restoration projects remains poorly informed by theory or empirical observations despite the increasing number of projects. Moreover, feedback regarding the hydromorphological adjustment of restored channels is rarely documented, making it difficult to predict channel persistence as aquatic habitats. In this study, we analyze the spatial and temporal patterns of fine sediment deposition (sedimentation rates ranged from 0 to 40.3 cm·y- 1 and reached 90.3 cm·y- 1 locally. Some channels exhibited a significant decline of sedimentation rates through time, whereas others maintained rather constant rates. Scouring processes (i.e., self-rejuvenation capacity) were occasionally documented in 15 channels. Six of the 16 studied channels appeared to be self-sustaining. The 10 others accumulated more and more fine sediment deposits after restoration. Parametric modeling of sedimentation rates suggested that among these 10 channels, four have long life-durations (i.e., more than a century), three have intermediate life-durations (i.e., likely between three and nine decades), and three others have short life-durations (i.e., likely between two and five decades). Observed channel-averaged sedimentation rates can be predicted from the frequency and magnitude (i.e., maximum shear stress) of upstream overflow events and the maximum intensity of backflow events (i.e., maximum backflow capacity). These predictors reflect the dominant role of side channel geometry (i.e., morphology of the upstream alluvial plug, slope conditions) in controlling their flooding regime. These models applied successfully to a wide range of channel morphologies and can be used to quantify a priori the likely effects and the sustainability of side channel

  8. Follicular bronchiolitis in an HIV-infected individual on combination antiretroviral therapy with low CD4+ cell count but sustained viral suppression

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Pedersen, Court; Madsen, Helle D

    2017-01-01

    A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis and was ......A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis...

  9. 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 ...

  10. Comparison of serum, ear notches, and nasal and saliva swabs for Bovine viral diarrhea virus antigen detection in colostrum-fed persistently infected (PI) calves and non-PI calves.

    Science.gov (United States)

    Lanyon, Sasha R; Sims, Sarah K; Cockcroft, Peter D; Reichel, Michael P

    2014-11-01

    The diagnosis of neonatal and young calves persistently infected (PI) with Bovine viral diarrhea virus (BVDV) by antigen-capture enzyme-linked immunosorbent assay (ACE) may be complicated by interference from colostrum-derived specific antibodies. Ten calves, with 3 calves identified as PI and 7 as non-PI were used in the current study. All non-PI calves were shown to be seropositive for BVDV-specific antibodies by antibody enzyme-linked immunosorbent assay (Ab-ELISA) on serum. Serum samples, ear notch samples, and nasal and saliva swabs were collected from each calf from birth until 12 weeks of age and tested by ELISA for BVDV-specific antigen and antibodies. Following colostrum ingestion, Ab-ELISA sample-to-positive (S/P) ratios rose by a mean of 0.95 (95% confidence interval [CI] = 0.64-1.25) and 1.72 (95% CI = 1.55-1.89) in seropositive, non-PI calves and in PI calves, respectively. The mean S/P ratios then declined to approximately 1.1 in non-PI calves and 0.5 in PI calves at between 60 and 80 days of age. In PI calves, testing for antigen in serum and nasal and saliva swabs was subject to interference by colostrum-derived antibodies in calves up to 3 weeks of age. Nasal swabs were less affected than serum and saliva swabs. Ear notches maintained positive ACE corrected optical densities at all sample times, despite a drop in the signal following the ingestion of colostrum. © 2014 The Author(s).

  11. Effects of Interferon-α/β on HBV Replication Determined by Viral Load

    Science.gov (United States)

    Tian, Yongjun; Chen, Wen-ling; Ou, Jing-hsiung James

    2011-01-01

    Interferons α and β (IFN-α/β) are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV) patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low. PMID:21829354

  12. Type-I Interferon Responses: From Friend to Foe in the Battle against Chronic Viral Infection.

    Science.gov (United States)

    Murira, Armstrong; Lamarre, Alain

    2016-01-01

    Type I interferons (IFN-I) have long been heralded as key contributors to effective antiviral responses. More widely understood in the context of acute viral infection, the role of this pleiotropic cytokine has been characterized as triggering antiviral states in cells and potentiating adaptive immune responses. Upon induction in the innate immune response, IFN-I triggers the expression of interferon-stimulated genes (ISGs), which upregulate the effector function of immune cells (e.g., dendritic cells, B cells, and T cells) toward successful resolution of infections. However, emerging lines of evidence reveal that viral persistence in the course of chronic infections could be driven by deleterious immunomodulatory effects upon sustained IFN-I expression. In this setting, elevation of IFN-I and ISGs is directly correlated to viral persistence and elevated viral loads. It is important to note that the correlation among IFN-I expression, ISGs, and viral persistence may be a cause or effect of chronic infection and this is an important distinction to make toward establishing the dichotomous nature of IFN-I responses. The aim of this mini review is to (i) summarize the interaction between IFN-I and downstream effector responses and therefore (ii) delineate the function of this cytokine on positive and negative immunoregulation in chronic infection. This is a significant consideration given the current therapeutic administration of IFN-I in chronic viral infections whose therapeutic significance is projected to continue despite emergence of increasingly efficacious antiviral regimens. Furthermore, elucidation of the interplay between virus and the antiviral response in the context of IFN-I will elucidate avenues toward more effective therapeutic and prophylactic measures against chronic viral infections.

  13. Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?

    DEFF Research Database (Denmark)

    Gurusamy, Kurinchi S; Wilson, Edward; Koretz, Ronald L

    2013-01-01

    Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.......Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs....

  14. Early events in the pathogenesis of foot-and-mouth disease in pigs; identification of oropharyngeal tonsils as sites of primary and sustained viral replication.

    Directory of Open Access Journals (Sweden)

    Carolina Stenfeldt

    Full Text Available A time-course study was performed to elucidate the early events of foot-and-mouth disease virus (FMDV infection in pigs subsequent to simulated natural, intra-oropharyngeal, inoculation. The earliest detectable event was primary infection in the lingual and paraepiglottic tonsils at 6 hours post inoculation (hpi characterized by regional localization of viral RNA, viral antigen, and infectious virus. At this time FMDV antigen was localized in cytokeratin-positive epithelial cells and CD172a-expressing leukocytes of the crypt epithelium of the paraepiglottic tonsils. De novo replication of FMDV was first detected in oropharyngeal swab samples at 12 hpi and viremia occurred at 18-24 hpi, approximately 24 hours prior to the appearance of vesicular lesions. From 12 through 78 hpi, microscopic detection of FMDV was consistently localized to cytokeratin-positive cells within morphologically characteristic segments of oropharyngeal tonsil crypt epithelium. During this period, leukocyte populations expressing CD172a, SLA-DQ class II and/or CD8 were found in close proximity to infected epithelial cells, but with little or no co-localization with viral proteins. Similarly, M-cells expressing cytokeratin-18 did not co-localize with FMDV proteins. Intra-epithelial micro-vesicles composed of acantholytic epithelial cells expressing large amounts of structural and non-structural FMDV proteins were present within crypts of the tonsil of the soft palate during peak clinical infection. These findings inculpate the paraepiglottic tonsils as the primary site of FMDV infection in pigs exposed via the gastrointestinal tract. Furthermore, the continuing replication of FMDV in the oropharyngeal tonsils during viremia and peak clinical infection with no concurrent amplification of virus occurring in the lower respiratory tract indicates that these sites are the major source of shedding of FMDV from pigs.

  15. 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

  16. 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 ...

  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. Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Deborah Heydenburg Fuller

    Full Text Available Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT, during antiretroviral therapy (ART induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans.

  19. [Viral superantigens].

    Science.gov (United States)

    Us, Dürdal

    2016-07-01

    , expression of endogenous SAgs leads to thymic deletion of responding T cells (bearing Vβ6-9+ TCR) due to self-tolerance induction during the fetal life, and protects the host against future exogenous MMTV infections. The SAg of rabies virus is the N protein found in nucleocapsid structure and stimulates Vβ8+TCR-bearing T cells. The SAg-induced polyclonal activation of T cells leads to turn-off the specific immune response, to enhance the immunopathogenesis and facilitates viral transmission from the initial site of infection (the muscle tissue) to the nerve endings. In case of EBV-associated SAg that activates Vβ13+TCR-bearing T cells, it was detected that the SAg activity was not encoded by EBV itself, but instead was due to the transactivation of HERV-K18 by EBV latent membrane proteins, whose env gene encodes the SAg (Sutkowski, et al. 2001). It has been denoted that EBV-induced SAg expression plays a role in the long-term persistence and latency of virus in memory B cells, in the development of autoimmune diseases and in the oncogenesis mechanisms. The proteins which are identified as SAgs of HIV are Nef and gp120. It is believed that, the massive activation of CD4+ T cells (selectively with Vβ-12+, Vβ-5.3+ and Vβ-18+ TCRs) in early stages of infection and clonal deletion, anergy and apoptosis of bystander T cells in the late stages may be due to SAg property of Nef protein, as well as the other mechanisms. However there are some studies indicating that Nef does not act as a SAg (Lapatschek, et al. 2001). HIV gp120 glycoprotein is a B-cell SAg that binds to VH3-expressing B cell receptors and causes polyclonal B cell activation. In addition, binding of gp120 to IgE on the surface of basophiles and mast cells causes activation of those cells, secretion of high level proinflammatory mediators leading to allergic reactions and tissue damage. In a recent study, the depletion (anergy or deletion) of T cell populations bearing Vβ12+, Vβ13+ and Vβ17+ TCR have been

  20. RT-PCR em pools de soros sangüíneos para o diagnóstico da infecção aguda e de animais persistentemente infectados pelo vírus da diarréia viral bovina RT-PCR in pools of bovine blood serum to detect acute infection and persistently infected animals with bovine viral diarrhea virus

    Directory of Open Access Journals (Sweden)

    D. Pilz

    2007-02-01

    Full Text Available Utilizou-se a técnica da RT-PCR para a detecção da região 5' UTR do genoma do vírus da diarréia viral bovina (BVDV em pools de soros sangüíneos provenientes de um rebanho, constituído por 226 animais, que apresentava distúrbios da reprodução. A partir das amostras individuais de soro e de acordo com a categoria dos animais e o número de animais por categoria foram formados 10 pools (A a J de soros. A primeira avaliação revelou a amplificação de um produto com 290pb nas reações referentes aos grupos D (35 vacas e H (25 bezerros lactentes que, após o desmembramento em amostras individuais, resultou na identificação de 11 vacas lactantes e 12 bezerros em amamentação positivos. Para a identificação de animais persistentemente infectados (PI entre os 23 positivos na primeira avaliação, realizou-se a segunda colheita de soros sangüíneos, três meses após. A RT-PCR das amostras individuais de soro revelou resultado positivo em cinco bezerros. Em dois, foi possível isolar o BVDV em cultivo de células MDBK. A especificidade das reações da RT-PCR foi confirmada pelo seqüenciamento dos produtos amplificados a partir do soro de uma vaca com infecção aguda, de um bezerro PI e das duas amostras do BVDV isoladas em cultivo celular. A utilização da RT-PCR em pools de soros sangüíneos demonstrou ser uma estratégia rápida de diagnóstico etiológico e de baixo custo tanto para a detecção de infecção aguda quanto de animais PI.The 5' untranslated region of the bovine viral diarrhea virus (BVDV genome was detected by RT-PCR assay in pools of blood sera samples collected from a cattle herd (n=226 animals with reproductive failures. Based on the classes of animal and the number of animals per class, the individual blood serum samples were distributed in 10 sera pools (A to J. During the first evaluation a 290bp amplicon was amplified in reactions from groups D (35 cows and H (25 sucking calves. The individual analysis

  1. 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

  2. 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.

  3. Influence of sustained viral response on the regression of fibrosis and portal hypertension in cirrhotic HCV patients treated with antiviral triple therapy

    Directory of Open Access Journals (Sweden)

    Ángela Puente

    Full Text Available Background and aims: The regression of liver fibrosis and portal hypertension (PH and their influence on the natural history of compensated hepatitis C virus (HCV-related cirrhosis has not been studied previously. Our objective was to evaluate the influence of sustained virologic response (SVR on the portal pressure gradient (HVPG and non-invasive parameters of PH and prognostic factors of response. Methods: Sixteen patients with compensated HCV genotype 1-related cirrhosis with PH (HVPG > 6 mmHg without beta-blocker therapy were considered as candidates for PEGα2a + RBV + BOC (48 weeks; lead-in and accepted stopping rules. A hemodynamic study and Fibroscan® were performed at baseline, at eight weeks and, in the case of SVR, 24 weeks after treatment. In each hemodynamic study, serum samples were analyzed for inflammatory biomarkers associated with PH. Results: In eight cases, SVR was obtained; five patients relapsed, and treatment was stopped early for non-response to lead in (one case and a decrease of < 3 log at week 8 (two patients. Compared to baseline, there was a significant decrease in HVPG and Fibroscan® at weeks 8 and 72 (10.31 ± 4.3 vs 9.4 ± 5.04 vs 6.1 ± 3.61 mmHg, p < 0.0001 and 21.3 ± 14.5 vs 16.2 ± 9.5 vs 6.4 ± 4.5 kPa, p < 0.0001, respectively. The average HVPG decrease in SVR was 40.8 ± 17.53%, achieving an HVPG < 6 mmHg in five patients (62.5% and a Fibroscan® < 7.1 kPa in three patients (37.5%. Conclusions: Complete hemodynamic response (HVPG < 6 mmHg and fibrosis regression (Fibroscan® < 7.1 kPa occur in more than half and one-third of patients achieving SVR, respectively, and must be another target in cirrhotic patients with SVR.

  4. Influence of sustained viral response on the regression of fibrosis and portal hypertension in cirrhotic HCV patients treated with antiviral triple therapy.

    Science.gov (United States)

    Puente, Ángela; Cabezas, Joaquín; López Arias, María Jesús; Fortea, José Ignacio; Arias, María Teresa; Estébanez, Ángel; Casafont, Fernando; Fábrega, Emilio; Crespo, Javier

    2017-01-01

    The regression of liver fibrosis and portal hypertension (PH) and their influence on the natural history of compensated hepatitis C virus (HCV)-related cirrhosis has not been studied previously. Our objective was to evaluate the influence of sustained virologic response (SVR) on the portal pressure gradient (HVPG) and non-invasive parameters of PH and prognostic factors of response. Sixteen patients with compensated HCV genotype 1-related cirrhosis with PH (HVPG > 6 mmHg) without beta-blocker therapy were considered as candidates for PEGα2a + RBV + BOC (48 weeks; lead-in and accepted stopping rules). A hemodynamic study and Fibroscan® were performed at baseline, at eight weeks and, in the case of SVR, 24 weeks after treatment. In each hemodynamic study, serum samples were analyzed for inflammatory biomarkers associated with PH. In eight cases, SVR was obtained; five patients relapsed, and treatment was stopped early for non-response to lead in (one case) and a decrease of < 3 log at week 8 (two patients). Compared to baseline, there was a significant decrease in HVPG and Fibroscan® at weeks 8 and 72 (10.31 ± 4.3 vs 9.4 ± 5.04 vs 6.1 ± 3.61 mmHg, p < 0.0001 and 21.3 ± 14.5 vs 16.2 ± 9.5 vs 6.4 ± 4.5 kPa, p < 0.0001, respectively). The average HVPG decrease in SVR was 40.8 ± 17.53%, achieving an HVPG < 6 mmHg in five patients (62.5%) and a Fibroscan® < 7.1 kPa in three patients (37.5%). Complete hemodynamic response (HVPG < 6 mmHg) and fibrosis regression (Fibroscan® < 7.1 kPa) occur in more than half and one-third of patients achieving SVR, respectively, and must be another target in cirrhotic patients with SVR.

  5. Targeting Persistent Human Papillomavirus Infection.

    Science.gov (United States)

    Shanmugasundaram, Srinidhi; You, Jianxin

    2017-08-18

    While the majority of Human papillomavirus (HPV) infections are transient and cleared within a couple of years following exposure, 10-20% of infections persist latently, leading to disease progression and, ultimately, various forms of invasive cancer. Despite the clinical efficiency of recently developed multivalent prophylactic HPV vaccines, these preventive measures are not effective against pre-existing infection. Additionally, considering that the burden associated with HPV is greatest in regions with limited access to preventative vaccination, the development of effective therapies targeting persistent infection remains imperative. This review discusses not only the mechanisms underlying persistent HPV infection, but also the promise of immunomodulatory therapeutic vaccines and small-molecular inhibitors, which aim to augment the host immune response against the viral infection as well as obstruct critical viral-host interactions.

  6. CTL Escape and Viral Fitness in HIV/SIV Infection.

    Science.gov (United States)

    Seki, Sayuri; Matano, Tetsuro

    2011-01-01

    Cytotoxic T lymphocyte (CTL) responses exert a suppressive effect on HIV and simian immunodeficiency virus (SIV) replication. Under the CTL pressure, viral CTL escape mutations are frequently selected with viral fitness costs. Viruses with such CTL escape mutations often need additional viral genome mutations for recovery of viral fitness. Persistent HIV/SIV infection sometimes shows replacement of a CTL escape mutation with an alternative escape mutation toward higher viral fitness. Thus, multiple viral genome changes under CTL pressure are observed in the chronic phase of HIV/SIV infection. HIV/SIV transmission to HLA/MHC-mismatched hosts drives further viral genome changes including additional CTL escape mutations and reversions under different CTL pressure. Understanding of viral structure/function and host CTL responses would contribute to prediction of HIV evolution and control of HIV prevalence.

  7. What is the impact of a country-wide scale-up in antiviral therapy on the characteristics and sustained viral response rates of patients treated for hepatitis C?

    Science.gov (United States)

    McDonald, Scott A; Innes, Hamish A; Hayes, Peter C; Dillon, John F; Mills, Peter R; Goldberg, David J; Barclay, Stephen; Allen, Sam; Fox, Ray; Fraser, Andrew; Kennedy, Nicholas; Bhattacharyya, Diptendu; Hutchinson, Sharon J

    2015-02-01

    The global burden associated with hepatitis C virus (HCV) infection has prompted a scale-up of antiviral therapy. Hitherto, no data exist on the impact of scaling-up, on the characteristics of treated populations, or on sustained viral response (SVR) rates. We assessed the country-wide scale-up of antiviral therapy in Scotland, a country which nationally monitors uptake of and response to HCV treatment. Data for patients, initiated on combined pegylated interferon and ribavirin therapy at 13 specialist HCV clinics in 2001-2010, were extracted from the Scottish HCV Clinical Database (n=3895). Patient characteristics included age, genotype, PWID (people who inject drugs) status, prison referral, and diagnosed cirrhosis. Temporal trends in covariates and adjusted effects on a SVR were examined via mixed-effects regression. The number of patients starting treatment increased from 237 in 2001-2002 to 1560 in 2009-2010, with an increasing trend in SVR from 44% to 57% over this period. For a given clinic, between 2001/2 and 2010 there was a decrease in the odds of those treated being diagnosed with cirrhosis (odds ratio [OR]=0.84 per year), and increasing temporal trends for those treated being PWID (OR=1.08) and prison referrals (OR=1.06). Adjusting for covariates, the proportion of a given clinic's patients achieving SVR was positively associated with the percentage of PWID (OR=1.01 per percent increase; 95% confidence interval [CI]: 1.00-1.02) and genotype 2/3 (OR=1.03; 95% CI: 1.02-1.04). Despite changes in patient characteristics, a country-wide scale-up of antiviral therapy did not compromise SVR rates. Results are highly relevant to countries planning on scaling-up treatment, given the forthcoming availability of new interferon-free therapies. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  8. Negative regulation of type I IFN expression by OASL1 permits chronic viral infection and CD8⁺ T-cell exhaustion.

    Directory of Open Access Journals (Sweden)

    Myeong Sup Lee

    Full Text Available The type I interferons (IFN-Is are critical not only in early viral control but also in prolonged T-cell immune responses. However, chronic viral infections such as those of human immunodeficiency virus (HIV and hepatitis C virus (HCV in humans and lymphocytic choriomeningitis virus (LCMV in mice overcome this early IFN-I barrier and induce viral persistence and exhaustion of T-cell function. Although various T-cell-intrinsic and -extrinsic factors are known to contribute to induction of chronic conditions, the roles of IFN-I negative regulators in chronic viral infections have been largely unexplored. Herein, we explored whether 2'-5' oligoadenylate synthetase-like 1 (OASL1, a recently defined IFN-I negative regulator, plays a key role in the virus-specific T-cell response and viral defense against chronic LCMV. To this end, we infected Oasl1 knockout and wild-type mice with LCMV CL-13 (a chronic virus and monitored T-cell responses, serum cytokine levels, and viral titers. LCMV CL-13-infected Oasl1 KO mice displayed a sustained level of serum IFN-I, which was primarily produced by splenic plasmacytoid dendritic cells, during the very early phase of infection (2-3 days post-infection. Oasl1 deficiency also led to the accelerated elimination of viremia and induction of a functional antiviral CD8 T-cell response, which critically depended on IFN-I receptor signaling. Together, these results demonstrate that OASL1-mediated negative regulation of IFN-I production at an early phase of infection permits viral persistence and suppresses T-cell function, suggesting that IFN-I negative regulators, including OASL1, could be exciting new targets for preventing chronic viral infection.

  9. Protection from persistent infection with a bovine viral diarrhea virus (BVDV) type 1b strain by a modified-live vaccine containing BVDV types 1a and 2, infectious bovine rhinotracheitis virus, parainfluenza 3 virus and bovine respiratory syncytial virus.

    Science.gov (United States)

    Xue, Wenzhi; Mattick, Debra; Smith, Linda

    2011-06-24

    Recent studies showed that BVDV-1b subgenotype is dominant in North and South American field BVDV isolates. However, nearly all commercially available BVDV-1 vaccines contain BVDV-1a strains. In order to study the efficacy of BVDV-1a vaccine against BVDV-1b infection, this study was designed to evaluate a modified-live vaccine (MLV) containing BVDV-1a and BVDV-2 strains for its efficacy in prevention of persistent infection of fetuses against BVDV-1b strain, when the heifers were vaccinated prior to breeding. Heifers were vaccinated subcutaneously with a single dose of the MLV and bred four weeks after vaccination. The pregnant heifers were challenged with a non-cytopathic BVDV-1b strain at approximately 80 days of gestation. Vaccinated heifers were protected from clinical disease and viremia caused by the BVDV-1b virus. At approximately 155 days of gestation, the fetuses were harvested and tissue samples of thymus, lungs, spleen, kidney and intestines were collected for virus isolation. BVDV was isolated from 100% of the fetuses in the non-vaccinated control group, and from only one fetus (4.3%) from the vaccinated group. Results demonstrated that the MLV containing BVDV-1a and BVDV-2 strains provided 96% protection from fetal persistent infection caused by the BVDV-1b strain. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Persistent Modelling

    DEFF Research Database (Denmark)

    2012-01-01

    The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident...... characteristic of architectural practice. But the persistence in persistent modelling can also be understood to apply in other ways, reflecting and anticipating extended roles for representation. This book identifies three principle areas in which these extensions are becoming apparent within contemporary....... It also provides critical insight into the use of contemporary modelling tools and methods, together with an examination of the implications their use has within the territories of architectural design, realisation and experience....

  12. Persistent Modelling

    DEFF Research Database (Denmark)

    2012-01-01

    The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident....... It also provides critical insight into the use of contemporary modelling tools and methods, together with an examination of the implications their use has within the territories of architectural design, realisation and experience....... characteristic of architectural practice. But the persistence in persistent modelling can also be understood to apply in other ways, reflecting and anticipating extended roles for representation. This book identifies three principle areas in which these extensions are becoming apparent within contemporary...

  13. The case for viral load testing in adolescents in resource-limited settings.

    Science.gov (United States)

    Marcus, Rebecca; Ferrand, Rashida A; Kranzer, Katharina; Bekker, Linda-Gail

    2017-11-01

    The success of HIV treatment programmes globally has resulted in children with perinatally acquired HIV reaching adolescence in large numbers. The number of adolescents living with HIV is growing further due to persisting high HIV incidence rates among adolescents in low- and middle-income settings, particularly in sub-Saharan Africa. Although expanding access to HIV viral load monitoring is necessary to achieve the 90-90-90 targets across the HIV care continuum, implementation is incomplete. We discuss the rationale for prioritizing viral load monitoring among adolescents and the associated challenges. Adolescents with HIV are a complex group to treat successfully due to extensive exposure to antiretroviral therapy for those with perinatally acquired HIV and the challenges in sustained medication adherence in this age group. Given the high risk of treatment failure among adolescents and the limited drug regimens available in limited resource settings, HIV viral load monitoring in adolescents could prevent unnecessary and costly switches to second-line therapy in virologically suppressed adolescents. Because adolescents living with HIV may be heavily treatment experienced, have suboptimal treatment adherence, or may be on second or even third-line therapy, viral load testing would allow clinicians to make informed decisions about increased counselling and support for adolescents together with the need to maintain or switch therapeutic regimens. Given scarce resources, prioritization of viral load testing among groups with a high risk of virological failure may be required. Adolescents have disproportionately high rates of virological failure, and targeting this age group for viral load monitoring may provide valuable lessons to inform broader scale-up. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

  14. Persistence theory

    CERN Document Server

    Oudot, Steve Y

    2015-01-01

    Persistence theory emerged in the early 2000s as a new theory in the area of applied and computational topology. This book provides a broad and modern view of the subject, including its algebraic, topological, and algorithmic aspects. It also elaborates on applications in data analysis. The level of detail of the exposition has been set so as to keep a survey style, while providing sufficient insights into the proofs so the reader can understand the mechanisms at work. The book is organized into three parts. The first part is dedicated to the foundations of persistence and emphasizes its conne

  15. Persistent angina

    DEFF Research Database (Denmark)

    Jespersen, Lasse; Abildstrøm, Steen Z; Hvelplund, Anders

    2013-01-01

    AIMS: To evaluate persistent angina in stable angina pectoris with no obstructive coronary artery disease (CAD) compared to obstructive CAD and its relation to long-term anxiety, depression, quality of life (QOL), and physical functioning. METHODS AND RESULTS: We invited 357 patients (men = 191...

  16. Habit persistence

    DEFF Research Database (Denmark)

    Vinther Møller, Stig

    2009-01-01

    This paper uses an iterated GMM approach to estimate and test the consumption based habit persistence model of Campbell and Cochrane (1999) on the US stock market. The empirical evidence shows that the model is able to explain the size premium, but fails to explain the value premium. Further...

  17. Semibiotic Persistence

    Science.gov (United States)

    Prothmann, C.; Zauner, K.-P.

    From observation, we find four different strategies to successfully enable structures to persist over extended periods of time. If functionally relevant features are very large compared to the changes that can be effectuated by entropy, the functional structure itself has a high enough probability to erode only slowly over time. If the functionally relevant features are protected from environmental influence by sacrificial layers that absorb the impinging of the environment, deterioration can be avoided or slowed. Loss of functionality can be delayed, even for complex systems, by keeping alternate options for all required components available. Biological systems also apply information processing to actively counter the impact of entropy by mechanisms such as self-repair. The latter strategy increases the overall persistence of living systems and enables them to maintain a highly complex functional organisation during their lifetime and over generations. In contrast to the other strategies, information processing has only low material overhead. While at present engineered technology is far from achieving the self-repair of evolved systems, the semibiotic combination of biological components with conventionally engineered systems may open a path to long-term persistence of functional devices in harsh environments. We review nature's strategies for persistence, and consider early steps taken in the laboratory to import such capabilities into engineered architectures.

  18. Viral lysis of

    NARCIS (Netherlands)

    Lønborg, C.; Middelboe, M.; Brussaard, C.P.D.

    2013-01-01

    The viral mediated transformation of phytoplankton organic carbon to dissolved forms (“viral shunt”) has been suggested as a major source of dissolved organic carbon (DOC) in marine systems. Despite the potential implications of viral activity on the global carbon fluxes, studies investigating

  19. Viral Marketing Past Present Future

    OpenAIRE

    Nessipbekova, Zarina

    2010-01-01

    The work studies the viral marketing. These are past viral campaigns, viral campaigns today, and evaluates their actuality. The work tries to predict the development of viral marketing on the basis of the research done by the author.

  20. Poliovirus persistence in human cells in vitro.

    Science.gov (United States)

    Colbère-Garapin, F; Jacques, S; Drillet, A S; Pavio, N; Couderc, T; Blondel, B; Pelletier, I

    2001-01-01

    Poliovirus (PV) can persist in vivo in the intestine of immunocompromised hosts for years. Moreover, immunocompetent individuals who have survived paralytic poliomyelitis sometimes develop the post-poliomyelitis syndrome (PPS), consisting of a variety of symptoms including new muscular atrophies. PPS may be due to PV persistence. We have developed models of PV persistence in neural cells and epidermoid cells. Cell determinants are of crucial importance for the establishment of persistent infections in human neuronal cells, whereas viral determinants play the primary role in human epidermoid HEp-2 cells. The results obtained with these in vitro models show the capacity of PV to persist and reveal a virus and cell co-evolution involving PV-receptor interactions. In addition, they suggest that several mechanisms are used by PV to establish and maintain persistent infections.

  1. APOBEC3 Interference during Replication of Viral Genomes

    Directory of Open Access Journals (Sweden)

    Luc Willems

    2015-06-01

    Full Text Available Co-evolution of viruses and their hosts has reached a fragile and dynamic equilibrium that allows viral persistence, replication and transmission. In response, infected hosts have developed strategies of defense that counteract the deleterious effects of viral infections. In particular, single-strand DNA editing by Apolipoprotein B Editing Catalytic subunits proteins 3 (APOBEC3s is a well-conserved mechanism of mammalian innate immunity that mutates and inactivates viral genomes. In this review, we describe the mechanisms of APOBEC3 editing during viral replication, the viral strategies that prevent APOBEC3 activity and the consequences of APOBEC3 modulation on viral fitness and host genome integrity. Understanding the mechanisms involved reveals new prospects for therapeutic intervention.

  2. Viral Entry into Cells

    Science.gov (United States)

    D'Orsogna, Maria R.

    2010-09-01

    Successful viral infection of a healthy cell requires complex host-pathogen interactions. In this talk we focus on the dynamics specific to the HIV virus entering a eucaryotic cell. We model viral entry as a stochastic engagement of receptors and coreceptors on the cell surface. We also consider the transport of virus material to the cell nucleus by coupling microtubular motion to the concurrent biochemical transformations that render the viral material competent for nuclear entry. We discuss both mathematical and biological consequences of our model, such as the formulation of an effective integrodifferential boundary condition embodying a memory kernel and optimal timing in maximizing viral probabilities.

  3. Persistent Modelling

    DEFF Research Database (Denmark)

    2012-01-01

    The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident....... It also provides critical insight into the use of contemporary modelling tools and methods, together with an examination of the implications their use has within the territories of architectural design, realisation and experience....... on this subject, this book makes essential reading for anyone considering new ways of thinking about architecture. In drawing upon both historical and contemporary perspectives this book provides evidence of the ways in which relations between representation and the represented continue to be reconsidered...

  4. Exergy sustainability.

    Energy Technology Data Exchange (ETDEWEB)

    Robinett, Rush D. III (.; ); Wilson, David Gerald; Reed, Alfred W.

    2006-05-01

    Exergy is the elixir of life. Exergy is that portion of energy available to do work. Elixir is defined as a substance held capable of prolonging life indefinitely, which implies sustainability of life. In terms of mathematics and engineering, exergy sustainability is defined as the continuous compensation of irreversible entropy production in an open system with an impedance and capacity-matched persistent exergy source. Irreversible and nonequilibrium thermodynamic concepts are combined with self-organizing systems theories as well as nonlinear control and stability analyses to explain this definition. In particular, this paper provides a missing link in the analysis of self-organizing systems: a tie between irreversible thermodynamics and Hamiltonian systems. As a result of this work, the concept of ''on the edge of chaos'' is formulated as a set of necessary and sufficient conditions for stability and performance of sustainable systems. This interplay between exergy rate and irreversible entropy production rate can be described as Yin and Yang control: the dialectic synthesis of opposing power flows. In addition, exergy is shown to be a fundamental driver and necessary input for sustainable systems, since exergy input in the form of power is a single point of failure for self-organizing, adaptable systems.

  5. Viral Haemorrhagic Septicaemia Virus

    DEFF Research Database (Denmark)

    Olesen, Niels Jørgen; Skall, Helle Frank

    2013-01-01

    This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus.......This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus....

  6. Novel viral translation strategies.

    Science.gov (United States)

    Au, Hilda H T; Jan, Eric

    2014-01-01

    Viral genomes are compact and encode a limited number of proteins. Because they do not encode components of the translational machinery, viruses exhibit an absolute dependence on the host ribosome and factors for viral messenger RNA (mRNA) translation. In order to recruit the host ribosome, viruses have evolved unique strategies to either outcompete cellular transcripts that are efficiently translated by the canonical translation pathway or to reroute translation factors and ribosomes to the viral genome. Furthermore, viruses must evade host antiviral responses and escape immune surveillance. This review focuses on some recent major findings that have revealed unconventional strategies that viruses utilize, which include usurping the host translational machinery, modulating canonical translation initiation factors to specifically enhance or repress overall translation for the purpose of viral production, and increasing viral coding capacity. The discovery of these diverse viral strategies has provided insights into additional translational control mechanisms and into the viral host interactions that ensure viral protein synthesis and replication. © 2014 John Wiley & Sons, Ltd.

  7. 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.

  8. Viral marketing on the Internet

    OpenAIRE

    Štverák, Martin

    2008-01-01

    Thesis provides an overview of viral marketing. It describes the process by which you can be inspired to implement viral campaign. The thesis includes analysis of specific viral Web project. The aim of this thesis is to create a breakdown of the various components of viral marketing, to establish conditions that should be satisfied for the viral marketing to success, suggesting how to use viral marketing on social network Facebook and evaluate the various components of this service for the pr...

  9. Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia.

    Science.gov (United States)

    Ho, G Y; Burk, R D; Klein, S; Kadish, A S; Chang, C J; Palan, P; Basu, J; Tachezy, R; Lewis, R; Romney, S

    1995-09-20

    Cervical dysplasia, also referred to as squamous intraepithelial lesion (SIL) in cytology or cervical intraepithelial neoplasia in histopathology, is thought to have the potential to advance in progressive stages to cervical cancer. However, not all cases of SIL progress, and most of the mild lesions spontaneously regress. Factors that govern regression, persistence, and progression of SIL are poorly understood. Our analysis sought to identify factors that determined persistence or regression of SIL. Seventy subjects with histopathologically confirmed cervical dysplasia were followed at 3-month intervals for 15 months. At each visit, the cervix was evaluated by Pap smear and colposcopy, and exfoliated cervicovaginal cells were analyzed for human papillomavirus (HPV) DNA. For each subject, data from every two consecutive visits were grouped as a pair. Persistent SIL was considered present if a lesion was detected at a visit (t) as well as at the next visit (t + 1) and absent if a lesion was detected at visit t but not at visit t + 1. A statistical model for time-dependent data correlated persistent SIL with various risk factors. Age, ethnicity, education, sexual behavior, smoking, and the use of oral contraceptives did not correlate with persistent SIL. The risk of persistent SIL was associated with continual HPV infection in visits t and t + 1 (HPV positive by Southern blot analysis: odds ratio [OR] = 3.91, and 95% confidence interval [CI] = 1.58-9.65; HPV positive by polymerase chain reaction [PCR]: OR = 2.42, and 95% CI = 1.03-5.67) and a persistent high viral load (OR = 4.07, and 95% CI = 1.35-12.30). When typed by PCR, individuals with type-specific persistent infection in visits t and t + 1, and particularly those with a continual high viral load (OR = 4.97; 95% CI = 1.45-17.02), had the highest risk for persistent SIL compared with those with a low level of type-specific persistent infection or non-type-specific persistent infection. The presence of

  10. SUMO Ubc9 enzyme as a viral target.

    Science.gov (United States)

    Varadaraj, Archana; Mattoscio, Domenico; Chiocca, Susanna

    2014-01-01

    Viruses alter specific host cell targets to counteract possible defense mechanisms aimed at eliminating infectivity and viral propagation. The SUMO conjugating enzyme Ubc9 functions as a hub for protein sumoylation, whilst also providing an interactive surface for sumoylated proteins through noncovalent interactions. The targeting of Ubc9 by viruses and viral proteins is thus highly beneficial for the disruption of both protein modification and protein-protein interaction mechanisms with which proteins increase their functional repertoire in cells. This review explores some of the clever mechanisms adopted by viruses to deregulate Ubc9, influence effector pathways and positively impact viral persistence consequently. © 2014 International Union of Biochemistry and Molecular Biology.

  11. Sequeale of acute viral hepatitis type B.

    Science.gov (United States)

    Lesnicar, J; Ferluga, D; Lesnicar, G

    1977-08-01

    In 1976 we undertook to evaluate the incidence of chronic liver lesions in 161 patients treated in hospital during the years 1970-1975 for their serologically established acute viral hepatitis type B (AVH-B). At systematic control examination mode in 1976, after a period from 1-5 years since the acute onset of disease, it was established that in 133 individuals (82.6%) the antigen HBs had disappeared from blood and the BLT had become normal. Persistent HBs antigenemia was established in 20 (12.4%) individuals. In 15 (9.2%) patients persistent HBs antigenemia was accompanied by pathologic BLT, in 5 (3.1%) cases liver function became returned to normal yet with the persistent HBs antigenemia after their recovery from A VH-B. In 8 (4.9%) patients pathologic BLT persisted although HBsAg had disappeared from blood. Among 28 persons with persistent pathological BLT or with persistent HBs antigenemia out of a total of 161 patients who had had A VH-B, there were 11 (6.8%) cases with the bioptically proved CPHf, 8 (5.0%) cases with CPH, 5 (3.1%) cases with CAH, while 4 (2.5%) patients showed fatty liver metamorphosis or had by light microskopy completely normal liver. CAH was established only in cases with persistent BHs antigenemia and pathological BLT. The incidence of the chronic liver lesion and of the persistent antigenemia was among our patients who had had A VH-B in inverse ratio to the intensity of their initial infection. Our study suggests that no prodisposition for persistent HBs antigenemia is created by the prednisolone therapy.

  12. Viral pathogenesis in diagrams

    National Research Council Canada - National Science Library

    Tremblay, Michel; Berthiaume, Laurent; Ackermann, Hans-Wolfgang

    2001-01-01

    .... The 268 diagrams in Viral Pathogenesis in Diagrams were selected from over 800 diagrams of English and French virological literature, including one derived from a famous drawing by Leonardo da Vinci...

  13. Viral Gastroenteritis (Stomach Flu)

    Science.gov (United States)

    ... 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- ...

  14. Viral hemorrhagic septicemia

    Science.gov (United States)

    Batts, William N.; Winton, James R.

    2012-01-01

    Viral hemorrhagic septicemia (VHS) is one of the most important viral diseases of finfish worldwide. In the past, VHS was thought to affect mainly rainbow trout Oncorhynchus mykiss reared at freshwater facilities in Western Europe where it was known by various names including Egtved disease and infectious kidney swelling and liver degeneration (Wolf 1988). Today, VHS is known as an important source of mortality for cultured and wild fish in freshwater and marine environments in several regions of the northern hemisphere (Dixon 1999; Gagné et al. 2007; Kim and Faisal 2011; Lumsden et al. 2007; Marty et al. 1998, 2003; Meyers and Winton 1995; Skall et al. 2005b; Smail 1999; Takano et al. 2001). Viral hemorrhagic septicemia is caused by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), a member of the genus Novirhabdovirus of the family Rhabdoviridae

  15. HIV Viral Load

    Science.gov (United States)

    ... Chains Sex Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle ... used each time. Will exercise, nutrition, and other lifestyle modifications help decrease my HIV viral load? There ...

  16. Treatment of viral encephalitis.

    Science.gov (United States)

    Domingues, Renan Barros

    2009-03-01

    Several viruses may cause central nervous system diseases with a broad range of clinical manifestations. The time course of the viral encephalitis can be acute, subacute, or chronic. Pathologically there are encephalitis with direct viral entry into the CNS in which brain parenchyma exhibits neuronal damaging and viral antigens and there are postinfectious autoimmune encephalitis associated with systemic viral infections with brain tissue presenting perivascular aggregation of immune cells and myelin damaging. Some virus affect previously healthy individuals while others produce encephalitis among imunocompromised ones. Factors such evolving lifestyles and ecological changes have had a considerable impact on the epidemiology of some viral encephalitis [e.g. West-Nile virus, and Japanese B virus]. Citomegalovirus and JC virus are examples of infections of the brain that have been seen more frequently because they occur in immunocompromised patients. In the other hand many scientific achievements in neuroimaging, molecular diagnosis, antiviral therapy, immunomodulatory treatments, and neurointensive care have allowed more precise and earlier diagnoses and more efficient treatments, resulting in improved outcomes. In this article, we will present the current drug options in the management of the main acute and chronic viral infection of the central nervous system of immunocompetent and immunocompromised adults, focusing on drugs mechanisms of action, efficacy, and side effects. The early diagnosis and correct management of such diseases can reduce mortality and neurological sequelae; however, even with recent treatment advances, potentially devastating outcomes are still possible.

  17. Conditions for viral influence spreading through correlated multiplex networks

    CERN Document Server

    Hu, Yanqing; Makse, Hernán A

    2014-01-01

    A fundamental problem in network science is to predict how certain individuals are able to initiate new networks to spring up ``new ideas''. Frequently, these changes in trends are triggered by a few innovators who rapidly impose their ideas through ``viral'' influence spreading producing cascades of followers fragmenting an old network to create a new one. Typical examples include the raise of scientific ideas or abrupt changes in social media, like the raise of Facebook.com to the detriment of Myspace.com. How this process arises in practice has not been conclusively demonstrated. Here, we show that a condition for sustaining a viral spreading process is the existence of a multiplex correlated graph with hidden ``influence links''. Analytical solutions predict percolation phase transitions, either abrupt or continuous, where networks are disintegrated through viral cascades of followers as in empirical data. Our modeling predicts the strict conditions to sustain a large viral spreading via a scaling form of...

  18. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

    The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

  19. VIRAL DISEASES IN SEA FISH

    OpenAIRE

    Ivančica Strunjak-Perović; Mato Hacmanjek; Rozelinda Čož-Rakovac; Emin Teskeredžić

    1996-01-01

    Adequate knowledge on fish diseases caused by viruses is still lacking. Up until now, in fish which live their entire life cycle or part of it in the sea, some viral diseases have been determined (lymphoeytis, viral necrosis of crythrocytes, ciravosti cod syndrome, encephalitis, viral hemoragic septichemistry, viral hematopoetic necrosis, viral gusteraca necrosis, chum renviral infection, branchionephritis, rabdociral eel infection). Some of these diseases primarily occur in the freshwater ph...

  20. Severe acute respiratory syndrome coronavirus persistence in Vero cells.

    Science.gov (United States)

    Palacios, Gustavo; Jabado, Omar; Renwick, Neil; Briese, Thomas; Lipkin, W Ian

    2005-03-20

    Several coronaviruses establish persistent infections in vitro and in vivo, however it is unknown whether persistence is a feature of the severe acute respiratory syndrome coronavirus (SARS-CoV) life cycle. This study was conducted to investigate viral persistence. We inoculated confluent monolayers of Vero cells with SARS-CoV at a multiplicity of infection of 0.1 TCID50 and passaged the remaining cells every 4 to 8 days for a total of 11 passages. Virus was titrated at each passage by limited dilution assay and nucleocapsid antigen was detected by Western blot and immunofluoresence assays. The presence of viral particles in passage 11 cells was assessed by electron microscopy. Changes in viral genomic sequences during persistent infection were examined by DNA sequencing. Cytopathic effect was extensive after initial inoculation but diminished with serial passages. Infectious virus was detected after each passage and viral growth curves were identical for parental virus stock and virus obtained from passage 11 cells. Nucleocapsid antigen was detected in the majority of cells after initial inoculation but in only 10%-40% of cells at passages 2-11. Electron microscopy confirmed the presence of viral particles in passage 11 cells. Sequence analysis at passage 11 revealed fixed mutations in the spike (S) gene and ORFs 7a-8b but not in the nucleocapsid (N) gene. SARS-CoV can establish a persistent infection in vitro. The mechanism for viral persistence is consistent with the formation of a carrier culture whereby a limited number of cells are infected with each round of virus replication and release. Persistence is associated with selected mutations in the SARS-CoV genome. This model may provide insight into SARS-related lung pathology and mechanisms by which humans and animals can serve as reservoirs for infection.

  1. [Vasculitis and viral infection].

    Science.gov (United States)

    Martínez Aguilar, N E; Guido Bayardo, R; Vargas Camaño, M E; Compañ González, D; Miranda Feria, A J

    1997-01-01

    Viruses have been implicated in vasculitis. To determine activity of viral infection associated with vasculitis. 17 patients with vasculitis had been in immunological and antiviral antibodies evaluation. Twenty five healthy controls sex and age matched with hematic biometry (BH) and AA. All subjects were negative to HIV and HBV. Viral activity was demonstrated in eight patients; vascular purpura (5), Takayasu disease (1), polyarteritis nodosa (1), erythema nodosum (1). None subject of control group had IgM activity. Antibodies response of IgG in patients were of lesser intensity than in control group. 14 abnormalities in BH were found in patients and 4 in control group. Immune response in patients, measured by lymphocyte subpopulations and circulating immune complexes was abnormal. In conclusion 47% showed viral activity, but the dominant feature was abnormal immune response in 82%.

  2. Modeling Viral Capsid Assembly

    Science.gov (United States)

    2014-01-01

    I present a review of the theoretical and computational methodologies that have been used to model the assembly of viral capsids. I discuss the capabilities and limitations of approaches ranging from equilibrium continuum theories to molecular dynamics simulations, and I give an overview of some of the important conclusions about virus assembly that have resulted from these modeling efforts. Topics include the assembly of empty viral shells, assembly around single-stranded nucleic acids to form viral particles, and assembly around synthetic polymers or charged nanoparticles for nanotechnology or biomedical applications. I present some examples in which modeling efforts have promoted experimental breakthroughs, as well as directions in which the connection between modeling and experiment can be strengthened. PMID:25663722

  3. [Viral hepatitis in travellers].

    Science.gov (United States)

    Abreu, Cândida

    2007-01-01

    Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

  4. Immigration and viral hepatitis.

    Science.gov (United States)

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  5. Viral meningitis and encephalitis.

    Science.gov (United States)

    Tuppeny, Misti

    2013-09-01

    Meningitis is an inflammation of the meninges, whereas encephalitis is inflammation of the parenchymal brain tissue. The single distinguishing element between the 2 diagnoses is the altered state of consciousness, focal deficits, and seizures found in encephalitis. Consequently meningoencephalitis is a term used when both findings are present in the patient. Viral meningitis is not necessarily reported as it is often underdiagnosed, whereas encephalitis cases are on the increase in various areas of North America. Improved imaging and viral diagnostics, as well as enhanced neurocritical care management, have improved patient outcomes to date. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Understanding the Innate Immune Response in Viral Hepatitis : Interferons and NK Cells

    NARCIS (Netherlands)

    R.A. de Groen (Rik)

    2017-01-01

    textabstractHBV and HCV infection are the two leading causes of chronic liver inflammation worldwide, affecting an approximate 370–390 million people. Currently, the viral and immunological mechanisms that underlie either the resolution or persistence of viral hepatitis infections are not fully

  7. Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

    Science.gov (United States)

    Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

    2012-01-01

    Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

  8. Persistent hepatitis virus infection and immune homeostasis

    OpenAIRE

    Zhou, Yun

    2014-01-01

    Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

  9. Autophagy pathway induced by a plant virus facilitates viral spread and transmission by its insect vector.

    Science.gov (United States)

    Chen, Yong; Chen, Qian; Li, Manman; Mao, Qianzhuo; Chen, Hongyan; Wu, Wei; Jia, Dongsheng; Wei, Taiyun

    2017-11-01

    Many viral pathogens are persistently transmitted by insect vectors and cause agricultural or health problems. Generally, an insect vector can use autophagy as an intrinsic antiviral defense mechanism against viral infection. Whether viruses can evolve to exploit autophagy to promote their transmission by insect vectors is still unknown. Here, we show that the autophagic process is triggered by the persistent replication of a plant reovirus, rice gall dwarf virus (RGDV) in cultured leafhopper vector cells and in intact insects, as demonstrated by the appearance of obvious virus-containing double-membrane autophagosomes, conversion of ATG8-I to ATG8-II and increased level of autophagic flux. Such virus-containing autophagosomes seem able to mediate nonlytic viral release from cultured cells or facilitate viral spread in the leafhopper intestine. Applying the autophagy inhibitor 3-methyladenine or silencing the expression of Atg5 significantly decrease viral spread in vitro and in vivo, whereas applying the autophagy inducer rapamycin or silencing the expression of Torc1 facilitate such viral spread. Furthermore, we find that activation of autophagy facilitates efficient viral transmission, whereas inhibiting autophagy blocks viral transmission by its insect vector. Together, these results indicate a plant virus can induce the formation of autophagosomes for carrying virions, thus facilitating viral spread and transmission by its insect vector. We believe that such a role for virus-induced autophagy is common for vector-borne persistent viruses during their transmission by insect vectors.

  10. HIV and Viral Hepatitis

    Science.gov (United States)

    ... get some forms of viral hepatitis the same way you get HIV—through unprotected sexual contact and injection drug use. HAV, which causes a short-term but occasionally severe illness, is usually spread when the virus is ingested from contact with ...

  11. Immigration and viral hepatitis

    NARCIS (Netherlands)

    S. Sharma (Suraj); M. Carballo (Manuel); J.J. Feld (Jordan J.); H.L.A. Janssen (Harry)

    2015-01-01

    textabstractWHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and

  12. VIRAL FEVER WITH THROMBOCYTOPENIA

    OpenAIRE

    Shilpa Anand Hakki

    2017-01-01

    BACKGROUND There is an alarming increase in the incidence of fever with thrombocytopenia especially during monsoon and peri-monsoon period. Infections with protozoa, bacteria and viruses can cause thrombocytopenia with or without disseminated intravascular coagulation. Commonly, dengue, malaria, scrub typhus and other rickettsial infections, meningococci, Leptospira and certain viral infections present as fever with thrombocytopenia. Occasionally, these patients can go on to devel...

  13. Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity.

    Science.gov (United States)

    Nice, Timothy J; Osborne, Lisa C; Tomov, Vesselin T; Artis, David; Wherry, E John; Virgin, Herbert W

    2016-06-01

    In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs) play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV) replicates in dendritic cells (DCs) and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1-/- recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.

  14. Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity.

    Directory of Open Access Journals (Sweden)

    Timothy J Nice

    2016-06-01

    Full Text Available In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV replicates in dendritic cells (DCs and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1-/- recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.

  15. Norovirus Polymerase Fidelity Contributes to Viral Transmission In Vivo

    DEFF Research Database (Denmark)

    Arias Esteban, Armando; Thorne, Lucy; Ghurburrun, Elsa

    2016-01-01

    Intrahost genetic diversity and replication error rates are intricately linked to RNA virus pathogenesis, with alterations in viral polymerase fidelity typically leading to attenuation during infections in vivo. We have previously shown that norovirus intrahost genetic diversity also influences v...... and that maintaining diversity is important for the establishment of infection. This work supports the hypothesis that the reduced polymerase fidelity of the pandemic GII.4 human norovirus isolates may contribute to their global dominance.......Intrahost genetic diversity and replication error rates are intricately linked to RNA virus pathogenesis, with alterations in viral polymerase fidelity typically leading to attenuation during infections in vivo. We have previously shown that norovirus intrahost genetic diversity also influences...... viral pathogenesis using the murine norovirus model, as increasing viral mutation frequency using a mutagenic nucleoside resulted in clearance of a persistent infection in mice. Given the role of replication fidelity and genetic diversity in pathogenesis, we have now investigated whether polymerase...

  16. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2007-01-01

    Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness.......Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness....

  17. Viral Marketing and Academic Institution

    OpenAIRE

    Koktová, Silvie

    2010-01-01

    This bachelor thesis examines modern and constantly developing kind of internet marketing -- the so called viral marketing. It deals with its origin, principle, process, advantages and disadvantages, types of viral marketing and presumptions of creating successful viral campaign. The aim of the theoretical part is especially the understanding of viral marketing as one of the effective instruments of contemporary marketing. In this theoretical part the thesis also elaborates a marketing school...

  18. Rarity and persistence.

    Science.gov (United States)

    Vermeij, Geerat J; Grosberg, Richard K

    2018-01-01

    Rarity is a population characteristic that is usually associated with a high risk of extinction. We argue here, however, that chronically rare species (those with low population densities over many generations across their entire ranges) may have individual-level traits that make populations more resistant to extinction. The major obstacle to persistence at low density is successful fertilisation (union between egg and sperm), and chronically rare species are more likely to survive when (1) fertilisation occurs inside or close to an adult, (2) mate choice involves long-distance signals, (3) adults or their surrogate gamete dispersers are highly mobile, or (4) the two sexes are combined in a single individual. In contrast, external fertilisation and wind- or water-driven passive dispersal of gametes, or sluggish or sedentary adult life habits in the absence of gamete vectors, appear to be incompatible with sustained rarity. We suggest that the documented increase in frequency of these traits among marine genera over geological time could explain observed secular decreases in rates of background extinction. Unanswered questions remain about how common chronic rarity actually is, which traits are consistently associated with chronic rarity, and how chronically rare species are distributed among taxa, and among the world's ecosystems and regions. © 2017 John Wiley & Sons Ltd/CNRS.

  19. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  20. PROFILE OF VIRAL CONJUCTIVITIS

    Directory of Open Access Journals (Sweden)

    Gopal Kishan

    2015-04-01

    Full Text Available INTRODUCTION : Viral conjunctivitis is most commonly seen in the outpatient department. A variety of viruses which are responsible for conjunctival infection , of which Adenovirus is the most common. It is highly contagious during the first 2 weeks of infection. It can cause corneal involvement within 4 - 5 days after the onset of symptoms. Corneal lesions range from SPK (Superficial Punctat e Keratitis to epithelial defects. These corneal lesions may cause intense photophobia and impairment of vision. AIM : To find out the commonest etiological agent , to study the clinical features and complications related to it. METHODOLOGY : This study was carried out prospectively. 100 patients who came to outpatient department between October 2013 to October 2014 were enrolled in the study. All the age groups and both the genders were included. Patients underwent slit lamp examination and were diagnosed cl inically. 25 cases were submitted for Gram staining and Polymerase Chain Reaction (PCR study to know the type of virus and serotype . RESULT : 100 patients were diagnosed with viral conjunctivitis and were kept on follow up. 21percent of patients developed SPK. Adenovirus 8 was found to be more common than other viruses. CONCLUSION : The present study showed Adeno virus to be the most common etiological agent causing viral conjunctivitis and complications like subepithelial opacities and diminished vision

  1. Cell-to-Cell Spread of HIV and Viral Pathogenesis.

    Science.gov (United States)

    Law, K M; Satija, N; Esposito, A M; Chen, B K

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) gives rise to a chronic infection that progressively depletes CD4(+) T lymphocytes. CD4(+) T lymphocytes play a central coordinating role in adaptive cellular and humoral immune responses, and to do so they migrate and interact within lymphoid compartments and at effector sites to mount immune responses. While cell-free virus serves as an excellent prognostic indicator for patient survival, interactions of infected T cells or virus-scavenging immune cells with uninfected T cells can greatly enhance viral spread. HIV can induce interactions between infected and uninfected T cells that are triggered by cell surface expression of viral Env, which serves as a cell adhesion molecule that interacts with CD4 on the target cell, before it acts as the viral membrane fusion protein. These interactions are called virological synapses and promote replication in the face of selective pressure of humoral immune responses and antiretroviral therapy. Other infection-enhancing cell-cell interactions occur between virus-concentrating antigen-presenting cells and recipient T cells, called infectious synapses. The exact roles that these cell-cell interactions play in each stage of infection, from viral acquisition, systemic dissemination, to chronic persistence are still being determined. Infection-promoting immune cell interactions are likely to contribute to viral persistence and enhance the ability of HIV-1 to evade adaptive immune responses. © 2016 Elsevier Inc. All rights reserved.

  2. Persistence of low-pathogenic H5N7 and H7N1 avian influenza subtypes in filtered natural waters

    DEFF Research Database (Denmark)

    Nielsen, Anne Ahlmann; Jensen, Trine Hammer; Stockmarr, Anders

    2013-01-01

    Wild aquatic birds are the natural reservoir of avian influenza virus (AIV), and the virus is transmitted among birds through a fecal-oral route. Infected birds excrete significant amounts of AIV into the environment, and thereby sustain the circulation of AIV in the bird populations. Improved......, which were suspended in filtered natural fresh, brackish or sea water with salinity of 0, 8000 and 20,000 parts per million (ppm), respectively. Also sterilized brackish and sea waters were included in order to examine the influence of microbial flora on virus persistence. All water samples were...... incubated at temperatures representative for seasonal variation of ambient temperatures in Northern Europe (4, 17 and 25°C). The results showed a clear correlation between persistence of viral infectivity and temperature, salinity and presence of microbial flora. While independent of virus subtype...

  3. 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.

  4. Persistence of Change: Fume Hood Campaign Lessons

    Science.gov (United States)

    Feder, Elah; Robinson, Jennifer; Wakefield, Sarah

    2012-01-01

    Purpose: Sustainability initiatives typically operate for a limited time period, but it is often unclear whether they have lasting effects. The purpose of this paper is to examine a laboratory fume hood campaign, in order to identify factors that might contribute or detract from long-term change persistence. Design/methodology/approach: The…

  5. Cytokine mRNA profiles in bronchoalveolar cells of piglets experimentally infected in utero with porcine reproductive and respiratory syndrome virus: Association of sustained expression of IFN-gamma and IL-10 after viral clearance

    DEFF Research Database (Denmark)

    Johnsen, C. K.; Bøtner, Anette; Kamstrup, Søren

    2002-01-01

    An experimental model was used to investigate mRNA cytokine profiles in bronchoalvolar cells (BALC) from piglets, infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV). The BALC's were analyzed for the cytokines TNF-alpha, IFN-gamma, IL-8, IL-10, and IL-12(p40) by real......-time TaqMan polymerase chain reaction in 2-, 4-, and 6-week-old piglets, respectively. High levels of IFN-gamma mRNA was detected in all piglets, while IL-10 was upregulated in 2-week-old piglets, was at normal levels in 4-week-old piglets, and elevated again in 6-week-old piglets. IL-12 was weakly...... elevated in all three age groups. Virus was reduced by 50% in 4-week-old piglets and cleared by 6 weeks of age. The sustained expression of IFNgamma and reduction of IL-10 production indicate an important role for these cytokines in immunity to PRRSV....

  6. Global viral hepatitis elimination by the year 2030

    Directory of Open Access Journals (Sweden)

    Richard Tjan

    2016-12-01

    Full Text Available According to a report by Stanaway et al.(1 in 2016, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. For example, the number of global deaths due to viral hepatitis increased from 0.89 million to 1.45 million, indicating a need for its reduction. In this connection, on 28 May 2016 the 69th World Health Assembly adopted the global health sector strategy on viral hepatitis for the period 2016–2021,(2 as outlined in the report A69/32 of the Secretariat,(3 with the goal of eliminating viral hepatitis B and C by the year 2030. The global health sector strategy (GHSS on viral hepatitis has constructed a roadmap toward the elimination of viral hepatitis B and C, targeting five priority prevention and treatment interventions. Prevention involves universal hepatitis B immunization of infants, prevention of mother-to-child transmission, increased injection safety and blood safety, and increased harm reduction, the implementation of which will contribute toward universal health coverage, which is the target for Goal 3 of the 2030 Agenda for Sustainable Development. In combination with treatment of chronic hepatitis, the goal is to achieve by the year 2030 a reduction in the incidence of viral hepatitis by 90% and mortality by 65%.(3,4

  7. Viral RNA silencing suppression

    NARCIS (Netherlands)

    Hedil, Marcio; Kormelink, Richard

    2016-01-01

    The Bunyaviridae is a family of arboviruses including both plant-and vertebrate-infecting representatives. The Tospovirus genus accommodates plant-infecting bunyaviruses, which not only replicate in their plant host, but also in their insect thrips vector during persistent propagative

  8. Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring

    Science.gov (United States)

    Lovy, Jan; Lewis, N.L.; Hershberger, P.K.; Bennett, W.; Meyers, T.R.; Garver, K.A.

    2012-01-01

    Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring.

  9. Immigration and viral hepatitis

    OpenAIRE

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J.; Janssen, Harry

    2015-01-01

    textabstractWHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly or...

  10. 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

  11. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

    Directory of Open Access Journals (Sweden)

    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  12. Viral disorder or disordered viruses: do viral proteins possess unique features?

    Science.gov (United States)

    Xue, Bin; Williams, Robert W; Oldfield, Christopher J; Goh, Gerard Kian-Meng; Dunker, A K; Uversky, Vladimir N

    2010-08-01

    Many proteins or their regions are disordered in their native, biologically active states. Bioinformatics has revealed that these proteins/regions are highly abundant in different proteomes and carry out mostly regulatory functions related to molecular recognition, signal transduction, protein-protein, and protein-nucleic acid interactions. Viruses, these "organisms at the edge of life", have uniquely evolved to be highly adaptive for fast change in their biological and physical environment. To sustain these fast environmental changes, viral proteins elaborated multiple measures, from relatively low van der Waals contact densities, to inclusion of a large fraction of residues that are not arranged in well-defined secondary structural elements, to heavy use of short disordered regions, and to high resistance to mutations. On the other hand, viral proteins are rich in intrinsic disorder. Some of the intrinsically disordered regions are heavily used in the functioning of viral proteins. Others likely have evolved to help viruses accommodate to their hostile habitats. Still others evolved to help viruses in managing their economic usage of genetic material via alternative splicing, overlapping genes, and anti-sense transcription. In this review, we focus on structural peculiarities of viral proteins and on the role of intrinsic disorder in their functions.

  13. Persistent cellular metabolic changes after hemithyroidectomy for benign euthyroid goiter

    DEFF Research Database (Denmark)

    Toft Kristensen, Tina; Larsen, Jacob; Pedersen, Palle Lyngsie

    2014-01-01

    persistently increased TSH and decreased fT4, sustained mitochondrial hyperpolarization and increased V˙O2. Our results demonstrate a decrease after hemithyroidectomy of the metabolic state to which the individual is adapted, with persistent cellular metabolic changes in a hemithyroidectomized patient group...

  14. Stability of Bovine viral diarrhea virus 1 nucleic acid in fetal bovine samples stored under different conditions

    Science.gov (United States)

    Infection of pregnant cattle with bovine viral diarrhea viruses can result in reproductive disease that includes fetal reabsorption, mummification, abortion, still births, congenital defects affecting structural, neural, reproductive and immune systems and the birth of calves persistently infected w...

  15. Conditions for Viral Influence Spreading through Multiplex Correlated Social Networks

    Science.gov (United States)

    Hu, Yanqing; Havlin, Shlomo; Makse, Hernán A.

    2014-04-01

    A fundamental problem in network science is to predict how certain individuals are able to initiate new networks to spring up "new ideas." Frequently, these changes in trends are triggered by a few innovators who rapidly impose their ideas through "viral" influence spreading, producing cascades of followers and fragmenting an old network to create a new one. Typical examples include the rise of scientific ideas or abrupt changes in social media, like the rise of Facebook to the detriment of Myspace. How this process arises in practice has not been conclusively demonstrated. Here, we show that a condition for sustaining a viral spreading process is the existence of a multiplex-correlated graph with hidden "influence links." Analytical solutions predict percolation-phase transitions, either abrupt or continuous, where networks are disintegrated through viral cascades of followers, as in empirical data. Our modeling predicts the strict conditions to sustain a large viral spreading via a scaling form of the local correlation function between multilayers, which we also confirm empirically. Ultimately, the theory predicts the conditions for viral cascading in a large class of multiplex networks ranging from social to financial systems and markets.

  16. Kaposi’s Sarcoma Herpesvirus Genome Persistence

    Directory of Open Access Journals (Sweden)

    Franceline Juillard

    2016-08-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV has an etiologic role in Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. These diseases are most common in immunocompromised individuals, especially those with AIDS. Similar to all herpesviruses, KSHV infection is lifelong. KSHV infection in tumor cells is primarily latent, with only a small subset of cells undergoing lytic infection. During latency, the KSHV genome persists as a multiple copy, extrachromosomal episome in the nucleus. In order to persist in proliferating tumor cells, the viral genome replicates once per cell cycle and then segregates to daughter cell nuclei. KSHV only expresses several genes during latent infection. Prominent among these genes, is the latency-associated nuclear antigen (LANA. LANA is responsible for KSHV genome persistence and also exerts transcriptional regulatory effects. LANA mediates KSHV DNA replication and in addition, is responsible for segregation of replicated genomes to daughter nuclei. LANA serves as a molecular tether, bridging the viral genome to mitotic chromosomes to ensure that KSHV DNA reaches progeny nuclei. N-terminal LANA attaches to mitotic chromosomes by binding histones H2A/H2B at the surface of the nucleosome. C-terminal LANA binds specific KSHV DNA sequence and also has a role in chromosome attachment. In addition to the essential roles of N- and C-terminal LANA in genome persistence, internal LANA sequence is also critical for efficient episome maintenance. LANA’s role as an essential mediator of virus persistence makes it an attractive target for inhibition in order to prevent or treat KSHV infection and disease.

  17. Sustainable Food & Sustainable Economics

    OpenAIRE

    Alvarez, Mavis Dora

    2012-01-01

    Cuba today is immersed in a very intense process of perfecting its agricultural production structures with the goal of making them more efficient and sustainable in their economic administration and in their social and environmental management. Agricultural cooperatives in Cuba have the responsibility of producing on 73% of the country's farmland. Their contributions are decisive to developing agricultural production and to ensuring more and better food for the population, in addition to redu...

  18. Improved detection of Bovine Viral Diarrhea Virus in Bovine lymphoid cell lines using PrimeFlow RNA assay

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) infections, whether as acute, persistent or contributing to co-infections, result in significant losses for cattle producers. BVDV can be identified by real-time PCR and ELISA, detection and quantification of viral infection at the single cell level is extremely di...

  19. Norovirus Polymerase Fidelity Contributes to Viral Transmission In Vivo

    DEFF Research Database (Denmark)

    Arias Esteban, Armando; Thorne, Lucy; Ghurburrun, Elsa

    2016-01-01

    Intrahost genetic diversity and replication error rates are intricately linked to RNA virus pathogenesis, with alterations in viral polymerase fidelity typically leading to attenuation during infections in vivo. We have previously shown that norovirus intrahost genetic diversity also influences...... viral pathogenesis using the murine norovirus model, as increasing viral mutation frequency using a mutagenic nucleoside resulted in clearance of a persistent infection in mice. Given the role of replication fidelity and genetic diversity in pathogenesis, we have now investigated whether polymerase...... fidelity can also impact virus transmission between susceptible hosts. We have identified a high-fidelity norovirus RNA-dependent RNA polymerase mutant (I391L) which displays delayed replication kinetics in vivo but not in cell culture. The I391L polymerase mutant also exhibited lower transmission rates...

  20. Measles viral load may reflect SSPE disease progression

    Directory of Open Access Journals (Sweden)

    Jin L

    2006-06-01

    Full Text Available Abstract Subacute sclerosing panencephalitis (SSPE is a rare, slowly progressive neurological disorder caused by the persistent infection with measles virus (MV. Despite much research into SSPE, its pathology remains obscure. We examined autopsy tissues of eight SSPE patients by real time quantitative PCR, immunohistochemistry and immunoblotting to determine viral load. MV N, M and H gene RNA could be detected in the central nervous system (CNS of all patients and in two non-CNS tissues of one patient. The viral burden between patients differed up to four-fold by quantitative PCR and corresponded with detection of MV protein. The level of both viral RNA and antigen in the brain may correlate with disease progression.

  1. Equine viral arteritis

    Directory of Open Access Journals (Sweden)

    Kosec Marjan

    2016-01-01

    Full Text Available Equine viral arteritis (EVA is a contagious disease of equids caused by equine artheritis virus (EAV, widespread in most countries in the world, where patients are diagnosed. The infection usually starts asymptomatic. Clinical signs indicate respiratory infection of different intensity and also abortions are present at different stages of gestation. Large prevalence of this disease in the world has become a growing economic problem. The disease is specific to a particular kind of animals, and it affects only equids (horses, donkeys, mules, mule and zebras. In countries where the infection has been confirmed, the percentage of positive animals differ. Likewise, there is difference in percentage among certain animal kinds. The highest percentage of positive animals has been found in totters and the lowest in cold-blooded.

  2. Production and Titering of Recombinant Adeno-associated Viral Vectors

    OpenAIRE

    McClure, Christina; Cole, Katy L. H.; Wulff, Peer; Klugmann, Matthias; Murray, Andrew J.

    2011-01-01

    In recent years recombinant adeno-associated viral vectors (AAV) have become increasingly valuable for in vivo studies in animals, and are also currently being tested in human clinical trials. Wild-type AAV is a non-pathogenic member of the parvoviridae family and inherently replication-deficient. The broad transduction profile, low immune response as well as the strong and persistent transgene expression achieved with these vectors has made them a popular and versatile tool for in vitro and ...

  3. Viral gene therapy.

    Science.gov (United States)

    Mancheño-Corvo, P; Martín-Duque, P

    2006-12-01

    Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor. Many of these gene transfer vectors are modified viruses. The ability for the delivery of therapeutic genes, made them desirable for engineering virus vector systems. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Because these vector systems have unique advantages and limitations, each has applications for which it is best suited. Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction. Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination of infected cells often limits gene expression in vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression remain as obstacles. AAV also infects many non-dividing and dividing cell types, but has a limited DNA capacity. This review discusses current and emerging virusbased genetic engineering strategies for the delivery of therapeutic molecules or several approaches for cancer treatment.

  4. Mycoviruses, RNA silencing, and viral RNA recombination.

    Science.gov (United States)

    Nuss, Donald L

    2011-01-01

    In contrast to viruses of plants and animals, viruses of fungi, mycoviruses, uniformly lack an extracellular phase to their replication cycle. The persistent, intracellular nature of the mycovirus life cycle presents technical challenges to experimental design. However, these properties, coupled with the relative simplicity and evolutionary position of the fungal host, also provide opportunities for examining fundamental aspects of virus-host interactions from a perspective that is quite different from that pertaining for most plant and animal virus infections. This chapter presents support for this view by describing recent advances in the understanding of antiviral defense responses against one group of mycoviruses for which many of the technical experimental challenges have been overcome, the hypoviruses responsible for hypovirulence of the chestnut blight fungus Cryphonectria parasitica. The findings reveal new insights into the induction and suppression of RNA silencing as an antiviral defense response and an unexpected role for RNA silencing in viral RNA recombination. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. VIRAL DISEASES IN SEA FISH

    Directory of Open Access Journals (Sweden)

    Ivančica Strunjak-Perović

    1996-12-01

    Full Text Available Adequate knowledge on fish diseases caused by viruses is still lacking. Up until now, in fish which live their entire life cycle or part of it in the sea, some viral diseases have been determined (lymphoeytis, viral necrosis of crythrocytes, ciravosti cod syndrome, encephalitis, viral hemoragic septichemistry, viral hematopoetic necrosis, viral gusteraca necrosis, chum renviral infection, branchionephritis, rabdociral eel infection. Some of these diseases primarily occur in the freshwater phase of host development, although recordings exist that the virus is carried on in surving samples which succeed in making it to the sea. As the number of sea fish species increases in controlled culture a increasing number of pathological cases are observed, which is caused by viruses. Therefore, in this area it is necessary to emphasize future investigations.

  6. Murine liver-resident group 1 innate lymphoid cells regulate optimal priming of anti-viral CD8+ T cells.

    Science.gov (United States)

    Krueger, Peter D; Narayanan, Sowmya; Surette, Fionna A; Brown, Michael G; Sung, Sun-Sang J; Hahn, Young S

    2017-01-01

    The liver contains 2 transcriptionally distinct group 1 ILC subsets: CD49a+ ILC1s and CD49b+ NK cells. However, little is known about how group 1 ILCs contribute to hepatic immune responses. Therefore, we characterized murine liver-resident group 1 ILCs and found that CD49a+ ILC1s express high levels of the inhibitory receptor NKG2A and localize near DCs in perivascular spaces surrounding the portal triads. Upon hepatic viral infection, NKG2A signaling in group 1 ILCs, especially in CD49a+ ILC1s, inhibits CXCL9 expression required for robust accumulation of IFN-γ+CD49b+ NK cells. As a consequence, NKG2A-/- mice showed increased numbers of IFN-γ-producing NK cells that preferentially activate liver CD103+ DCs, leading to the sustained proliferation of adoptively transferred, virus-specific CD8+ T cells. Collectively, these data suggest that group 1 ILCs play a role in maintaining the liver as a tolerogenic site by limiting the recruitment of peripheral NK cells during the early phase of viral infection. Furthermore, our findings implicate that the inhibition of NKG2A signaling on group 1 ILCs may be a novel vaccine strategy to induce robust CD8+ T cell responses against persistent liver pathogens. © Society for Leukocyte Biology.

  7. Sustainability and sacred values

    Directory of Open Access Journals (Sweden)

    John Cairns Jr.

    2002-09-01

    Full Text Available Successful implementation of the quest for sustainable use of the planet requires that human society both reexamine and expand present views of what is sacred and what is not. The most important aspect will be going beyond a homocentric focus to a biocentric emphasis. A unifying theme would be the desire to leave a habitable planet for human descendants and those of other species. It is unlikely that society can be confident of achieving sustainability until persuasive evidence supporting this belief has existed for several generations. In order for sustainable use of the planet to persist indefinitely, the conditions essential to this state must be morally preserved on sacred grounds. Viewing natural systems as sacred requires not only preventing damage to them but, wherever possible, repairing damage to them caused by humankind.

  8. Demographics of antibiotic persistence

    DEFF Research Database (Denmark)

    Kollerova, Silvia; Jouvet, Lionel; Steiner, Ulrich

    Persister cells, cells that can survive antibiotic exposure but lack heritable antibiotic resistance, are assumed to play a crucial role for the evolution of antibiotic resistance. Persistence is a stage associated with reduced metabolic activity. Most previous studies have been done on batch...... even play a more prominent role for the evolution of resistance and failures of medical treatment by antibiotics as currently assumed....

  9. Persistent hepatitis virus infection and immune homeostasis

    Directory of Open Access Journals (Sweden)

    ZHOU Yun

    2014-09-01

    Full Text Available Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the process involving various immune cells and molecules and is the result of homeostasis maintenance in antiviral immune response. The immune homeostasis maintained during persistent infections with hepatitis viruses is analyzed by the cellular and molecular mechanisms.

  10. Viral asthma: implications for clinical practice

    Directory of Open Access Journals (Sweden)

    Roger Menendez

    2010-07-01

    Full Text Available Roger Menendez1, Michael D Goldman21Allergy and Asthma Center of El Paso, El Paso, TX, USA; 2Pulmonary Division, UCLA Gaffen School of Medicine, Los Angeles, CA, USAAbstract: The natural history of asthma appears to be driven primarily by the timing and duration of viral respiratory infections. From the very high rate of infections in childhood, to the more sporadic pattern seen in adults, the cycle of acute injury followed by an inefficient repair process helps explain the clinical patterns of asthma severity currently recognized by asthma guidelines. Why the asthmatic host responds to viral injury in a particular way is largely a mystery and the subject of intense investigation. The role of viruses in asthma extends not just to intermittent but to persistent disease, and to both the atopic as well as nonatopic phenotypes. Future therapeutic strategies should include primary prevention via the development of antiviral innate immunity-enhancing vaccines, as well as secondary prevention via the use of antiviral agents, or immunomodulators designed to boost the antiviral response or interrupt the proinflammatory cascade.Keywords: asthma, rhinoviruses, exacerbations, epidemiology, phenotypes, clinical trials

  11. Genome trimming by Borna disease viruses: viral replication control or escape from cellular surveillance?

    Science.gov (United States)

    Schneider, U; Martin, A; Schwemmle, M; Staeheli, P

    2007-05-01

    Persistence of RNA viruses is frequently associated with non-uniform terminal nucleotide deletions at both ends of the viral genome, which are believed to restrict viral replication and transcription during persistent infection. Borna disease virus (BDV), a negative strand RNA virus with no recognizable acute phase, quickly establishes persistence. We recently demonstrated that the vast majority of BDV genomes and antigenomes possess uniformly trimmed 5' termini, even if the virus is recovered from complementary DNA encoding a hypothetical full-length viral genome. Here we discuss different mechanisms which might lead to the selective 5'-terminal trimming of the BDV genome and subsequent retrieval of the lost genetic information. We further discuss possible benefits of genome trimming in the light of recent findings that terminal RNA structures are recognized by intracellular sensors which trigger innate immunity. We hypothesize that 5'-terminal genome trimming might represent a smart strategy of BDV to evade the antiviral host response.

  12. Insulated Foamy Viral Vectors

    Science.gov (United States)

    Browning, Diana L.; Collins, Casey P.; Hocum, Jonah D.; Leap, David J.; Rae, Dustin T.; Trobridge, Grant D.

    2016-01-01

    Retroviral vector-mediated gene therapy is promising, but genotoxicity has limited its use in the clinic. Genotoxicity is highly dependent on the retroviral vector used, and foamy viral (FV) vectors appear relatively safe. However, internal promoters may still potentially activate nearby genes. We developed insulated FV vectors, using four previously described insulators: a version of the well-studied chicken hypersensitivity site 4 insulator (650cHS4), two synthetic CCCTC-binding factor (CTCF)-based insulators, and an insulator based on the CCAAT box-binding transcription factor/nuclear factor I (7xCTF/NF1). We directly compared these insulators for enhancer-blocking activity, effect on FV vector titer, and fidelity of transfer to both proviral long terminal repeats. The synthetic CTCF-based insulators had the strongest insulating activity, but reduced titers significantly. The 7xCTF/NF1 insulator did not reduce titers but had weak insulating activity. The 650cHS4-insulated FV vector was identified as the overall most promising vector. Uninsulated and 650cHS4-insulated FV vectors were both significantly less genotoxic than gammaretroviral vectors. Integration sites were evaluated in cord blood CD34+ cells and the 650cHS4-insulated FV vector had fewer hotspots compared with an uninsulated FV vector. These data suggest that insulated FV vectors are promising for hematopoietic stem cell gene therapy. PMID:26715244

  13. Tight Junctions Go Viral!

    Directory of Open Access Journals (Sweden)

    Jesús M. Torres-Flores

    2015-09-01

    Full Text Available Tight junctions (TJs are highly specialized membrane domains involved in many important cellular processes such as the regulation of the passage of ions and macromolecules across the paracellular space and the establishment of cell polarity in epithelial cells. Over the past few years there has been increasing evidence that different components of the TJs can be hijacked by viruses in order to complete their infectious cycle. Viruses from at least nine different families of DNA and RNA viruses have been reported to use TJ proteins in their benefit. For example, TJ proteins such as JAM-A or some members of the claudin family of proteins are used by members of the Reoviridae family and hepatitis C virus as receptors or co-receptors during their entry into their host cells. Reovirus, in addition, takes advantage of the TJ protein Junction Adhesion Molecule-A (JAM-A to achieve its hematogenous dissemination. Some other viruses are capable of regulating the expression or the localization of TJ proteins to induce cell transformation or to improve the efficiency of their exit process. This review encompasses the importance of TJs for viral entry, replication, dissemination, and egress, and makes a clear statement of the importance of studying these proteins to gain a better understanding of the replication strategies used by viruses that infect epithelial and/or endothelial cells.

  14. 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 ...

  15. Viral infections as controlling factors for the deep biosphere? (Invited)

    Science.gov (United States)

    Engelen, B.; Engelhardt, T.; Sahlberg, M.; Cypionka, H.

    2009-12-01

    biogeography? Can viral infections tell us something about the physiological state of indigenous microorganisms? Finally, we will obtain estimates for the viral shunt as an important factor for sustaining the deep biosphere. References: Batzke A, Engelen B, Sass H, Cypionka H (2007) Phylogenetic and physiological diversity of cultured deep-biosphere bacteria from Equatorial Pacific Ocean and Peru Margin sediments. Geomicrobiology J 24:261-273 Danovaro R, Dell'Anno A, Corinaldesi C, Magagnini M, Noble R, Tamburini C, Weinbauer M (2008) Major viral impact on the functioning of benthic deep-sea ecosystems. Nature 454: 1084-U1027.

  16. Persistence and expression of Microplitis demolitor polydnavirus in Pseudoplusia includens.

    Science.gov (United States)

    Strand, M R; McKenzie, D I; Grassl, V; Dover, B A; Aiken, J M

    1992-07-01

    Persistence and expression of Microplitis demolitor polydnavirus (MdPDV) was examined in parasitized and virus-injected Pseudoplusia includens larvae. Viral DNA persisted in P. includens larvae for 6 days, but no increase in the amount of viral DNA present was detected. Viral transcripts were observed in parasitized and virus-injected larvae 4 h post-parasitism and expression continued for 6 days. When specific host tissues were examined, more viral DNA and RNA was detected in haemocytes than in the gut, nervous system and fat body. 32P-labelled MdPDV DNA hybridized to approximately six different size classes of mRNAs on Northern blots of RNA from haemocytes of parasitized larvae. MdPDV transcription was first detected in haemocytes at 4 h post-parasitism and continued for 6 days. Similar transcripts were observed in haemocytes from larvae that had been injected with calyx fluid or MdPDV plus venom. First-strand cDNA probes of haemocyte-specific MdPDV transcripts hybridized to only certain MdPDV viral DNAs, suggesting that only part of the MdPDV genome is expressed in this host cell type.

  17. Diel cycling and long-term persistence of viruses in the ocean’s euphotic zone

    Science.gov (United States)

    Aylward, Frank O.; Boeuf, Dominique; Mende, Daniel R.; Wood-Charlson, Elisha M.; Vislova, Alice; Eppley, John M.; Romano, Anna E.

    2017-01-01

    Viruses are fundamental components of marine microbial communities that significantly influence oceanic productivity, biogeochemistry, and ecosystem processes. Despite their importance, the temporal activities and dynamics of viral assemblages in natural settings remain largely unexplored. Here we report the transcriptional activities and variability of dominant dsDNA viruses in the open ocean’s euphotic zone over daily and seasonal timescales. While dsDNA viruses exhibited some fluctuation in abundance in both cellular and viral size fractions, the viral assemblage was remarkably stable, with the most abundant viral types persisting over many days. More extended time series indicated that long-term persistence (>1 y) was the rule for most dsDNA viruses observed, suggesting that both core viral genomes as well as viral community structure were conserved over interannual periods. Viral gene transcription in host cell assemblages revealed diel cycling among many different viral types. Most notably, an afternoon peak in cyanophage transcriptional activity coincided with a peak in Prochlorococcus DNA replication, indicating coordinated diurnal coupling of virus and host reproduction. In aggregate, our analyses suggested a tightly synchronized diel coupling of viral and cellular replication cycles in both photoautotrophic and heterotrophic bacterial hosts. A surprising consequence of these findings is that diel cycles in the ocean’s photic zone appear to be universal organizing principles that shape ecosystem dynamics, ecological interactions, and biogeochemical cycling of both cellular and acellular community components. PMID:29073070

  18. Diel cycling and long-term persistence of viruses in the ocean's euphotic zone.

    Science.gov (United States)

    Aylward, Frank O; Boeuf, Dominique; Mende, Daniel R; Wood-Charlson, Elisha M; Vislova, Alice; Eppley, John M; Romano, Anna E; DeLong, Edward F

    2017-10-24

    Viruses are fundamental components of marine microbial communities that significantly influence oceanic productivity, biogeochemistry, and ecosystem processes. Despite their importance, the temporal activities and dynamics of viral assemblages in natural settings remain largely unexplored. Here we report the transcriptional activities and variability of dominant dsDNA viruses in the open ocean's euphotic zone over daily and seasonal timescales. While dsDNA viruses exhibited some fluctuation in abundance in both cellular and viral size fractions, the viral assemblage was remarkably stable, with the most abundant viral types persisting over many days. More extended time series indicated that long-term persistence (>1 y) was the rule for most dsDNA viruses observed, suggesting that both core viral genomes as well as viral community structure were conserved over interannual periods. Viral gene transcription in host cell assemblages revealed diel cycling among many different viral types. Most notably, an afternoon peak in cyanophage transcriptional activity coincided with a peak in Prochlorococcus DNA replication, indicating coordinated diurnal coupling of virus and host reproduction. In aggregate, our analyses suggested a tightly synchronized diel coupling of viral and cellular replication cycles in both photoautotrophic and heterotrophic bacterial hosts. A surprising consequence of these findings is that diel cycles in the ocean's photic zone appear to be universal organizing principles that shape ecosystem dynamics, ecological interactions, and biogeochemical cycling of both cellular and acellular community components. Copyright © 2017 the Author(s). Published by PNAS.

  19. Sustainable agriculture

    National Research Council Canada - National Science Library

    Lichtfouse, Eric

    2009-01-01

    ... : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 9 Part I CLIMATE CHANGE Soils and Sustainable Agriculture: A Review : : : : : : : : : : : : : : : : : : : : : : : : : : Rattan Lal 15 Soils and Food Sufficiency...

  20. 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.

  1. Sustainable Marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    In this article, three different conceptions of sustainable marketing are discussed and compared. These different conceptions are referred to as social, green, and critical sustainable marketing. Social sustainable marketing follows the logic of demand-driven marketing management and places the

  2. Conditions for Viral Influence Spreading through Multiplex Correlated Social Networks

    Directory of Open Access Journals (Sweden)

    Yanqing Hu

    2014-05-01

    Full Text Available A fundamental problem in network science is to predict how certain individuals are able to initiate new networks to spring up “new ideas.” Frequently, these changes in trends are triggered by a few innovators who rapidly impose their ideas through “viral” influence spreading, producing cascades of followers and fragmenting an old network to create a new one. Typical examples include the rise of scientific ideas or abrupt changes in social media, like the rise of Facebook to the detriment of Myspace. How this process arises in practice has not been conclusively demonstrated. Here, we show that a condition for sustaining a viral spreading process is the existence of a multiplex-correlated graph with hidden “influence links.” Analytical solutions predict percolation-phase transitions, either abrupt or continuous, where networks are disintegrated through viral cascades of followers, as in empirical data. Our modeling predicts the strict conditions to sustain a large viral spreading via a scaling form of the local correlation function between multilayers, which we also confirm empirically. Ultimately, the theory predicts the conditions for viral cascading in a large class of multiplex networks ranging from social to financial systems and markets.

  3. Neuroanatomy goes viral!

    Directory of Open Access Journals (Sweden)

    Jonathan eNassi

    2015-07-01

    Full Text Available The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist's toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic

  4. Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection

    Science.gov (United States)

    Cheng, Liang; Yu, Haisheng; Li, Guangming; Li, Feng; Ma, Jianping; Li, Jingyun; Chi, Liqun; Zhang, Liguo

    2017-01-01

    The direct link between sustained type I interferon (IFN-I) signaling and HIV-1–induced immunopathogenesis during chronic infection remains unclear. Here we report studies using a monoclonal antibody to block IFN-α/β receptor 1 (IFNAR1) signaling during persistent HIV-1 infection in humanized mice (hu-mice). We discovered that, during chronic HIV-1 infection, IFNAR blockade increased viral replication, which was correlated with elevated T cell activation. Thus, IFN-Is suppress HIV-1 replication during the chronic phase but are not essential for HIV-1–induced aberrant immune activation. Surprisingly, IFNAR blockade rescued both total human T cell and HIV-specific T cell numbers despite elevated HIV-1 replication and immune activation. We showed that IFNAR blockade reduced HIV-1–induced apoptosis of CD4+ T cells. Importantly, IFNAR blockade also rescued the function of human T cells, including HIV-1–specific CD8+ and CD4+ T cells. We conclude that during persistent HIV-1 infection, IFN-Is suppress HIV-1 replication, but contribute to depletion and dysfunction of T cells. PMID:28614789

  5. Viral marketing as epidemiological model

    CERN Document Server

    Rodrigues, Helena Sofia

    2015-01-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of the critical factors to this communications strategy effectiveness remain largely unknown, the mathematical models in epidemiology are presented in this marketing specific field. In this paper, an epidemiological model SIR (Susceptible- Infected-Recovered) to study the effects of a viral marketing strategy is presented. It is made a comparison between the disease parameters and the marketing application, and simulations using the Matlab software are performed. Finally, some conclusions are given and their marketing impli...

  6. FastStats: Viral Hepatitis

    Science.gov (United States)

    ... Submit What's this? Submit Button NCHS Home Viral Hepatitis Recommend on Facebook Tweet Share Compartir Data are for the U.S. Morbidity Number of new hepatitis A cases: 1,239 (2014) Number of new ...

  7. Aseptic meningitis and viral myelitis.

    Science.gov (United States)

    Irani, David N

    2008-08-01

    Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system, respectively. The number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal central nervous system infections, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with noninfectious disorders that cause acute flaccid paralysis. This article reviews some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus is placed on the diseases caused by enteroviruses, which as a group account for most aseptic meningitis cases and many focal infections of the spinal cord.

  8. Viral Evolution Core | FNLCR Staging

    Science.gov (United States)

    Brandon F. Keele, Ph.D. PI/Senior Principal Investigator, Retroviral Evolution Section Head, Viral Evolution Core Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research Frederick, MD 21702-1201 Tel: 301-846-173

  9. Viral hepatitis in minority America.

    Science.gov (United States)

    Rawls, Renard A; Vega, Kenneth J

    2005-02-01

    Viral hepatitis continues as an important public health concern in the United States. Available data indicate that acute and chronic viral hepatitis remains an important cause of morbidity and mortality in this country despite the availability of immunization for hepatitis A and B and pharmacologic therapy for chronic hepatitis B and C. Minority populations within the United States are disproportionately affected by acute and chronic viral hepatitis. Many diseases, for example, Barrett's esophagus, affect ethnic groups differently. Viral hepatitis A, B, and C may demonstrate ethnic variation with regard to their epidemiology, natural history, clinicopatholgic findings, complications, and treatment outcomes. This report will review the literature regarding these areas in hepatitis A, B, and C among the African American, Hispanic American, and Native American populations of the United States.

  10. Is Inflation Persistence Over?

    Directory of Open Access Journals (Sweden)

    Fernando N. de Oliveira

    2014-09-01

    Full Text Available We analyze inflation persistence in several industrial and emerging countries in the recent past by implementing unit root tests in the presence of unknown structural breaks and by estimating reduced-form models of inflation dynamics. We select a very representative group of 23 industrial and 17 emerging economies. Our sample period is comprised of quarterly data and differs for each country. Our results indicate that inflation persistence is decreasing over time for the great majority of industrial economies. Many emerging economies, however, show increasing persistence and even a few have highly persistent inflationary processes. We also observe structural breaks in all inflation processes we study with the exception of the inflation processes of Germany and Austria. Our results are robust to different reduced forms of the inflation processes and different econometric techniques.

  11. Persistent facial pain conditions

    DEFF Research Database (Denmark)

    Forssell, Heli; Alstergren, Per; Bakke, Merete

    2016-01-01

    TMD, and different neuropathic or putative neuropathic facial pains such as persistent idiopathic facial pain and atypical odontalgia, trigeminal neuralgia and painful posttraumatic trigeminal neuropathy. The article presents an overview of TMD pain as a biopsychosocial condition, its prevalence...

  12. Microbiological diagnostics of viral hepatitis

    OpenAIRE

    HASDEMİR, Ufuk

    2016-01-01

    Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

  13. Coinhibitory Receptor Expression and Immune Checkpoint Blockade: Maintaining a Balance in CD8+ T Cell Responses to Chronic Viral Infections and Cancer

    Directory of Open Access Journals (Sweden)

    Isobel S. Okoye

    2017-09-01

    Full Text Available In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called “immune checkpoints” by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer. With the paucity of therapeutic vaccines against chronic infections such as HIV, HPV, hepatitis B, and hepatitis C, such adjunct checkpoint blockade strategies are required including the blockade of other inhibitory receptors such as T cell immunoreceptor with immunoglobulin (Ig and immunoreceptor tyrosine-based inhibitory motif domains, T cell Ig and mucin-domain containing-3, lymphocyte activation gene 3, and V-domain Ig-containing suppressor of T cell activation. The nature of different chronic viral infections and cancers is likely to influence the level, composition, and pattern of inhibitory receptors expressed by responding T cells. This will have implications for checkpoint antibody blockade strategies employed for treating tumors and chronic viral infections. Here, we review recent advances that provide a clearer insight into the role of coinhibitory receptor expression in T cell exhaustion and reveal novel antibody-blockade therapeutic targets for chronic viral infections and cancer. Understanding the mechanism of T cell exhaustion in response to chronic virus infections and cancer as well as the nature of restored T cell responses will contribute to further improvement of immune checkpoint blockade strategies.

  14. Recovery, persistence, and sequelae in hepatitis C virus infection: a perspective on long-term outcome.

    Science.gov (United States)

    Alter, H J; Seeff, L B

    2000-01-01

    Hepatitis C has emerged in recent years as the most common basis for liver disease in the United States, having infected an estimated 3.9 million people in this country and an estimated 170 million worldwide. Currently, it is the predominant reason for undergoing liver transplantation. The disease it causes is characterized by silent onset in most infected individuals, a high rate of viral persistence, and the potential for development of ever-worsening chronic liver disease, ranging from chronic hepatitis to cirrhosis and occasionally to hepatocellular carcinoma. Such progression, when it occurs, is also most commonly a silent process that may take 20-40, and occasionally even more, years to reach its end point. Because of these characteristics, it has been exceedingly difficult to accurately assess the natural history. Efforts to accomplish this have consisted of retrospective, prospective, and cohort studies. The most concerning data have derived from the retrospective study approach, generally performed at tertiary referral centers. Because these centers commonly attract persons with existing chronic liver disease, they have tended to describe a high rate of progression to cirrhosis and cancer. This "referral bias" is avoided in the prospective and cohort study approach, and data derived from these studies indicate a lower rate of progression and a correspondingly higher rate of either recovery or minimal liver disease. In this review, we briefly describe potential mechanisms of viral persistence; present detailed information on outcomes that have derived from retrospective, prospective, and cohort studies, involving both adults and children; examine the data regarding progression of fibrosis and of progression to hepatocellular carcinoma; consider cofactors that might enhance liver disease progression; and report the emerging data that suggest that spontaneous viral clearance may be higher than is currently believed. We conclude with the view that severe, life

  15. Sustainable Disruptions

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes...

  16. Infection Programs Sustained Lymphoid Stromal Cell Responses and Shapes Lymph Node Remodeling upon Secondary Challenge

    Directory of Open Access Journals (Sweden)

    Julia L. Gregory

    2017-01-01

    Full Text Available Lymph nodes (LNs are constructed of intricate networks of endothelial and mesenchymal stromal cells. How these lymphoid stromal cells (LSCs regulate lymphoid tissue remodeling and contribute to immune responses remains poorly understood. We performed a comprehensive functional and transcriptional analysis of LSC responses to skin viral infection and found that LSC subsets responded robustly, with different kinetics for distinct pathogens. Recruitment of cells to inflamed LNs induced LSC expansion, while B cells sustained stromal responses in an antigen-independent manner. Infection induced rapid transcriptional responses in LSCs. This transcriptional program was transient, returning to homeostasis within 1 month of infection, yet expanded fibroblastic reticular cell networks persisted for more than 3 months after infection, and this altered LN composition reduced the magnitude of LSC responses to subsequent heterologous infection. Our results reveal the complexity of LSC responses during infection and suggest that amplified networks of LN stromal cells support successive immune responses.

  17. [Neuropsychiatric sequelae of viral meningitis in adults].

    Science.gov (United States)

    Damsgaard, Jesper; Hjerrild, Simon; Renvillard, Signe Groth; Leutscher, Peter Derek Christian

    2011-10-10

    Viral meningitis is considered to be a benign illness with only mild symptoms. In contrast to viral encephalitis and bacterial meningitis, the prognosis is usually good. However, retrospective studies have demonstrated that patients suffering from viral meningitis may experience cognitive impairment following the acute course of infection. Larger controlled studies are needed to elucidate the potential neuropsychiatric adverse outcome of viral meningitis.

  18. Computational sustainability

    CERN Document Server

    Kersting, Kristian; Morik, Katharina

    2016-01-01

    The book at hand gives an overview of the state of the art research in Computational Sustainability as well as case studies of different application scenarios. This covers topics such as renewable energy supply, energy storage and e-mobility, efficiency in data centers and networks, sustainable food and water supply, sustainable health, industrial production and quality, etc. The book describes computational methods and possible application scenarios.

  19. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

  20. Clonal Expansion of Human Immunodeficiency Virus-Infected Cells and Human Immunodeficiency Virus Persistence During Antiretroviral Therapy.

    Science.gov (United States)

    Mullins, James I; Frenkel, Lisa M

    2017-03-15

    The latent HIV-1 reservoir in blood decays very slowly, even during prolonged suppression of viral replication by antiretroviral therapy (ART). Mechanisms for reservoir persistence include replenishment through low-level viral replication, longevity and homeostatic proliferation of memory T cells, and most recently appreciated, clonal expansion of HIV-infected cells. Clonally expanded cells make up a large and increasing fraction of the residual infected cell population on ART, and insertion of HIV proviruses into certain host cellular genes has been associated with this proliferation. That the vast majority of proviruses are defective clouds our assessment of the degree to which clonally expanded cells harbor infectious viruses, and thus the extent to which they contribute to reservoirs relevant to curing infection. This review summarizes past studies that have defined our current understanding and the gaps in our knowledge of the mechanisms by which proviral integration and clonal expansion sustain the HIV reservoir. © 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.

  1. [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.

  2. Persistent arm pain is distinct from persistent breast pain following breast cancer surgery.

    Science.gov (United States)

    Langford, Dale J; Paul, Steven M; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D; Hamolsky, Deborah; Luce, Judith A; Kober, Kord M; Neuhaus, John M; Cooper, Bruce A; Aouizerat, Bradley E; Miaskowski, Christine

    2014-12-01

    Persistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N = 398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. To persist or not to persist?

    Science.gov (United States)

    Hofbauer, Josef; Schreiber, Sebastian J.

    2004-07-01

    Ecological vector fields \\dot x_i = x_if_i(x) on the non-negative cone \\\\bf R^n_+ on Rn are often used to describe the dynamics of n interacting species. These vector fields are called permanent (or uniformly persistent) if the boundary \\partial {\\bf R}^n_+ of the non-negative cone is repelling. We construct an open set of ecological vector fields containing a dense subset of permanent vector fields and containing a dense subset of vector fields with attractors on \\partial {\\bf R}^n_+ . In particular, this construction implies that robustly permanent vector fields are not dense in the space of permanent vector fields. Hence, verifying robust permanence is important. We illustrate this result with ecological vector fields involving five species that admit a heteroclinic cycle between two equilibria and the Hastings-Powell teacup attractor.

  4. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

    2016-01-01

    Viral envelope glycoproteins are major targets for antibodies that bind to and inactivate viral particles. The capacity of a viral vaccine to induce virus-neutralizing antibodies is often used as a marker for vaccine efficacy. Yet the number of known neutralization target epitopes is restricted...... variations at glycosylation sites. In conclusion, the viral O-glycosyl peptide epitopes may be of relevance for development of subunit vaccines and for improved serodiagnosis of viral diseases. Copyright © 2015 John Wiley & Sons, Ltd....

  5. Defining persistent hotspots

    DEFF Research Database (Denmark)

    Kittur, Nupur; Binder, Sue; Campbell, Carl H.

    2017-01-01

    , investigators and neglected tropical disease (NTD) program managers need to define them based on changes in prevalence and/or intensity. But how should the data be analyzed to define a persistent hotspot? We have analyzed a dataset from an operational research study in western Tanzania after three annual MDAs...... and contrast the outcomes of these analyses. Our intent is to showhowthe samedataset yields different numbers of persistent hotspots depending on the approach used to define them. We suggest that investigators and NTD program managers use the approach most suited for their study or program, but whichever...... using four different approaches to define persistent hotspots. The four approaches are 1) absolute percent change in prevalence; 2) percent change in prevalence; 3) change in World Health Organization guideline categories; 4) change (absolute or percent) in both prevalence and intensity. We compare...

  6. Persistent luminescence nanothermometers

    Science.gov (United States)

    Martín Rodríguez, Emma; López-Peña, Gabriel; Montes, Eduardo; Lifante, Ginés; García Solé, José; Jaque, Daniel; Diaz-Torres, Luis Armando; Salas, Pedro

    2017-08-01

    Persistent phosphorescence nanoparticles emitting in the red and near-infrared spectral regions are strongly demanded as contrast nanoprobes for autofluorescence free bioimaging and biosensing. In this work, we have developed Sr4Al14O25:Eu2+, Cr3+, Nd3+ nanopowders that produce persistent red phosphorescence peaking at 694 nm generated by Cr3+ ions. This emission displays temperature sensitivity in the physiological temperature range (20-60 °C), which makes these nanoparticles potentially useful as fluorescence (contactless) nanothermometers operating without requiring optical excitation. Nd3+ ions, which act as shallow electron traps for the red Cr3+ persistent emission, also display infrared emission bands, extending the fluorescence imaging capability to the second biological window. This unique combination of properties makes these nanoparticles multifunctional luminescent probes with great potential applications in nanomedicine.

  7. Why do delusions persist?

    Directory of Open Access Journals (Sweden)

    Philip R Corlett

    2009-07-01

    Full Text Available Delusions are bizarre and distressing beliefs that characterize certain mental illnesses. They arise without clear reasons and are remarkably persistent. Recent models of delusions, drawing on a neuroscientific understanding of learning, focus on how delusions might emerge from abnormal experience. We believe that these models can be extended to help us understand why delusions persist. We consider prediction error, the mismatch between expectancy and experience, to be central. Surprising events demand a change in our expectancies. This involves making what we have learned labile, updating and binding the memory anew: a process of memory reconsolidation. We argue that, under the influence of excessive prediction error, delusional beliefs are repeatedly reconsolidated, strengthening them so that they persist, apparently impervious to contradiction.

  8. Case report of rabies-induced persistent mental symptoms

    OpenAIRE

    Wang, Xiaoqing; Yu, Xiaowen; Guan, Yangtai

    2015-01-01

    Summary Rabies is a viral infection with a high case fatality rate. Typical symptoms of rabies include hydrophobia, pharynx muscle spasms, and progressive paralysis. Rabies-induced persistent mental disturbances are rare. Here we report a 22-year-old male who was infected with rabies after being attacked by a dog. He did not receive rabies vaccine immediately after the incident and was only provided with non-standard treatment at a local clinic. A week later he became disorientated, paranoid,...

  9. Sustainable Transportation

    DEFF Research Database (Denmark)

    Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

    2014-01-01

    that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...

  10. Sustaining dairy

    NARCIS (Netherlands)

    Villarreal Herrera, Georgina

    2017-01-01

    Dairy in Europe has undergone many changes in the last few years—the abolition of milk production quotas being a fundamental one. This study explores these changes in relation to the sustained social and environmental viability of the sector and how dairy processors' sustainability

  11. Sustainable Universities

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2011-01-01

    . Declarations tend to have impact on three trends. Firstly, there is emerging international consensus on the university’s role and function in relation to sustainable development; secondly, the emergence of national legislation, and thirdly, an emerging international competition to be leader in sustainable...... campus performance....

  12. Sustainable Transition

    DEFF Research Database (Denmark)

    Hansen, Ole Erik; Søndergård, Bent

    2014-01-01

    of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...

  13. Sustainable Learning

    Science.gov (United States)

    Cadwell, Louise; Dillon, Robert

    2011-01-01

    Green schools have moved into a new era that focuses on building a culture of sustainability in every aspect of learning in schools. In the early stages of sustainability education, the focus was on recycling and turning off the lights. Now, students and adults together are moving into the areas of advocacy and action that are based on a deep…

  14. 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.

  15. Acute bacterial and viral meningitis.

    Science.gov (United States)

    Bartt, Russell

    2012-12-01

    Most cases of acute meningitis are infectious and result from a potentially wide range of bacterial and viral pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Acute meningitis is infectious in most cases and caused by a potentially wide range of bacterial and viral pathogens. Shifts in the epidemiology of bacterial pathogens have been influenced by changes in vaccines and their implementation. Seasonal and environmental changes influence the likely viral and rickettsial pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Pertinent testing and treatment can vary with the clinical presentation, season, and possible exposures. This article reviews the epidemiology, clinical presentation, diagnosis, and treatment of acute meningitis.

  16. Beyond viral suppression of HIV

    DEFF Research Database (Denmark)

    Lazarus, Jeffrey V.; Safreed-Harmon, Kelly; Barton, Simon E

    2016-01-01

    BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed......, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target...... for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV...

  17. Experimental infection of reindeer with bovine viral diarrhea virus

    Directory of Open Access Journals (Sweden)

    J.K. Morton

    1990-08-01

    Full Text Available Two 8-month reindeer (Rangifer tarandus and a 1-month-old Hereford-Holstein calf (Bos taurus were inoculated intranasally with the Singer (cytopathogenic strain of bovine viral diarrhea (BVD virus. Clinical signs in reindeer included loose stools containing blood and mucus, and transient laminitis or coronitis. Signs in the calf were limited to bloody mucus in the stool and lesions in the nasal mucosa. Antibody titers to BVD virus in the reindeer were intermittent, and titers in the calf persisted from days 14 to 63 post-inoculation (PI. Viremia was detected on PI day 4 in one reindeer, days 3-7 in the other, and days 2-7 in the calf. Bovine viral diarrhea virus was isolated from the lung of the calf at necropsy (PI day 63.

  18. Equine viral arteritis in breeding and sport horses in central Spain

    NARCIS (Netherlands)

    Cruz-Lopez, Fatima; Newton, Richard; Sanchez-Rodriguez, Ana; Ireland, Joanne; Mughini-Gras, Lapo|info:eu-repo/dai/nl/413306046; Moreno, Miguel A; Fores, Paloma

    2017-01-01

    Equine viral arteritis (EVA) may have a high economic impact on breeding stud farms due to the occurrence of EVA-associated abortion outbreaks and the ability of the virus to persist in carrier stallions. While the consequences of EVA in premises with sport horses are usually less severe, the first

  19. Persistent facial pain conditions

    DEFF Research Database (Denmark)

    Forssell, Heli; Alstergren, Per; Bakke, Merete

    2016-01-01

    Persistent facial pains, especially temporomandibular disorders (TMD), are common conditions. As dentists are responsible for the treatment of most of these disorders, up-to date knowledge on the latest advances in the field is essential for successful diagnosis and management. The review covers...

  20. Persistent organic pollutants

    NARCIS (Netherlands)

    Dungen, van den M.W.

    2016-01-01

    Wild caught fish, especially marine fish, can contain high levels of persistent organic pollutants (POPs). In the Netherlands, especially eel from the main rivers have high POP levels. This led to a ban in 2011 on eel fishing due to health concerns. Many of the marine POPs have been related to

  1. Is corruption really persistent?

    NARCIS (Netherlands)

    Seldadyo, H.; de Haan, J.

    Theoretical and empirical research on corruption generally concludes that corruption is persistent. However, using International Country Risk Guide data for the period 1984-2008 for 101 countries, we find strong evidence that corruption changes over time. In the present study, corruption levels of

  2. Contributions to Persistence Theory

    Directory of Open Access Journals (Sweden)

    Du Dong

    2014-12-01

    Full Text Available Persistence theory discussed in this paper is an application of algebraic topology (Morse Theory [29] to Data Analysis, precisely to qualitative understanding of point cloud data, or PCD for short. PCD can be geometrized as a filtration of simplicial complexes (Vietoris-Rips complex [25] [36] and the homology changes of these complexes provide qualitative information about the data. Bar codes describe the changes in homology with coefficients in a fixed field. When the coefficient field is ℤ2, the calculation of bar codes is done by ELZ algorithm (named after H. Edelsbrunner, D. Letscher, and A. Zomorodian [20]. When the coefficient field is ℝ, we propose an algorithm based on the Hodge decomposition [17]. With Dan Burghelea and Tamal K. Dey we developed a persistence theory which involves level sets discussed in Section 4. We introduce and discuss new computable invariants, the “relevant level persistence numbers” and the “positive and negative bar codes”, and explain how they are related to the bar codes for level persistence. We provide enhancements and modifications of ELZ algorithm to calculate such invariants and illustrate them by examples.

  3. Filamentous Structures Induced by a Phytoreovirus Mediate Viral Release from Salivary Glands in Its Insect Vector.

    Science.gov (United States)

    Mao, Qianzhuo; Liao, Zhenfeng; Li, Jiajia; Liu, Yuyan; Wu, Wei; Chen, Hongyan; Chen, Qian; Jia, Dongsheng; Wei, Taiyun

    2017-06-15

    Numerous viral pathogens are persistently transmitted by insect vectors and cause agricultural or health problems. These viruses circulate in the vector body, enter the salivary gland, and then are released into the apical plasmalemma-lined cavities, where saliva is stored. The cavity plasmalemma of vector salivary glands thus represents the last membrane barrier for viral transmission. Here, we report a novel mechanism used by a persistent virus to overcome this essential barrier. We observed that the infection by rice gall dwarf virus (RGDV), a species of the genus Phytoreovirus in the family Reoviridae, induced the formation of virus-associated filaments constructed by viral nonstructural protein Pns11 within the salivary glands of its leafhopper vector, Recilia dorsalis Such filaments attached to actin-based apical plasmalemma and induced an exocytosis-like process for viral release into vector salivary gland cavities, through a direct interaction of Pns11 of RGDV and actin of R. dorsalis Failure of virus-induced filaments assembly by RNA interference with synthesized double-stranded RNA targeting the Pns11 gene inhibited the dissemination of RGDV into salivary cavities, preventing viral transmission by R. dorsalis For the first time, we show that a virus can exploit virus-induced inclusion as a vehicle to pass through the apical plasmalemma into vector salivary gland cavities, thus overcoming the last membrane barrier for viral transmission by insect vectors.IMPORTANCE Understanding how persistent viruses overcome multiple tissue and membrane barriers within the insect vectors until final transmission is the key for viral disease control. The apical plasmalemma of the cavities where saliva is stored in the salivary glands is the last barrier for viral transmission by insect vectors; however, the mechanism is still poorly understood. Here we show that a virus has evolved to exploit virus-induced filaments to perform an exocytosis-like process that enables viral

  4. Persistent Histamine Excitation of Glutamatergic Preoptic Neurons

    Science.gov (United States)

    Tabarean, Iustin V.

    2012-01-01

    Thermoregulatory neurons of the median preoptic nucleus (MnPO) represent a target at which histamine modulates body temperature. The mechanism by which histamine excites a population of MnPO neurons is not known. In this study it was found that histamine activated a cationic inward current and increased the intracellular Ca2+ concentration, actions that had a transient component as well as a sustained one that lasted for tens of minutes after removal of the agonist. The sustained component was blocked by TRPC channel blockers. Single-cell reverse transcription-PCR analysis revealed expression of TRPC1, TRPC5 and TRPC7 subunits in neurons excited by histamine. These studies also established the presence of transcripts for the glutamatergic marker Vglut2 and for the H1 histamine receptor in neurons excited by histamine. Intracellular application of antibodies directed against cytoplasmic sites of the TRPC1 or TRPC5 channel subunits decreased the histamine-induced inward current. The persistent inward current and elevation in intracellular Ca2+ concentration could be reversed by activating the PKA pathway. This data reveal a novel mechanism by which histamine induces persistent excitation and sustained intracellular Ca2+ elevation in glutamatergic MnPO neurons. PMID:23082195

  5. Viral Infections and Febrile Seizures

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-01-01

    Full Text Available The incidence of febrile seizures (FS in a cohort of children, ages 3 months to 5 years, living in a Netherlands province was compared with the incidence of common viral infections reported to a national registry and the results reported from the Department of Medical Microbiology, Public Health Laboratory Friesland, Leeuwarden, The Netherlands.

  6. Viral Infection and Hepatocellular Carcinoma

    NARCIS (Netherlands)

    J. Li (Juan)

    2017-01-01

    markdownabstractMuch of liver pathology is related to infection with HBV and HCV and it is important to define factors associated with clinical behavior of disease following infection with these viruses. Thus in this thesis I first focus on the natural history of chronic viral diseases associated

  7. Viral hepatitis B- an overview

    African Journals Online (AJOL)

    1994-08-08

    Aug 8, 1994 ... Hepatitis B e antigen. (HBeAg) is a soluble non-structural, enigmatic antigen which is often detected in the blood of patients infected with replicating HBV which results in massive viral load in the blood. Both HBe and HBc are derived from the same section of HBV DNA but the HBe transcript contains an.

  8. Sustainable consumption

    DEFF Research Database (Denmark)

    Prothero, Andrea; Dobscha, Susan; Freund, Jim

    2011-01-01

    This essay explores sustainable consumption and considers possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade our planet. Future research approaches to this interdisciplinary topic need to be comprehensive...... and systematic and will benefit from a variety of different perspectives. There are a number of opportunities for future research, and three areas are explored in detail. First, the essay considers the inconsistency between the attitudes and behaviors of consumers with respect to sustainability; next, the agenda...... is broadened to explore the role of individual citizens in society; and finally, a macro institutional approach to fostering sustainability is explored. Each of these areas is examined in detail and possible research avenues and public policy initiatives are considered within each of these separate...

  9. Stabilizing Sustainability

    DEFF Research Database (Denmark)

    Reitan Andersen, Kirsti

    The publication of the Brundtland Report in 1987 put the topic of sustainable development on the political and corporate agenda. Defining sustainable development as “a development that meets the needs of the future without compromising the ability of future generations to meet their own needs......” (WCED, 1987, p. 43), the Report also put a positive spin on the issue of sustainability by upholding capitalist beliefs in the possibility of infinite growth in a world of finite resources. While growth has delivered benefits, however, it has done so unequally and unsustainably. This thesis focuses...... on the textile and fashion industry, one of the world’s most polluting industries and an industry to some degree notorious for leading the ‘race to the bottom’ in global labour standards. Despite being faced with increasing demands to practise sustainability, most textile and fashion companies continue to fail...

  10. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  11. Sustainable Cities

    DEFF Research Database (Denmark)

    Georg, Susse; Garza de Linde, Gabriela Lucía

    Judging from the number of communities and cities striving or claiming to be sustainable and how often eco-development is invoked as the means for urban regeneration, it appears that sustainable and eco-development have become “the leading paradigm within urban development” (Whitehead 2003......), urban design competitions are understudied mechanisms for bringing about field level changes. Drawing on actor network theory, this paper examines how urban design competitions may bring about changes within the professional field through the use of intermediaries such as a sustainable planning....../assessment tool. The context for our study is urban regeneration in one Danish city, which had been suffering from industrial decline and which is currently investing in establishing a “sustainable city”. Based on this case study we explore how the insights and inspiration evoked in working with the tool...

  12. Sustainable responsibilities?

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    2015-01-01

    This working paper analyzes the conceptions of corporate responsibility for sustainable development in EU policies on CSR. The notion of corporate responsibility has until recently been limited to economical and legal responsibilities. Based on this narrow conception of corporate responsibility.......e. a combination of destruction and construction, this chapter will deconstruct conceptions of responsibility for sustainable development in these EU documents on CSR. A deconstructive conceptual analysis involves destructing dominant interpretations of a text and allowing for constructions of alternative...... such as sustainability actually means, but on what the concept says and does not say. A deconstructive analysis of EU policies on CSR, then, pinpoints that such policies are sites of conceptual struggles. This kind of analysis is suitable for studying conceptions of corporate responsibility for sustainable development...

  13. Agriculture: Sustainability

    Science.gov (United States)

    Sustainability creates and maintains the conditions under which humans and nature can exist in productive harmony, that permit fulfilling the food, feed, and fiber needs of our country and the social, economic and other requirements.

  14. Mast cells in viral infections

    Directory of Open Access Journals (Sweden)

    Piotr Witczak

    2012-04-01

    Full Text Available  There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9, but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus. It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

  15. Autistic disorder and viral infections.

    Science.gov (United States)

    Libbey, Jane E; Sweeten, Thayne L; McMahon, William M; Fujinami, Robert S

    2005-02-01

    Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism.

  16. Sustainable finance

    OpenAIRE

    Boersma-de Jong, Margreet F.

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence Sustainable Business Administration & Management Accounting, Financial Leadership and what is the importance of CSR in the financial sector

  17. Determined persistence: achieving and sustaining job satisfaction among nurse practitioners.

    Science.gov (United States)

    Shea, Mary L

    2015-01-01

    Job satisfaction of nurse practitioners (NPs) has been studied using quantitative methods. A grounded theory approach was used in this study to understand the contextual nature of the NPs' description of job satisfaction from a personal perspective. A grounded theory approach as described by Glaser and Strauss was used in this study. The study took place in a rural northeastern state. The researcher conducted face-to-face interviews using open-ended questions with 15 participants. Constant comparative method was utilized to analyze data culminating in a basic social process. The participants described holistic care as the foundation of their work and their relationship with patients as determining factors of job satisfaction. When NPs felt as though patient care was compromised, they became dissatisfied. NPs were highly satisfied when providing holistic care and within an environment that respected their professional values. In order to maintain accessibility to high-quality health care, it is imperative to understand the factors that contribute to job satisfaction of NPs. As the healthcare system evolves, healthcare policymakers and healthcare organizations must develop strategies to ensure job satisfaction among NPs. ©2014 American Association of Nurse Practitioners.

  18. SUSTAINABLE TRANSPORTATION

    Directory of Open Access Journals (Sweden)

    Linda STEG

    2007-01-01

    Full Text Available This paper discusses possible contributions of psychologists to sustainable transportation. It is argued that in order to reach sustainable transportation, among others, behaviour changes of individual car users are needed. As transport policies will be more effective if they target important antecedents of travel behaviour, first, factors influencing such behaviour are discussed. It is argued that car use is very attractive and sometimes even necessary for many different reasons. This implies that a combination of policies is called for, each targeting different factors that support car use and hinder the use of more sustainable modes of transport. Next, the paper elaborates on policy strategies that may be employed to achieve sustainable transportation by changing car use. Increasing the attractiveness of sustainable transport modes by means of pull measures seems not sufficient to reduce the level of car use. Besides, car use should be made less attractive by means of push measures to force drivers to reconsider their travel behaviour. The acceptability of such policies may be increased by clearly communicating the aim of these policies, and the expected positive consequences (e.g., less congestion, improved environmental quality. Moreover, possible negative effects for individual freedom may be compensated by implementing additional policies aimed at facilitating the use of sustainable transport modes.

  19. Computing multidimensional persistence

    Directory of Open Access Journals (Sweden)

    Gunnar Carlsson

    2010-11-01

    Full Text Available The theory of multidimensional persistence captures the topology of a multifiltration - a multiparameter family of increasing spaces.  Multifiltrations arise naturally in the topological analysis of scientific data.  In this paper, we give a polynomial time algorithm for computing multidimensional persistence.  We recast this computation as a problem within computational commutative algebra and utilize algorithms from this area to solve it.  While the resulting problem is EXPSPACE-complete and the standard algorithms take doubly-exponential time, we exploit the structure inherent withing multifiltrations to yield practical algorithms.  We implement all algorithms in the paper and provide statistical experiments to demonstrate their feasibility.

  20. Persistent Hiccups Following Stapedectomy

    Directory of Open Access Journals (Sweden)

    Aidonis I

    2010-10-01

    Full Text Available Objective: We report a case of a 37 year-old man who developed persistent hiccups after elective stapedectomy. Method and Results: The diagnostic approach is discussed as well as the non-pharmacologic and pharmacologic treatments and overall management. The aim is to stress that there is a variety of potential factors that can induce hiccups perioperatively and in cases like this a step by step approach must be taken. Conclusion: Persistent hiccups are very rare following stapedectomy, control of them is crucial for the successful outcome. The trigger may be more than one factors and the good response to treatment may be due to dealing successfully with more than one thing.

  1. Persistent genital arousal disorder

    OpenAIRE

    Manju Aswath; Lakshmi V Pandit; Karthik Kashyap; Raguram Ramnath

    2016-01-01

    Persistent genital arousal disorder (PGAD) is a phenomenon, in which afflicted women experience spontaneous genital arousal, unresolved by orgasms and triggered by sexual or nonsexual stimuli, eliciting stress. The current case is a 40-year-old female who experienced such orgasms for about a month. Physical examination, investigations, and psychological testing were noncontributory. Carbamazepine (600 mg) was discontinued due to a lack of response. She improved significantly with supportive t...

  2. Persistent portal venous gas.

    Science.gov (United States)

    Huurman, Volkert A L; Visser, Leo G; Steens, Stefan C A; Terpstra, Onno T; Schaapherder, Alexander F M

    2006-05-01

    This case report describes a patient diagnosed with ongoing portal venous gas, initiated by a rather common Campylobacter enterocolitis and maintained by septic thrombophlebitis and possibly by chronic cholecystitis. Cholecystectomy attenuated the patient's septic condition. The etiology of portal venous gas determines both the patient's prognosis and the choice for either conservative or surgical treatment. This report describes persistence of portal venous gas for a long period and a possible role for chronic cholecystitis as a cause.

  3. Persistent benign pleural effusion.

    Science.gov (United States)

    Porcel, J M

    In this narrative review we describe the main aetiologies, clinical characteristics and treatment for patients with benign pleural effusion that characteristically persists over time: chylothorax and cholesterol effusions, nonexpansible lung, rheumatoid pleural effusion, tuberculous empyema, benign asbestos pleural effusion and yellow nail syndrome. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  4. Intergenerational Top Income Persistence

    DEFF Research Database (Denmark)

    Munk, Martin; Bonke, Jens; Hussain, M. Azhar

    2016-01-01

    In this paper, we investigate intergenerational top earnings and top income mobility in Denmark. Access to administrative registers allowed us to look at very small fractions of the population. We find that intergenerational mobility is lower in the top when including capital income in the income...... measure—for the rich top 0.1% fathers and sons the elasticity is 0.466. Compared with Sweden, however, the intergenerational top income persistence is about half the size in Denmark....

  5. Sustainable markets for sustainable energy

    Energy Technology Data Exchange (ETDEWEB)

    Millan, J.; Smyser, C.

    1997-12-01

    The author discusses how the Inter-American Development Bank (IDB) is involved in sustainable energy development. It presently has 50 loans and grants for non conventional renewable energy projects and ten grants for efficiency programs for $600 and $17 million respectively, representing 100 MW of power. The IDB is concerned with how to create a sustainable market for sustainable energy projects. The IDB is trying to work with government, private sector, NGOs, trading allies, credit sources, and regulators to find proper roles for such projects. He discusses how the IDB is working to expand its vision and objectives in renewable energy projects in Central and South America.

  6. Persistent trophoblastic tumors

    Directory of Open Access Journals (Sweden)

    M. N. Tikhonovskaya

    2013-01-01

    Full Text Available Persistent trophoblastic tumors (PTT are the most common trofhoblastic tumors, which develop in women when proliferative trophoblastic activ- ity remains after evacuation of hydatidiform mole. The term persistent trophoblastic disease (PTD is also widely used in the world literature. When PTD develops, new tissue is often not obtained. PTD is defined as a plateau or rise of serum β-hCG concentrations in tree subsequent weekly blood samples for 2 consecutive weeks (1, 8, 15 measurement days, the detection of β-hCG rise 6 months after hydatidiform mole evacu- ation. β-hCG is a glycoprotein hormone produced by trophoblastic tissue and a key tumor marker of gestational trophoblastic disease (GTD with almost 100 % sensitivity and specificity. A persistent trophoblastic tumor may have the histological features of invasive hydatidiform mole, cho- riocarcinoma or rare forms of trophoblastic disease. PTD is a fatal disease, which occurs in women of reproductive age. PTT is nowadays typi- cally treated with chemotherapy according to international standards for GTD management. In the case of early identification and adequate treatment of PTT the cure rates approach 100 %.

  7. Numeric invariants from multidimensional persistence

    Energy Technology Data Exchange (ETDEWEB)

    Skryzalin, Jacek [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Carlsson, Gunnar [Stanford Univ., Stanford, CA (United States)

    2017-05-19

    In this paper, we analyze the space of multidimensional persistence modules from the perspectives of algebraic geometry. We first build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence over one-dimensional persistence. We argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Lastly, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be used to study data.

  8. Non-random patterns in viral diversity

    DEFF Research Database (Denmark)

    Anthony, Simon J.; Islam, Ariful; Johnson, Christine

    2015-01-01

    It is currently unclear whether changes in viral communities will ever be predictable. Here we investigate whether viral communities in wildlife are inherently structured (inferring predictability) by looking at whether communities are assembled through deterministic (often predictable) or stocha...

  9. A stochastic model of latently infected cell reactivation and viral blip generation in treated HIV patients.

    Directory of Open Access Journals (Sweden)

    Jessica M Conway

    2011-04-01

    Full Text Available Motivated by viral persistence in HIV+ patients on long-term anti-retroviral treatment (ART, we present a stochastic model of HIV viral dynamics in the blood stream. We consider the hypothesis that the residual viremia in patients on ART can be explained principally by the activation of cells latently infected by HIV before the initiation of ART and that viral blips (clinically-observed short periods of detectable viral load represent large deviations from the mean. We model the system as a continuous-time, multi-type branching process. Deriving equations for the probability generating function we use a novel numerical approach to extract the probability distributions for latent reservoir sizes and viral loads. We find that latent reservoir extinction-time distributions underscore the importance of considering reservoir dynamics beyond simply the half-life. We calculate blip amplitudes and frequencies by computing complete viral load probability distributions, and study the duration of viral blips via direct numerical simulation. We find that our model qualitatively reproduces short small-amplitude blips detected in clinical studies of treated HIV infection. Stochastic models of this type provide insight into treatment-outcome variability that cannot be found from deterministic models.

  10. Borna Disease Virus Assembles Porous Cage-like Viral Factories in the Nucleus.

    Science.gov (United States)

    Hirai, Yuya; Hirano, Yasuhiro; Matsuda, Atsushi; Hiraoka, Yasushi; Honda, Tomoyuki; Tomonaga, Keizo

    2016-12-09

    Animal-derived RNA viruses frequently generate viral factories in infected cells. However, the details of how RNA viruses build such intracellular structures are poorly understood. In this study, we examined the structure and formation of the viral factories, called viral speckle of transcripts (vSPOTs), that are produced in the nuclei of host cells by Borna disease virus (BDV). Super-resolution microscopic analysis showed that BDV assembled vSPOTs as intranuclear cage-like structures with 59-180-nm pores. The viral nucleoprotein formed the exoskeletons of vSPOTs, whereas the other viral proteins appeared to be mainly localized within these structures. In addition, stochastic optical reconstruction microscopy revealed that filamentous structures resembling viral ribonucleoprotein complexes (RNPs) appeared to protrude from the outer surfaces of the vSPOTs. We also found that vSPOTs disintegrated into RNPs concurrently with the breakdown of the nuclear envelope during mitosis. These observations demonstrated that BDV generates viral replication factories whose shape and formation are regulated, suggesting the mechanism of the integrity of RNA virus persistent infection in the nucleus. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Borna Disease Virus Assembles Porous Cage-like Viral Factories in the Nucleus*

    Science.gov (United States)

    Hirai, Yuya; Hirano, Yasuhiro; Matsuda, Atsushi; Hiraoka, Yasushi; Honda, Tomoyuki; Tomonaga, Keizo

    2016-01-01

    Animal-derived RNA viruses frequently generate viral factories in infected cells. However, the details of how RNA viruses build such intracellular structures are poorly understood. In this study, we examined the structure and formation of the viral factories, called viral speckle of transcripts (vSPOTs), that are produced in the nuclei of host cells by Borna disease virus (BDV). Super-resolution microscopic analysis showed that BDV assembled vSPOTs as intranuclear cage-like structures with 59–180-nm pores. The viral nucleoprotein formed the exoskeletons of vSPOTs, whereas the other viral proteins appeared to be mainly localized within these structures. In addition, stochastic optical reconstruction microscopy revealed that filamentous structures resembling viral ribonucleoprotein complexes (RNPs) appeared to protrude from the outer surfaces of the vSPOTs. We also found that vSPOTs disintegrated into RNPs concurrently with the breakdown of the nuclear envelope during mitosis. These observations demonstrated that BDV generates viral replication factories whose shape and formation are regulated, suggesting the mechanism of the integrity of RNA virus persistent infection in the nucleus. PMID:27803166

  12. 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.

  13. Faktor Risiko Non Viral Pada Karsinoma Nasofaring

    Directory of Open Access Journals (Sweden)

    Sukri Rahman

    2015-09-01

    Full Text Available Abstrak           Latar belakang: Karsinoma nasofaring adalah tumor ganas epitel nasofaring yang sampai saat ini penyebabnya belum diketahui, infeksi virus Epstein Barr dilaporkan sebagai faktor dominan terjadinya karsinoma nasofaring tetapi faktor non viral juga berperan untuk timbulnya keganasan nasofaring. Tujuan: Untuk mengetahui faktor non viral  yang dapat meningkatkan kejadian karsinoma nasofaring sehingga dapat mencegah dan menghindari faktor-faktor non viral tersebut. Tinjauan Pustaka: Karsinoma nasofaring merupakan tumor ganas epitel nasofaring yang penyebabnya berhubungan dengan faktor viral dan non viral diantaranya asap rokok, ikan asin, formaldehid, genetik, asap kayu bakar , debu kayu, infeksi kronik telinga hidung tenggorok, alkohol dan obat tradisional. Kesimpulan: Pembuktian secara klinis dan ilmiah terhadap faktor non viral sebagai penyebab timbulnya karsinoma nasofaring masih belum dapat dijelaskan secara pasti. Faktor non viral merupakan salah satu faktor risiko yang dapat meningkatkan angka kejadian timbulnya keganasan nasofaring Kata kunci: karsinoma nasofaring, faktor risiko, non viral AbstractBackground: Nasopharyngeal carcinoma is a malignant epithelial nasopharyngeal tumor that until now the cause still unknown, Epstein barr virus infection had reported as predominant occurance of nasopharyngeal carcinoma but non viral factors may also contribute to the onset of the incidence of nasopharyngeal malignancy. Purpose: To find non viral factors that may increase the incidence of nasopharyngel carcinoma in order to prevent and avoid non-viral factors Literature: Nasopharyngeal carcinoma is a malignant tumor that causes nasopharyngeal epithelium associated with viral and non-viral factors such as cigarette smoke, salt fish, formaldehyde, genetic, wood smoke ,wood dust, ear nose throat chronic infections, alcohol, and traditional medicine. Conclusion: Clinically and scientifically proving the non-viral factors as

  14. Cytokine responses in acute and persistent human parvovirus B19 infection

    DEFF Research Database (Denmark)

    Isa, A; Lundqvist, A; Lindblom, A

    2007-01-01

    The aim of this study was to characterize the proinflammatory and T helper (Th)1/Th2 cytokine responses during acute parvovirus B19 (B19) infection and determine whether an imbalance of the Th1/Th2 cytokine pattern is related to persistent B19 infection. Cytokines were quantified by multiplex beads...... immunoassay in serum from B19-infected patients and controls. The cytokine responses were correlated with B19 serology, quantitative B19 DNA levels and clinical symptoms. In addition to a proinflammatory response, elevated levels of the Th1 type of cytokines interleukin (IL)-2, IL-12 and IL-15 were evident...... at time of the initial peak of B19 viral load in a few patients during acute infection. This pattern was seen in the absence of an interferon (IFN)-gamma response. During follow-up (20-130 weeks post-acute infection) some of these patients had a sustained Th1 cytokine response. The Th1 cytokine response...

  15. Trophic ecology and persistence of invasive silver carp ...

    African Journals Online (AJOL)

    sustaining feral population in an oligotrophic impoundment, Flag Boshielo Dam, in South Africa. The ability of this population to persist in a dam with low algal biomass (median annual suspended chlorophyll a = 0.08 μg l−1), and limited access to ...

  16. Mechanisms of influenza viral membrane fusion

    NARCIS (Netherlands)

    Blijleven, Jelle S; Boonstra, Sander; Onck, Patrick R; van der Giessen, Erik; van Oijen, Antoine M

    2016-01-01

    Influenza viral particles are enveloped by a lipid bilayer. A major step in infection is fusion of the viral and host cellular membranes, a process with large kinetic barriers. Influenza membrane fusion is catalyzed by hemagglutinin (HA), a class I viral fusion protein activated by low pH. The exact

  17. Viral commercials: the consumer as marketeer

    NARCIS (Netherlands)

    Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

    2010-01-01

    Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers,

  18. Virale commercials: De consument als marketeer

    NARCIS (Netherlands)

    Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

    2010-01-01

    Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers,

  19. Viral ecology of a shallow eutrophic lake

    NARCIS (Netherlands)

    Tijdens, M.

    2007-01-01

    This thesis aims to give an insight into the ecology of the viral community in a shallow eutrophic lake. To achieve this, the population dynamics, diversity and control of the viral community in Lake Loosdrecht were studied, as well as the impact of the viral community on plankton mortality and

  20. 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.

  1. APLASTIC ANEMIA AND VIRAL HEPATITIS

    Directory of Open Access Journals (Sweden)

    Laura Cudillo

    2009-11-01

    Liver histology is characterized by T cell infiltrating the parenchyma as reported in acute hepatitis. Recently in HAA it has been demonstrated intrahepatic  and blood lymphocytes with  T cell repertoire similar to that of confirmed viral acute hepatitis. The expanded T cell clones return to a normal distribution after response to immunosuppressive treatment, suggesting the antigen or T cell clearance. Therapeutic options are the same as acquired aplastic anemia.

  2. Treatment of Acute Viral Bronchiolitis

    Science.gov (United States)

    Eber, Ernst

    2011-01-01

    Acute viral bronchiolitis represents the most common lower respiratory tract infection in infants and young children and is associated with substantial morbidity and mortality. Respiratory syncytial virus is the most frequently identified virus, but many other viruses may also cause acute bronchiolitis. There is no common definition of acute viral bronchiolitis used internationally, and this may explain part of the confusion in the literature. Most children with bronchiolitis have a self limiting mild disease and can be safely managed at home with careful attention to feeding and respiratory status. Criteria for referral and admission vary between hospitals as do clinical practice in the management of acute viral bronchiolitis, and there is confusion and lack of evidence over the best treatment for this condition. Supportive care, including administration of oxygen and fluids, is the cornerstone of current treatment. The majority of infants and children with bronchiolitis do not require specific measures. Bronchodilators should not be routinely used in the management of acute viral bronchiolitis, but may be effective in some patients. Most of the commonly used management modalities have not been shown to have a clear beneficial effect on the course of the disease. For example, inhaled and systemic corticosteroids, leukotriene receptor antagonists, immunoglobulins and monoclonal antibodies, antibiotics, antiviral therapy, and chest physiotherapy should not be used routinely in the management of bronchiolitis. The potential effect of hypertonic saline on the course of the acute disease is promising, but further studies are required. In critically ill children with bronchiolitis, today there is little justification for the use of surfactant and heliox. Nasal continuous positive airway pressure may be beneficial in children with severe bronchiolitis but a large trial is needed to determine its value. Finally, very little is known on the effect of the various

  3. Viral exanthems in the tropics.

    Science.gov (United States)

    Carneiro, Sueli Coelho da Silva; Cestari, Tania; Allen, Samuel H; Ramos e-Silva, Marcia

    2007-01-01

    Viral exanthems are a common problem in tropical regions, particularly affecting children. Most exanthems are transient and harmless, but some are potentially very dangerous. Pregnant women and malnourished or immunocompromised infants carry the greatest risk of adverse outcome. In this article, parvovirus B19; dengue and yellow fever; West Nile, Barmah Forest, Marburg, and Ebola viruses, and human herpesviruses; asymmetric periflexural exanthema of childhood; measles; rubella; enteroviruses; Lassa fever; and South American hemorrhagic fevers will be discussed.

  4. Roundtabling Sustainability

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2014-01-01

    The willingness of public authority to delegate social and environmental regulation to the private sector has varied from sector to sector, but has often led to the establishment of ‘voluntary’ standards and certifications on sustainability. Many of these have taken the form of ‘stewardship...... councils’ and ‘sustainability roundtables’ and have been designed around a set of institutional features seeking to establish legitimacy, fend off possible criticism, and ‘sell’ certifications to potential users. The concept of ‘roundtabling’ emphasizes the fitting a variety of commodity......-specific sustainability situations into a form that not only ‘hears more voices’ (as in ‘multi-stakeholder’), but also portrays to give them equal standing at the table of negotiations (roundtable), thus raising higher expectations on accountability, transparency and inclusiveness. In this article, I examine to what...

  5. Recycling Endosomes and Viral Infection

    Directory of Open Access Journals (Sweden)

    Sílvia Vale-Costa

    2016-03-01

    Full Text Available Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral–host interactions occurring on the endocytic recycling compartment (ERC, and mediated by its regulatory Ras-related in brain (Rab GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition.

  6. Maternal immunization against viral disease.

    Science.gov (United States)

    Englund, J; Glezen, W P; Piedra, P A

    1998-01-01

    The protective effect of maternal antibody against many viral diseases has been recognized. The use of maternal immunization has been considered as a means to augment this protection in the young infant against disease. Advantages of maternal immunization include the fact that young infants are most susceptible to infections but least responsive to vaccines, that pregnant women are accessible to medical care and respond well to vaccines, that IgG antibodies cross the placenta well during the third trimester, and that immunization of the pregnant woman has the potential to benefit both the mother and the infant. Disadvantages include the potential inhibition of an infant's response to active immunization or natural infection and liability issues with pharmaceutical companies and physicians. Immunization of pregnant women with viral vaccines for poliovirus, influenza viruses, and rubella has been described and maternal vaccination with these vaccines has been found to be safe for both the mother and the fetus. An open-label study of post-partum women immunized with the purified fusion protein of RSV (PFP-2, Wyeth-Lederle Pediatrics and Vaccines, Inc., Pearl River, NY) demonstrated that the vaccine was non-reactogenic and immunogenic; RSV-specific antibody was detected in breast milk. Immunization of pregnant women with purified protein or subunit vaccines could be considered against neonatal viral pathogens, such as respiratory syncytial virus, parainfluenza viruses, herpes group viruses, and human immunodeficiency virus. Further studies are needed to define the safety and efficacy of maternal immunization.

  7. Pediatric Asthma and Viral Infection.

    Science.gov (United States)

    Garcia-Garcia, M Luz; Calvo Rey, Cristina; Del Rosal Rabes, Teresa

    2016-05-01

    Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma. Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.

  8. Sustainability Evaluation.

    Science.gov (United States)

    Stichnothe, Heinz

    2017-03-17

    The long-term substitution of fossil resources can only be achieved through a bio-based economy, with biorefineries and bio-based products playing a major role. However, it is important to assess the implications of the transition to a bio-based economy. Life cycle-based sustainability assessment is probably the most suitable approach to quantify impacts and to identify trade-offs at multiple levels. The extended utilisation of biomass can cause land use change and affect food security of the most vulnerable people throughout the world. Although this is mainly a political issue and governments should be responsible, the responsibility is shifted to companies producing biofuels and other bio-based products. Organic wastes and lignocellulosic biomass are considered to be the preferred feedstock for the production of bio-based products. However, it is unlikely that a bio-based economy can rely only on organic wastes and lignocellulosic biomass.It is crucial to identify potential problems related to socio-economic and environmental issues. Currently there are many approaches to the sustainability of bio-based products, both quantitative and qualitative. However, results of different calculation methods are not necessarily comparable and can cause confusion among decision-makers, stakeholders and the public.Hence, a harmonised, globally agreed approach would be the best solution to secure sustainable biomass/biofuels/bio-based chemicals production and trade, and to avoid indirect effects (e.g. indirect land use change). However, there is still a long way to go.Generally, the selection of suitable indicators that serve the purpose of sustainability assessment is very context-specific. Therefore, it is recommended to use a flexible and modular approach that can be adapted to various purposes. A conceptual model for the selection of sustainability indicators is provided that facilitates identifying suitable sustainability indicators based on relevance and significance in a

  9. Evaluation of persistence of resistant variants with ultra-deep pyrosequencing in chronic hepatitis C patients treated with telaprevir.

    Directory of Open Access Journals (Sweden)

    Xiomara V Thomas

    Full Text Available BACKGROUND & AIMS: Telaprevir, a hepatitis C virus NS3/4A protease inhibitor has significantly improved sustained viral response rates when given in combination with pegylated interferon alfa-2a and ribavirin, compared with current standard of care in hepatitis C virus genotype 1 infected patients. In patients with a failed sustained response, the emergence of drug-resistant variants during treatment has been reported. It is unclear to what extent these variants persist in untreated patients. The aim of this study was to assess using ultra-deep pyrosequencing, whether after 4 years follow-up, the frequency of resistant variants is increased compared to pre-treatment frequencies following 14 days of telaprevir treatment. METHODS: Fifteen patients from 2 previous telaprevir phase 1 clinical studies (VX04-950-101 and VX05-950-103 were included. These patients all received telaprevir monotherapy for 14 days, and 2 patients subsequently received standard of care. Variants at previously well-characterized NS3 protease positions V36, T54, R155 and A156 were assessed at baseline and after a follow-up of 4±1.2 years by ultra-deep pyrosequencing. The prevalence of resistant variants at follow-up was compared to baseline. RESULTS: Resistance associated mutations were detectable at low frequency at baseline. In general, prevalence of resistance mutations at follow-up was not increased compared to baseline. Only one patient had a small, but statistically significant, increase in the number of V36M and T54S variants 4 years after telaprevir-dosing. CONCLUSION: In patients treated for 14 days with telaprevir monotherapy, ultra-deep pyrosequencing indicates that long-term persistence of resistant variants is rare.

  10. Modoc Viral Infections in the Deer Mouse Peromyscus maniculatus

    Science.gov (United States)

    Davis, James W.; Hardy, James L.; Reeves, William C.

    1974-01-01

    The pathogenesis of Modoc virus and its mechanism of transmission were investigated in Peromyscus maniculatus gambeli (deer mouse) as a model to understand the natural history of this virus. Animals were readily infected by the intranasal or subcutaneous route of inoculation. Virus could be detected by direct isolation techniques in many organs and body fluids during the first 7 to 9 days after intranasal inoculation. Increases in viral titers were detectable first in lungs and then the spleen, salivary-submaxillary glands, and lymph nodes. Viremias were low titered and ephemeral. Virus was recovered from urine and throat swabs 4 to 6 days and 4 to 7 days after inoculation, respectively. Serum dilution neutralization, hemagglutination inhibition, or complement fixation antibodies were detected in sera of some animals 13 days after infection and in all animals after 20 days. Antibodies persisted for the 168-day period of observation. Persistent viral infection was demonstrable by in vitro culturing of lungs or pooled lungs, salivary glands, and kidneys from 14 of 69 mice that were sacrificed from 1 to 6 months after intranasal inoculation. Attempts to demonstrate horizontal or vertical transmission of Modoc virus among mice were generally unsuccessful. Female deer mice infected with virus before mating passed maternal antibodies to their young. PMID:4215763

  11. Hepatitis A virus-encoded miRNAs attenuate the accumulation of viral genomic RNAs in infected cells.

    Science.gov (United States)

    Shi, Jiandong; Sun, Jing; Wu, Meini; Hu, Ningzhu; Hu, Yunzhang

    2016-06-01

    The establishment of persistent infection with hepatitis A virus (HAV) is the common result of most HAV/cell culture systems. Previous observations show that the synthesis of viral RNAs is reduced during infection. However, the underlying mechanism is poorly understood. We characterized three HAV-encoded miRNAs in our previous study. In this study, we aim to investigate the impact of these miRNAs on the accumulation of viral RNAs. The results indicated that the synthesis of viral genomic RNAs was dramatically reduced (more than 75 % reduction, P virus-derived miRNA could serve as a self-mediated feedback regulator during infection.

  12. Visualizing viral dissemination in the mouse nervous system, using a green fluorescent protein-expressing Borna disease virus vector.

    Science.gov (United States)

    Ackermann, Andreas; Guelzow, Timo; Staeheli, Peter; Schneider, Urs; Heimrich, Bernd

    2010-05-01

    Borna disease virus (BDV) frequently persists in the brain of infected animals. To analyze viral dissemination in the mouse nervous system, we generated a mouse-adapted virus that expresses green fluorescent protein (GFP). This viral vector supported GFP expression for up to 150 days and possessed an extraordinary staining capacity, visualizing complete dendritic arbors as well as individual axonal fibers of infected neurons. GFP-positive cells were first detected in cortical areas from where the virus disseminated through the entire central nervous system (CNS). Late in infection, GFP expression was found in the sciatic nerve, demonstrating viral spread from the central to the peripheral nervous system.

  13. Emerging viral diseases of fish and shrimp

    Science.gov (United States)

    Winton, James R.; Walker, Peter J.

    2010-01-01

    The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change.

  14. Viral Hepatitis: Information for Gay and Bisexual Men

    Science.gov (United States)

    VIRAL HEPATITIS Information for Gay and Bisexual Men What is viral hepatitis? Viral hepatitis is an infection of the liver caused by ... United States, the most common types of viral hepatitis are Hepatitis A, Hepatitis B, and Hepatitis C. ...

  15. Persistence of airline accidents.

    Science.gov (United States)

    Barros, Carlos Pestana; Faria, Joao Ricardo; Gil-Alana, Luis Alberiko

    2010-10-01

    This paper expands on air travel accident research by examining the relationship between air travel accidents and airline traffic or volume in the period from 1927-2006. The theoretical model is based on a representative airline company that aims to maximise its profits, and it utilises a fractional integration approach in order to determine whether there is a persistent pattern over time with respect to air accidents and air traffic. Furthermore, the paper analyses how airline accidents are related to traffic using a fractional cointegration approach. It finds that airline accidents are persistent and that a (non-stationary) fractional cointegration relationship exists between total airline accidents and airline passengers, airline miles and airline revenues, with shocks that affect the long-run equilibrium disappearing in the very long term. Moreover, this relation is negative, which might be due to the fact that air travel is becoming safer and there is greater competition in the airline industry. Policy implications are derived for countering accident events, based on competition and regulation. © 2010 The Author(s). Journal compilation © Overseas Development Institute, 2010.

  16. Six persistent research misconceptions.

    Science.gov (United States)

    Rothman, Kenneth J

    2014-07-01

    Scientific knowledge changes rapidly, but the concepts and methods of the conduct of research change more slowly. To stimulate discussion of outmoded thinking regarding the conduct of research, I list six misconceptions about research that persist long after their flaws have become apparent. The misconceptions are: 1) There is a hierarchy of study designs; randomized trials provide the greatest validity, followed by cohort studies, with case-control studies being least reliable. 2) An essential element for valid generalization is that the study subjects constitute a representative sample of a target population. 3) If a term that denotes the product of two factors in a regression model is not statistically significant, then there is no biologic interaction between those factors. 4) When categorizing a continuous variable, a reasonable scheme for choosing category cut-points is to use percentile-defined boundaries, such as quartiles or quintiles of the distribution. 5) One should always report P values or confidence intervals that have been adjusted for multiple comparisons. 6) Significance testing is useful and important for the interpretation of data. These misconceptions have been perpetuated in journals, classrooms and textbooks. They persist because they represent intellectual shortcuts that avoid more thoughtful approaches to research problems. I hope that calling attention to these misconceptions will spark the debates needed to shelve these outmoded ideas for good.

  17. Molecular mechanisms underlying bacterial persisters

    DEFF Research Database (Denmark)

    Maisonneuve, Etienne; Gerdes, Kenn

    2014-01-01

    All bacteria form persisters, cells that are multidrug tolerant and therefore able to survive antibiotic treatment. Due to the low frequencies of persisters in growing bacterial cultures and the complex underlying molecular mechanisms, the phenomenon has been challenging to study. However, recent...... technological advances in microfluidics and reporter genes have improved this scenario. Here, we summarize recent progress in the field, revealing the ubiquitous bacterial stress alarmone ppGpp as an emerging central regulator of multidrug tolerance and persistence, both in stochastically and environmentally...... induced persistence. In several different organisms, toxin-antitoxin modules function as effectors of ppGpp-induced persistence....

  18. Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence duringin vivopassage.

    Science.gov (United States)

    Peña, José; Chen-Harris, Haiyin; Allen, Jonathan E; Hwang, Mona; Elsheikh, Maher; Mabery, Shalini; Bielefeldt-Ohmann, Helle; Zemla, Adam T; Bowen, Richard A; Borucki, Monica K

    2016-01-01

    In vivo serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregulated immune response and can increase viral mutant spectrum diversity and virulence. The objective of this study was to identify the role of viral mutant spectra dynamics and host immunocompetence in the development of pathogenicity during in vivo passage. Because the nutritional status of the host has been shown to affect the development of viral virulence, the diet of animal model reflected two extremes of diets which exist in the global population, malnutrition and obesity. Sendai virus was serially passaged in groups of mice with differing nutritional status followed by transmission of the passaged virus to a second host species, guinea pigs. Viral population dynamics were characterized using deep sequence analysis and computational modeling. Histopathology, viral titer and cytokine assays were used to characterize viral virulence. Viral virulence increased with passage and the virulent phenotype persisted upon passage to a second host species. Additionally, nutritional status of mice during passage influenced the phenotype. Sequencing revealed the presence of several non-synonymous changes in the consensus sequence associated with passage, a majority of which occurred in the hemagglutinin-neuraminidase and polymerase genes, as well as the presence of persistent high frequency variants in the viral population. In particular, an N1124D change in the consensus sequences of the polymerase gene was detected by passage 10 in a majority of the animals. In vivo comparison of an 1124D plaque isolate to a clone with 1124N genotype indicated that 1124D was associated with increased virulence.

  19. Sustainable Soesterkwartier

    NARCIS (Netherlands)

    Abrahams, H.; Goosen, H.; Jong, de F.; Sickmann, J.; Prins, D.

    2010-01-01

    The municipality of Amersfoort wants to construct an endurable and sustainable eco-town in the Soesterkwartier neighbourhood, by taking future climate change into account. The impact of climate change at the location of the proposed eco-town was studied by a literature review.

  20. Sustainable agriculture

    International Development Research Centre (IDRC) Digital Library (Canada)

    New farming techniques, better food security. Since 1970, IDRC-supported research has introduced sustainable agricultural practices to farmers and communities across the devel- oping world. The result: higher productivity, less poverty, greater food security, and a healthier environment. Opportunities grow on trees in ...

  1. Sustainable Development

    African Journals Online (AJOL)

    Tsegai Berhane Ghebretekle

    Abstract. This article examines the concept of sustainable development after the Post-. 2015 Paris Climate Change Agreement with particular emphasis on Ethiopia. Various African countries are vulnerable to climate change, as is evidenced by recent droughts. Ethiopia is selected as a case study in light of its pace in.

  2. Sustainable machining

    CERN Document Server

    2017-01-01

    This book provides an overview on current sustainable machining. Its chapters cover the concept in economic, social and environmental dimensions. It provides the reader with proper ways to handle several pollutants produced during the machining process. The book is useful on both undergraduate and postgraduate levels and it is of interest to all those working with manufacturing and machining technology.

  3. Architecture Sustainability

    NARCIS (Netherlands)

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

    Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The

  4. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. It The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  5. Sustainable processing

    DEFF Research Database (Denmark)

    Kristensen, Niels Heine

    2004-01-01

    Kristensen_NH and_Beck A: Sustainable processing. In Otto Schmid, Alexander Beck and Ursula Kretzschmar (Editors) (2004): Underlying Principles in Organic and "Low-Input Food" Processing - Literature Survey. Research Institute of Organic Agriculture FiBL, CH-5070 Frick, Switzerland. ISBN 3-906081-58-3...

  6. Sustainable finance

    NARCIS (Netherlands)

    dr. Margreet F. Boersma-de Jong

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence

  7. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies.

    Directory of Open Access Journals (Sweden)

    Susanne Eriksson

    2013-02-01

    Full Text Available HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy (HAART. The best characterized reservoir is a small, difficult-to-quantify pool of resting memory CD4(+ T cells carrying latent but replication-competent viral genomes. Because strategies targeting this latent reservoir are now being tested in clinical trials, well-validated high-throughput assays that quantify this reservoir are urgently needed. Here we compare eleven different approaches for quantitating persistent HIV-1 in 30 patients on HAART, using the original viral outgrowth assay for resting CD4(+ T cells carrying inducible, replication-competent viral genomes as a standard for comparison. PCR-based assays for cells containing HIV-1 DNA gave infected cell frequencies at least 2 logs higher than the viral outgrowth assay, even in subjects who started HAART during acute/early infection. This difference may reflect defective viral genomes. The ratio of infected cell frequencies determined by viral outgrowth and PCR-based assays varied dramatically between patients. Although strong correlations with the viral outgrowth assay could not be formally excluded for most assays, correlations achieved statistical significance only for integrated HIV-1 DNA in peripheral blood mononuclear cells and HIV-1 RNA/DNA ratio in rectal CD4(+ T cells. Residual viremia was below the limit of detection in many subjects and did not correlate with the viral outgrowth assays. The dramatic differences in infected cell frequencies and the lack of a precise correlation between culture and PCR-based assays raise the possibility that the successful clearance of latently infected cells may be masked by a larger and variable pool of cells with defective proviruses. These defective proviruses are detected by PCR but may not be affected by reactivation strategies and may not require eradication to accomplish an effective cure. A molecular understanding of the discrepancy

  8. Sustainability, Indicators, and Institutions of Higher Education. Chapter 42

    Science.gov (United States)

    Indicators of commitment to sustainability commonly applied to institutions of higher education provide no estimate of the actual effects that these institutions have on the persistence or prevalence of the socioecological systems that encompass them. Emergy methodology provides ...

  9. Borna disease virus phosphoprotein modulates epigenetic signaling in neurons to control viral replication.

    Science.gov (United States)

    Bonnaud, Emilie M; Szelechowski, Marion; Bétourné, Alexandre; Foret, Charlotte; Thouard, Anne; Gonzalez-Dunia, Daniel; Malnou, Cécile E

    2015-06-01

    Understanding the modalities of interaction of neurotropic viruses with their target cells represents a major challenge that may improve our knowledge of many human neurological disorders for which viral origin is suspected. Borna disease virus (BDV) represents an ideal model to analyze the molecular mechanisms of viral persistence in neurons and its consequences for neuronal homeostasis. It is now established that BDV ensures its long-term maintenance in infected cells through a stable interaction of viral components with the host cell chromatin, in particular, with core histones. This has led to our hypothesis that such an interaction may trigger epigenetic changes in the host cell. Here, we focused on histone acetylation, which plays key roles in epigenetic regulation of gene expression, notably for neurons. We performed a comparative analysis of histone acetylation patterns of neurons infected or not infected by BDV, which revealed that infection decreases histone acetylation on selected lysine residues. We showed that the BDV phosphoprotein (P) is responsible for these perturbations, even when it is expressed alone independently of the viral context, and that this action depends on its phosphorylation by protein kinase C. We also demonstrated that BDV P inhibits cellular histone acetyltransferase activities. Finally, by pharmacologically manipulating cellular acetylation levels, we observed that inhibiting cellular acetyl transferases reduces viral replication in cell culture. Our findings reveal that manipulation of cellular epigenetics by BDV could be a means to modulate viral replication and thus illustrate a fascinating example of virus-host cell interaction. Persistent DNA viruses often subvert the mechanisms that regulate cellular chromatin dynamics, thereby benefitting from the resulting epigenetic changes to create a favorable milieu for their latent and persistent states. Here, we reasoned that Borna disease virus (BDV), the only RNA virus known to

  10. Encefalitis virales en la infancia

    Directory of Open Access Journals (Sweden)

    Monserrat Téllez de Meneses

    2013-09-01

    Full Text Available La encefalitis viral es una enfermedad grave que implica el compromiso inflamatorio del parénquima cerebral. Las infecciones virales del SNC ocurren con frecuencia como complicación de infecciones virales sistémicas. Más de 100 virus están implicados como agentes causales, entre los cuales el virus Herpes simplex tipo I, es el agente causal más frecuente de encefalitis no epidémica en todos los grupos poblacionales del mundo; es el responsable de los casos más graves en todas las edades. Muchos de los virus para los cuales existe vacunas también pueden causar encefalitis como: sarampión, paperas, polio, rabia, rubéola, varicela. El virus produce una inflamación del tejido cerebral, la cual puede evolucionar a una destrucción de neuronas, provocar hemorragia y daño cerebral, dando lugar a encefalitis graves, como la encefalitis necrotizante o hemorrágica, con mucho peor pronóstico, produciendo secuelas graves, incluso la muerte. El cuadro clínico, incluye la presencia de cefalea, fiebre y alteración de la conciencia, de rápida progresión. El pronóstico de las encefalitis víricas es variable, algunos casos son leves, con recuperación completa, sin embargo existen casos graves que pueden ocasionar secuelas importantes a nivel cerebral. Es fundamental realizar un diagnóstico lo antes posible, a través de pruebas de laboratorio (bioquímica, PCR, cultivos y de neuroimagen (TAC, RM y ante todo, la instauración de un tratamiento precoz para evitar la evolución del proceso y sus posibles complicaciones. El pronóstico empeora si se retrasa la instauración del tratamiento.

  11. Evaluation of Viral Meningoencephalitis Cases

    Directory of Open Access Journals (Sweden)

    Handan Ilhan

    2012-08-01

    Full Text Available AIM: To evaluate retrospectively adult cases of viral encephalitis. METHOD: Fifteen patients described viral encephalitis hospitalized between the years 2006-2011 follow-up and treatment at the infectious diseases clinic were analyzed retrospectively. RESULTS: Most of the patients (%60 had applied in the spring. Fever (87%, confusion (73%, neck stiffness (73%, headache (73%, nausea-vomiting (33%, loss of consciousness (33%, amnesia (33%, agitation (20%, convulsion (%20, focal neurological signs (13%, Brudzinski-sign (13% were most frequently encountered findings. Electroencephalography test was applied to 13 of 14 patients, and pathological findings compatible with encephalitis have been found. Radiological imaging methods such as CT and MRI were performed in 9 of the 14 patients, and findings consistent with encephalitis were reported. All of initial cerebrospinal fluid (CSF samples were abnormal. The domination of the first examples was lymphocytes in 14 patients; only one patient had an increase in neutrophilic cells have been found. CSF protein level was high in nine patients, and low glucose level was detected in two patients. Herpes simplex virus polymerized chain reaction (PCR analyze was performed to fourteen patients CSF. Only two of them (14% were found positive. One of the patients sample selectively examined was found to be Parvovirus B19 (+, the other patient urine sample Jacobs-creutzfeld virus PCR was found to be positively. Empiric acyclovir therapy was given to all patients. Neuropsychiatric squeal developed at the one patient. CONCLUSION: The cases in the forefront of change in mental status viral meningoencephalitis should be considered and empirical treatment with acyclovir should be started. [TAF Prev Med Bull 2012; 11(4.000: 447-452

  12. Caliber-Persistent Artery

    Directory of Open Access Journals (Sweden)

    Sabrina Araújo Pinho Costa

    2015-01-01

    Full Text Available Caliber-persistent artery (CPLA of the lip is a common vascular anomaly in which a main arterial branch extends to the surface of the mucous tissue with no reduction in its diameter. It usually manifests as pulsatile papule, is easily misdiagnosed, and is observed more frequently among older people, suggesting that its development may involve a degenerative process associated with aging; CPLA is also characterized by the loss of tone of the adjacent supporting connective tissue. Although the diagnosis is clinical, high-resolution Doppler ultrasound is a useful noninvasive tool for evaluating the lesion. This report describes the case of a 58-year-old male patient who complained of a lesion of the lower lip with bleeding and recurrent ulceration. The patient was successfully treated in our hospital after a diagnosis of CPLA and is currently undergoing a clinical outpatient follow-up with no complaints.

  13. Persistently elevated alkaline phosphatase.

    Science.gov (United States)

    Verma, Jitin; Gorard, David A

    2012-08-24

    A 32-year-old overweight asymptomatic man was found to have a persistently raised serum alkaline phosphatase at 250-300 U/l (normal range liver function tests were unremarkable apart from an initial marginally elevated alanine transaminase, which normalised with weight reduction. Abdominal imaging revealed a fatty liver but an extensive serological search for significant hepatobiliary disease was negative. Subsequent isoenzyme electrophoresis revealed normal liver and bone fractions of alkaline phosphatase but a grossly elevated intestinal fraction. Elevated intestinal fraction of alkaline phosphatase should be considered in the investigation of unexplained alkaline phosphatase, particularly when the usual associated hepatobiliary and bony pathologies are not present. Although an elevated intestinal fraction of alkaline phosphatase can be linked to significant gastrointestinal pathology, this case report highlights that it can be a benign biochemical finding.

  14. Actionable Persistent Identifier Collections

    Directory of Open Access Journals (Sweden)

    Tobias Weigel

    2014-01-01

    Full Text Available Persistent Identifiers (PIDs have lately received a lot of attention from scientific infrastructure projects and communities that aim to employ them for management of massive amounts of research data and metadata objects. Such usage scenarios, however, require additional facilities to enable automated data management with PIDs. In this article, we present a conceptual framework that is based on the idea of using common abstract data types (ADTs in combination with PIDs. This provides a well-defined interface layer that abstracts from both underlying PID systems and higher-level applications. Our practical implementation is based on the Handle System, yet the fundamental concept of PID-based ADTs is transferable to other infrastructures, and it is well suited to achieve interoperability between them.

  15. Persistent Aerial Tracking

    KAUST Repository

    Mueller, Matthias

    2016-04-13

    In this thesis, we propose a new aerial video dataset and benchmark for low altitude UAV target tracking, as well as, a photo-realistic UAV simulator that can be coupled with tracking methods. Our benchmark provides the rst evaluation of many state of-the-art and popular trackers on 123 new and fully annotated HD video sequences captured from a low-altitude aerial perspective. Among the compared trackers, we determine which ones are the most suitable for UAV tracking both in terms of tracking accuracy and run-time. We also present a simulator that can be used to evaluate tracking algorithms in real-time scenarios before they are deployed on a UAV "in the field", as well as, generate synthetic but photo-realistic tracking datasets with free ground truth annotations to easily extend existing real-world datasets. Both the benchmark and simulator will be made publicly available to the vision community to further research in the area of object tracking from UAVs. Additionally, we propose a persistent, robust and autonomous object tracking system for unmanned aerial vehicles (UAVs) called Persistent Aerial Tracking (PAT). A computer vision and control strategy is applied to a diverse set of moving objects (e.g. humans, animals, cars, boats, etc.) integrating multiple UAVs with a stabilized RGB camera. A novel strategy is employed to successfully track objects over a long period, by \\'handing over the camera\\' from one UAV to another. We integrate the complete system into an off-the-shelf UAV, and obtain promising results showing the robustness of our solution in real-world aerial scenarios.

  16. SUSTAINABLE CORPORATE AND SUSTAINABLE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    DORU CÎRNU

    2017-06-01

    Full Text Available In recent decades, the image of the international business environment has changed significantly. Studies conducted by UNCTAD shows that corporate phenomenon developments in the world economy is growing. Without claiming to present an exhaustive topic so vast we tried to capture some "facets" of sustainable development from the perspective of multinational corporations, given the expansion of these economic entities and strengthening their power in the global economy. We present more negative aspects of the actions of multinational corporations in terms of sustainable development, it is very important to know both sides of the coin, which will not only help transnational giants including release. Based on issues such as corporate social responsibility, environmental pollution and workers' rights, we sought to counter official statements. The conclusion is that these economic entities are real forces that can not be ignored in today's world and the obvious problem of sustainable development can not be addressed independently of the phenomenon, context we also identified some possible solutions to conflict of corporations and essence of the concept of sustainable development.

  17. Non-Viral Deoxyribonucleoside Kinases

    DEFF Research Database (Denmark)

    Christiansen, Louise Slot; Munch-Petersen, Birgitte; Knecht, Wolfgang

    2015-01-01

    to be valuable in studying the evolution of enzymes. Some of these newly discovered enzymes have been useful in numerous practical applications in medicine and biotechnology, and have contributed to our understanding of the structural basis of nucleoside and nucleoside analogue activation....... of great medical interest. However, during the last 20 years, research on dNKs has gone into non-mammalian organisms. In this review, we focus on non-viral dNKs, in particular their diversity and their practical applications. The diversity of this enzyme family in different organisms has proven...

  18. Sustainable Consumption

    DEFF Research Database (Denmark)

    Røpke, Inge

    2015-01-01

    in wider social, economic and technological frameworks is emphasised. In particular, the chapter is inspired by practice theory and transition theory. First, various trends in consumption are outlined to highlight some of the challenges for sustainability transitions. Then, it is discussed how consumption...... patterns are shaped over time and what should be considered in sustainability strategies. While discussions on consumption often take their point of departure in the perspective of the individual and then zoom to the wider context, the present approach is the opposite. The outline starts with the basic...... biophysical, distributional and economic conditions for high consumption in rich countries and then zooms in on the coevolution of provision systems and consumption, and how consumption is shaped by practices and projects in everyday life. Furthermore, the paper discusses whether and how transition...

  19. Sustainable Buildings

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Elle, Morten

    The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems that ...... that need urgent action. The built environment is an obvious area to put effort into because of the large and cost-effective energy saving potential and potential for Renewable Energy-based supply systems for buildings.......The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems...

  20. Influence of temperature on viral hemorrhagic septicemia (Genogroup IVa) in Pacific herring, Clupea pallasii Valenciennes

    Science.gov (United States)

    Hershberger, P.K.; Purcell, M.K.; Hart, L.M.; Gregg, J.L.; Thompson, R.L.; Garver, K.A.; Winton, J.R.

    2013-01-01

    An inverse relationship between water temperature and susceptibility of Pacific herring (Clupea pallasii) to viral hemorrhagic septicemia, genogroup IVa (VHS) was indicated by controlled exposure studies where cumulative mortalities, viral shedding rates, and viral persistence in survivors were greatest at the coolest exposure temperatures. Among groups of specific pathogen-free (SPF) Pacific herring maintained at 8, 11, and 15 °C, cumulative mortalities after waterborne exposure to viral hemorrhagic septicemia virus (VHSV) were 78%, 40%, and 13%, respectively. The prevalence of survivors with VHSV-positive tissues 25 d post-exposure was 64%, 16%, and 0% (at 8, 11 and 15 °C, respectively) with viral prevalence typically higher in brain tissues than in kidney/spleen tissue pools at each temperature. Similarly, geometric mean viral titers in brain tissues and kidney/spleen tissue pools decreased at higher temperatures, and kidney/spleen titers were generally 10-fold lower than those in brain tissues at each temperature. This inverse relationship between temperature and VHS severity was likely mediated by an enhanced immune response at the warmer temperatures, where a robust type I interferon response was indicated by rapid and significant upregulation of the herring Mx gene. The effect of relatively small temperature differences on the susceptibility of a natural host to VHS provides insights into conditions that preface periodic VHSV epizootics in wild populations throughout the NE Pacific.

  1. Activating KIRs and NKG2C in Viral Infections: Toward NK Cell Memory?

    Science.gov (United States)

    Della Chiesa, Mariella; Sivori, Simona; Carlomagno, Simona; Moretta, Lorenzo; Moretta, Alessandro

    2015-01-01

    Natural killer (NK) cells are important players in the immune defense against viral infections. The contribution of activating killer immunoglobulin-like receptors (KIRs) and CD94/NKG2C in regulating anti-viral responses has recently emerged. Thus, in the hematopoietic stem cell transplantation setting, the presence of donor activating KIRs (aKIRs) may protect against viral infections, while in HIV-infected individuals, KIR3DS1, in combination with HLA-Bw4-I80, results in reduction of viral progression. Since, studies have been performed mainly at the genetic or transcriptional level, the effective size, the function, and the “licensing” status of NK cells expressing aKIRs, as well as the nature of their viral ligands, require further investigation. Certain viral infections, mainly due to Human cytomegalovirus (HCMV), can deeply influence the NK cell development and function by inducing a marked expansion of mature NKG2C+ NK cells expressing self-activating KIRs. This suggests that NKG2C and/or aKIRs are involved in the selective proliferation of this subset. The persistent, HCMV-induced, imprinting suggests that NK cells may display unexpected adaptive immune traits. The role of aKIRs and NKG2C in regulating NK cell responses and promoting a memory-like response to certain viruses is discussed. PMID:26617607

  2. Persistent Identifiers for Dutch cultural heritage institutions

    Science.gov (United States)

    Ras, Marcel; Kruithof, Gijsbert

    2016-04-01

    Over the past years, more and more collections belonging to archives, libraries, media, museums, and knowledge institutes are being digitised and made available online. These are exciting times for ALM institutions. They are realising that, in the information society, their collections are goldmines. Unfortunately most heritage institutions in the Netherlands do not yet meet the basic preconditions for long-term availability of their collections. The digital objects often have no long lasting fixed reference yet. URL's and web addresses change. Some digital objects that were referenced in Europeana and other portals can no longer be found. References in scientific articles have a very short life span, which is damaging for scholarly research. In 2015, the Dutch Digital Heritage Network (NDE) has started a two-year work program to co-ordinate existing initiatives in order to improve the (long-term) accessibility of the Dutch digital heritage for a wide range of users, anytime, anyplace. The Digital Heritage Network is a partnership established on the initiative of the Ministry of Education, Culture and Science. The members of the NDE are large, national institutions that strive to professionally preserve and manage digital data, e.g. the National Library, The Netherlands Institute for Sound and Vision, the Netherlands Cultural Heritage Agency, the Royal Netherlands Academy of Arts and Sciences, the National Archive of the Netherlands and the DEN Foundation, and a growing number of associations and individuals both within and outside the heritage sector. By means of three work programmes the goals of the Network should be accomplished and improve the visibility, the usability and the sustainability of digital heritage. Each programme contains of a set of projects. Within the sustainability program a project on creating a model for persistent identifiers is taking place. The main goals of the project are (1) raise awareness among cultural heritage institutions on the

  3. Viral Hepatitis Strategic Information to Achieve Elimination by 2030: Key Elements for HIV Program Managers

    Science.gov (United States)

    Low-Beer, Daniel; Bergeri, Isabel; Hess, Sarah; Garcia-Calleja, Jesus Maria; Hayashi, Chika; Mozalevskis, Antons; Rinder Stengaard, Annemarie; Sabin, Keith; Harmanci, Hande; Bulterys, Marc

    2017-01-01

    Evidence documenting the global burden of disease from viral hepatitis was essential for the World Health Assembly to endorse the first Global Health Sector Strategy (GHSS) on viral hepatitis in May 2016. The GHSS on viral hepatitis proposes to eliminate viral hepatitis as a public health threat by 2030. The GHSS on viral hepatitis is in line with targets for HIV infection and tuberculosis as part of the Sustainable Development Goals. As coordination between hepatitis and HIV programs aims to optimize the use of resources, guidance is also needed to align the strategic information components of the 2 programs. The World Health Organization monitoring and evaluation framework for viral hepatitis B and C follows an approach similar to the one of HIV, including components on the following: (1) context (prevalence of infection), (2) input, (3) output and outcome, including the cascade of prevention and treatment, and (4) impact (incidence and mortality). Data systems that are needed to inform this framework include (1) surveillance for acute hepatitis, chronic infections, and sequelae and (2) program data documenting prevention and treatment, which for the latter includes a database of patients. Overall, the commonalities between HIV and hepatitis at the strategic, policy, technical, and implementation levels justify coordination, strategic linkage, or integration, depending on the type of HIV and viral hepatitis epidemics. Strategic information is a critical area of this alignment under the principle of what gets measured gets done. It is facilitated because the monitoring and evaluation frameworks for HIV and viral hepatitis were constructed using a similar approach. However, for areas where elimination of viral hepatitis requires data that cannot be collected through the HIV program, collaborations are needed with immunization, communicable disease control, tuberculosis, and hepatology centers to ensure collection of information for the remaining indicators. PMID

  4. 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.

  5. Sequencing Needs for Viral Diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, S N; Lam, M; Mulakken, N J; Torres, C L; Smith, J R; Slezak, T

    2004-01-26

    We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (''near neighbors'') that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. SARS and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near neighbor sequences are urgently needed. Our results also indicate that double stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.

  6. Viral Infection in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Jovana Cukuranovic

    2012-01-01

    Full Text Available Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

  7. Epigenetic regulation of persistent pain

    Science.gov (United States)

    Bai, Guang; Ren, Ke; Dubner, Ronald

    2014-01-01

    Persistent or chronic pain is tightly associated with various environmental changes and linked to abnormal gene expression within cells processing nociceptive signaling. Epigenetic regulation governs gene expression in response to environmental cues. Recent animal model and clinical studies indicate that epigenetic regulation plays an important role in the development/maintenance of persistent pain and, possibly the transition of acute pain to chronic pain, thus shedding light in a direction for development of new therapeutics for persistent pain. PMID:24948399

  8. Virion-targeted viral inactivation: new therapy against viral infection.

    Science.gov (United States)

    Okui, N; Kitamura, Y; Kobayashi, N; Sakuma, R; Ishikawa, T; Kitamura, T

    2001-01-01

    Acquired immune deficiency syndrome (AIDS) is resistant to all current therapy. Gene therapy is an attractive alternative or additive to current, unsatisfactory AIDS therapy. To develop an antiviral molecule targeting viral integrase (HIV IN), we generated a single-chain antibody, termed scAb, which interacted with human immunodeficiency virus type 1 (HIV-1) IN and inhibited virus replication at the integration step when expressed intracellularly. To reduce infectivity from within the virus particles, we made expression plasmids (pC-scAbE-Vpr, pC-scAbE-CA, and pC-scAbE-WXXF), which expressed the anti-HIV IN scAb fused to the N-terminus of HIV-1-associated accessory protein R (Vpr), capsid protein (CA), and specific binding motif to Vpr (WXXF), respectively. All fusion proteins were tagged with a nine-amino acid peptide derived from influenza virus hemagglutinin (HA) at the C terminus. The fusion molecules, termed scAbE-Vpr, scAbE-CA, and scAbE-WXXF, interacted specifically with HIV IN immobilized on a nitrocellulose membrane. Immunoblot analysis showed that scAbE-Vpr, scAbE-CA, and scAbE-WXXF were incorporated into the virions produced by cotransfection of 293T cells with HIV-1 infectious clone DNA (pLAI) and pC-scAbE-Vpr, pC-scAbE-WXXF. A multinuclear activation galactosidase indicator (MAGI) assay revealed that the virions released from 293T cells cotransfected with pLAI and pC-scAbE-Vpr, pC-scAbE-WXXF had as little 1000-fold of the infectivity of the control wild-type virions, which were produced from the 293T cells transfected with pLAI alone. Furthermore, the virions produced from the 293T cells cotransfected with pLAI and an scAb expression vector (pC-scAb) showed only 1% of the infectivity of the control HIV-1 in a MAGI assay, although scAb was not incorporated into the virions. In either instance, the total quantity of the progeny virions released from the transfected 293T cells and the patterns of the virion proteins were hardly affected by the presence of

  9. 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.

  10. Viral Advertising on Facebook in Vietnam

    OpenAIRE

    Tran, Phuong

    2014-01-01

    The purpose of this thesis is to explore which factors affect the effectiveness of viral advertising on Facebook in Vietnam. The quantitative research method is applied in this research and the sample is Vietnamese Facebook users. After the data analysis stage using SPSS, it became clear that weak ties, perceptual affinity and emotions have an impact on the effectiveness of viral advertising. The results provide a pratical implication of how to make an Ad which can go viral on Facebook. Moreo...

  11. Viral Advertising: Branding Effects from Consumers’ Perspectives

    OpenAIRE

    Jiang, Yueqing

    2012-01-01

    Viral advertising is popular for its high viral transmission results online. Its increased impacts on the social media users have been noticed by the author. At the same time, viewers’ negative attitudes toward traditional advertisements become obvious which can be regarded as the phenomenon of advertisement avoidance. It arouses author’s interests to know how the viral advertising reduces the viewers’ negative emotions and its performances in branding online. This paper is going to look into...

  12. [Workshop on Molecular Epidemiology of Viral Diseases].

    Science.gov (United States)

    Gómez, B; Cabrera, L; Arias, C F

    1997-01-01

    A workshop on viral epidemiology was held on September 29, 1995 at the Medical School of the Universidad Nacional Autónoma de Mexico. The aim of this workshop was to promote interaction among scientists working in viral epidemiology. Eighteen scientists from ten institutions presented their experiences and work. General aspects of the epidemiology of meaningful viral diseases in the country were discussed, and lectures presented on the rota, polio, respiratory syncytial, dengue, papiloma, rabies, VIH and hepatitis viruses.

  13. Viral Subversion of the Nuclear Pore Complex

    Directory of Open Access Journals (Sweden)

    Valerie Le Sage

    2013-08-01

    Full Text Available The nuclear pore complex (NPC acts as a selective barrier between the nucleus and the cytoplasm and is responsible for mediating communication by regulating the transport of RNA and proteins. Numerous viral pathogens have evolved different mechanisms to hijack the NPC in order to regulate trafficking of viral proteins, genomes and even capsids into and out of the nucleus thus promoting virus replication. The present review examines the different strategies and the specific nucleoporins utilized during viral infections as a means of promoting their life cycle and inhibiting host viral defenses.

  14. SUSTAINABLE CHEMISTRY FOR SUSTAINABLE INDUSTRY

    Directory of Open Access Journals (Sweden)

    G. Rizzuto

    2015-01-01

    Full Text Available Foundry Alfe Chem is an industrial reality working in the field of lubrication and chemical auxiliaries for industrial processes, which falls within the framework of the emerging and increasingly important «green chemistry». The goal of the company is to develop products that are more environmentally friendly by using raw materials from renewable sources; specifically, Foundry Alfe Chem has a program of self-sustainability that contemplates, for the foreseeable future, the direct production of renewable raw materials. The company has developed a new dedicated product line, Olitema, whose purpose is to offer highly technological solutions with complete environmental sustainability. In this context, Foundry Alfe CHEM has created a new product which represents a breakthrough in the class of HFC hydraulic fluids: Ecosafe Plus is a biodegradable fire-resistant hydraulic fluid with high engineering and technological performances, high environmental sustainability and the best security guarantees in workplaces. Its formulation is glycols-free, and it allows for easier disposal of the exhausted fluid, compared to a traditional water/ glycol-based HFC hydraulic fluid. For what concern the technological properties, Ecosafe Plus has been tested by accredited laboratories with tribological trials (4 Ball wear test ASTM D 4172, Ball on disc test ASTM 6425, Brugger test DIN 51347, Vickers test ASTM D 2882, with elastomer compatibility test (ASTM D 471 and biodegradability test (OECD 310 F.

  15. Persistent idiopathic facial pain.

    Science.gov (United States)

    Benoliel, Rafael; Gaul, Charly

    2017-06-01

    Background Persistent idiopathic facial pain (PIFP) is a chronic disorder recurring daily for more than two hours per day over more than three months, in the absence of clinical neurological deficit. PIFP is the current terminology for Atypical Facial Pain and is characterized by daily or near daily pain that is initially confined but may subsequently spread. Pain cannot be attributed to any pathological process, although traumatic neuropathic mechanisms are suspected. When present intraorally, PIFP has been termed 'Atypical Odontalgia', and this entity is discussed in a separate article in this special issue. PIFP is often a difficult but important differential diagnosis among chronic facial pain syndromes. Aim To summarize current knowledge on diagnostic criteria, differential diagnosis, pathophysiology and management of PIFP. Methods We present a narrative review reporting current literature and personal experience. Additionally, we discuss and differentiate the common differential diagnoses associated with PIFP including traumatic trigeminal neuropathies, regional myofascial pain, atypical neurovascular pains and atypical trigeminal neuropathic pains. Results and conclusion The underlying pathophysiology in PIFP is still enigmatic, however neuropathic mechanisms may be relevant. PIFP needs interdisciplinary collaboration to rule out and manage secondary causes, psychiatric comorbidities and other facial pain syndromes, particularly trigeminal neuralgia. Burden of disease and psychiatric comorbidity screening is recommended at an early stage of disease, and should be addressed in the management plan. Future research is needed to establish clear diagnostic criteria and treatment strategies based on clinical findings and individual pathophysiology.

  16. 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

  17. Viral diseases of northern ungulates

    Directory of Open Access Journals (Sweden)

    K. Frölich

    2000-03-01

    Full Text Available This paper describes viral diseases reported in northern ungulates and those that are a potential threat to these species. The following diseases are discussed: bovine viral diarrhoea/mucosal disease (BVD/MD, alphaherpesvirus infections, malignant catarrhal fever (MCF, poxvirus infections, parainfluenza type 3 virus infection, Alvsborg disease, foot-and-mouth disease, epizootic haemorrhage disease of deer and bluetongue disease, rabies, respiratory syncytial virus infection, adenovirus infection, hog-cholera, Aujeszky's disease and equine herpesvirus infections. There are no significant differences in antibody prevalence to BVDV among deer in habitats with high, intermediate and low density of cattle. In addition, sequence analysis from the BVDV isolated from roe deer (Capreolus capreolus showed that this strain was unique within BVDV group I. Distinct BVDV strains might circulate in free-ranging roe deer populations in Germany and virus transmission may be independent of domestic livestock. Similar results have been obtained in a serological survey of alpha-herpesviruses in deer in Germany. Malignant catarrhal fever was studied in fallow deer (Cervus dama in Germany: the seroprevalence and positive PCR results detected in sheep originating from the same area as the antibody-positive deer might indicate that sheep are the main reservoir animals. Contagious ecthyma (CE is a common disease in domestic sheep and goats caused by the orf virus. CE has been diagnosed in Rocky Mountain bighorn sheep (Ovis canadensis, mountain goats (Oreamnos americanus, Dall sheep (Ovis dalli, chamois (Rupkapra rupi-capra, muskox {Ovibos moschatus and reindeer (Rangifer tarandus. Most parainfluenza type 3 virus infections are mild or clinically undetectable. Serological surveys in wildlife have been successfully conducted in many species. In 1985, a new disease was identified in Swedish moose (Alces alces, designated as Alvsborg disease. This wasting syndrome probably

  18. A Viral Product Diffusion Model to Forecast the Market Performance of Products

    Directory of Open Access Journals (Sweden)

    Ping Jiang

    2017-01-01

    Full Text Available To investigate the diffusion of products in the market, this paper proposes a viral product diffusion model using an epidemiological approach. This model presents the process of product diffusion through the dynamics of human behaviors. Based on the stability theory of Ordinary Differential Equations, we demonstrate the conditions under which a product in the market persists or dies out eventually. Next, we use Google data to validate the model. Fitting results illustrate that the viral product diffusion model not only depicts the steady growth process of products, but also describes the whole diffusion process during which the products increase at the initial stage and then gradually decrease and sometimes even exhibit multiple peaks. This shows that the viral product diffusion model can be used to forecast the developing tendency of products in the market through early behavior of these products. Moreover, our model also provides useful insights on how to design effective marketing strategies via social contagions.

  19. Sustainable Procurement

    DEFF Research Database (Denmark)

    Telles, Pedro; Ølykke, Grith Skovgaard

    2017-01-01

    and within it how sustainable requirements have increased the level of compliance required, particularly regulatory compliance. Compliance was already present in previous EU public procurement frameworks, but its extent on Directive 2014/24/EU leads the authors to consider the current legal framework...... as subject to substantial regulatory compliance obligations external to the process of procurement. In short, procurement has been transformed in a way to enforce regulatory obligations that are not intrinsic to the process of buying. This leads to the conclusion that questions such as the cost and trade...

  20. Emerging viral diseases of fish and shrimp.

    Science.gov (United States)

    Walker, Peter J; Winton, James R

    2010-01-01

    The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change. © INRA, EDP Sciences, 2010.

  1. An unexpected twist in viral capsid maturation

    Energy Technology Data Exchange (ETDEWEB)

    Gertsman, Ilya; Gan, Lu; Guttman, Miklos; Lee, Kelly; Speir, Jeffrey A.; Duda, Robert L.; Hendrix, Roger W.; Komives, Elizabeth A.; Johnson, John E.; (Pitt); (Scripps); (UCSD)

    2009-04-14

    Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsid structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 {angstrom} resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 {angstrom}. A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and -sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol{sup -1} of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic

  2. Sustainable consumption and marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2016-01-01

    Sustainable development in global food markets is hindered by the discrepancy between positive consumer attitudes towards sustainable development or sustainability and the lack of corresponding sustainable consumption by a majority of consumers. Apparently for many (light user) consumers the

  3. Viral Ancestors of Antiviral Systems

    Science.gov (United States)

    Villarreal, Luis P.

    2011-01-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features. PMID:22069523

  4. Viral Ancestors of Antiviral Systems

    Directory of Open Access Journals (Sweden)

    Luis P. Villarreal

    2011-10-01

    Full Text Available All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  5. Viral ancestors of antiviral systems.

    Science.gov (United States)

    Villarreal, Luis P

    2011-10-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the 'Big Bang' theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  6. Viral Predation and Host Immunity Structure Microbial Communities in a Terrestrial Deep Subsurface, Hydraulically Fractured Shale System

    Science.gov (United States)

    Daly, R. A.; Mouser, P. J.; Trexler, R.; Wrighton, K. C.

    2014-12-01

    Despite a growing appreciation for the ecological role of viruses in marine and gut systems, little is known about their role in the terrestrial deep (> 2000 m) subsurface. We used assembly-based metagenomics to examine the viral component in fluids from hydraulically fractured Marcellus shale gas wells. Here we reconstructed microbial and viral genomes from samples collected 7, 82, and 328 days post fracturing. Viruses accounted for 4.14%, 0.92% and 0.59% of the sample reads that mapped to the assembly. We identified 6 complete, circularized viral genomes and an additional 92 viral contigs > 5 kb with a maximum contig size of 73.6 kb. A BLAST comparison to NCBI viral genomes revealed that 85% of viral contigs had significant hits to the viral order Caudovirales, with 43% of sequences belonging to the family Siphoviridae, 38% to Myoviridae, and 12% to Podoviridae. Enrichment of Caudovirales viruses was supported by a large number of predicted proteins characteristic of tailed viruses including terminases (TerL), tape measure, tail formation, and baseplate related proteins. The viral contigs included evidence of lytic and temperate lifestyles, with the 7 day sample having the greatest number of detected lytic viruses. Notably in this sample, the most abundant virus was lytic and its inferred host, a member of the Vibrionaceae, was not detected at later time points. Analyses of CRISPR sequences (a viral and foreign DNA immune system in bacteria and archaea), linked 18 viral contigs to hosts. CRISPR linkages increased through time and all bacterial and archaeal genomes recovered in the final time point had genes for CRISPR-mediated viral defense. The majority of CRISPR sequences linked phage genomes to several Halanaerobium strains, which are the dominant and persisting members of the community inferred to be responsible for carbon and sulfur cycling in these shales. Network analysis revealed that several viruses were present in the 82 and 328 day samples; this viral

  7. Persistent diffusion on a line

    Science.gov (United States)

    Balakrishnan, V.; Chaturvedi, S.

    1988-02-01

    We consider solutions to the telegraph equation describing persistent diffusion on a line under various initial conditions. The first passage time distribution is evaluated in closed form. Biased persistent diffusion is also considered. A direct derivation of the telegraph equation from the stochastic equation for the displacement is presented in an appendix.

  8. The persistence of depression score

    NARCIS (Netherlands)

    Spijker, J.; de Graaf, R.; Ormel, J.; Nolen, W. A.; Grobbee, D. E.; Burger, H.

    2006-01-01

    Objective: To construct a score that allows prediction of major depressive episode (MDE) persistence in individuals with MDE using determinants of persistence identified in previous research. Method: Data were derived from 250 subjects from the general population with new MDE according to DSM-III-R.

  9. Postpolio syndrome: poliovirus persistence is involved in the pathogenesis.

    Science.gov (United States)

    Julien, J; Leparc-Goffart, I; Lina, B; Fuchs, F; Foray, S; Janatova, I; Aymard, M; Kopecka, H

    1999-06-01

    The pathogenesis of the postpolio syndrome (PPS) remains unclear. In this study we looked for poliovirus (PV) persistence in the CSF of 20 patients with PPS, in a control group including 20 patients with unrelated neurological diseases, and in 7 patients with stable poliomyelitis sequelae. CSF samples and sera were examined using reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of PV or other enterovirus genomes; this assay allows the detection from as little as 1 fg viral RNA. Sequencing of amplified products from 5 patients was performed. PV genomic sequences were detected in the CSF of 11 of 20 patients with PPS and in none of the control group. Sequencing in the 5' untranslated region confirmed the presence of mutated PV sequences. These findings suggest that PPS is related to the persistence of PV in the central nervous system.

  10. Case report of rabies-induced persistent mental symptoms.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Guan, Yangtai

    2015-02-25

    Rabies is a viral infection with a high case fatality rate. Typical symptoms of rabies include hydrophobia, pharynx muscle spasms, and progressive paralysis. Rabies-induced persistent mental disturbances are rare. Here we report a 22-year-old male who was infected with rabies after being attacked by a dog. He did not receive rabies vaccine immediately after the incident and was only provided with non-standard treatment at a local clinic. A week later he became disorientated, paranoid, and aggressive. One month after the attack, rabies antibody was found in his cerebrospinal fluid and a Magnetic Resonance Imaging (MRI) examination of his head revealed abnormal signals in the putamina, caudate nucleus, and insula. His mental symptoms persisted for six years and his daily functioning was severely impaired, but his vital signs were stable without signs of brain stem damage. Six years after the incident, a repeat MRI showed brain atrophy.

  11. Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation

    Directory of Open Access Journals (Sweden)

    Sallie Richard

    2005-02-01

    Full Text Available Abstract Hepatitis C (HCV, hepatitis B (HBV, the human immunodeficiency viruses (HIV, and other viruses that replicate via RNA intermediaries, cause an enormous burden of disease and premature death worldwide. These viruses circulate within infected hosts as vast populations of closely related, but genetically diverse, molecules known as "quasispecies". The mechanism(s by which this extreme genetic and antigenic diversity is stably maintained are unclear, but are fundamental to understanding viral persistence and pathobiology. The persistence of HCV, an RNA virus, is especially problematic and HCV stability, maintained despite rapid genomic mutation, is highly paradoxical. This paper presents the hypothesis, and evidence, that viruses capable of persistent infection autoregulate replication and the likely mechanism mediating autoregulation – Replicative Homeostasis – is described. Replicative homeostasis causes formation of stable, but highly reactive, equilibria that drive quasispecies expansion and generates escape mutation. Replicative homeostasis explains both viral kinetics and the enigma of RNA quasispecies stability and provides a rational, mechanistic basis for all observed viral behaviours and host responses. More importantly, this paradigm has specific therapeutic implication and defines, precisely, new approaches to antiviral therapy. Replicative homeostasis may also modulate cellular gene expression.

  12. Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence.

    Science.gov (United States)

    Sun, Qiming; Tsurimoto, Toshiki; Juillard, Franceline; Li, Lin; Li, Shijun; De León Vázquez, Erika; Chen, She; Kaye, Kenneth

    2014-08-12

    Kaposi's sarcoma-associated herpesvirus (KSHV) latently infects tumor cells and persists as a multiple-copy, extrachromosomal, circular episome. To persist, the viral genome must replicate with each cell cycle. The KSHV latency-associated nuclear antigen (LANA) mediates viral DNA replication and persistence, but little is known regarding the underlying mechanisms. We find that LANA recruits replication factor C (RFC), the DNA polymerase clamp [proliferating cell nuclear antigen (PCNA)] loader, to drive DNA replication efficiently. Mutated LANA lacking RFC interaction was deficient for LANA-mediated DNA replication and episome persistence. RFC depletion had a negative impact on LANA's ability to replicate and maintain viral DNA in cells containing artificial KSHV episomes or in infected cells, leading to loss of virus. LANA substantially increased PCNA loading onto DNA in vitro and recruited RFC and PCNA to KSHV DNA in cells. These findings suggest that PCNA loading is a rate-limiting step in DNA replication that is incompatible with viral survival. LANA enhancement of PCNA loading permits efficient virus replication and persistence, revealing a previously unidentified mechanism for KSHV latency.

  13. (Npro) protein of bovine viral d

    Indian Academy of Sciences (India)

    Prakash

    Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle and sheep, and causes significant respiratory and reproductive disease worldwide. Bovine viral diarrhoea virus type 1 (BVDV-1), BVDV-2 along with the border disease virus (BDV) and classical swine fever virus (CSFV) belong to the genus ...

  14. ANALYTICAL JUSTIFICATION OF INCLUDING THE ANTIVIRAL DRUG INTO TREATMENT SCHEME FOR PATIENTS WITH SUSPECTED VIRAL DISEASE

    Directory of Open Access Journals (Sweden)

    Soloviov S. O

    2016-12-01

    Full Text Available Background: Viruses play a leading role in human pathology development, causing a large number of infectious diseases in acute, persistent or chronic forms. Although the number of deaths caused by viral infections have decreased significantly today, they continue to be a significant factor in reducing of the population overall productivity. Viral diseases cause additional losses in community related to the duration of the course or disease or its chronization, increased use of health care, loss of working hours, premature death etc. Introduction of the new antiviral drugs into medical practice is accompanied by the emergence of questions to assess its effectiveness and including into existing clinical protocols. So the aim of this work is the development of methodology of choosing and justification of optimal treatment strategy for viral diseases that could be included into certain clinical protocols for managing patients with certain viral diseases. Methodology justification: The methodology based on the method of pharmacoeconomic analysis "cost of illness", takes into account the economic burden of viral diseases: direct costs for treating of disease, indirect costs related to the disease and intangible costs. Algorithm of treatment scheme choice depends on the cost of treatment for the patient without viral disease also as for patient with viral disease. It was proposed to use lower limit priori probability (critical prevalence of viral disease as decision rule in the choice of treatment scheme. Results: Examples of the proposed methodology use show that the choice of the optimal therapeutic scheme for patients with suspected viral disease depends on the current prevalence of this disease among patients with similar clinical symptoms of the disease and its cost, depending on the chosen strategy of therapy. The proposed methodology determines the critical level of viral infection prevalence, which comparing to the current prevalence level is

  15. Influence of dendritic cells on viral pathogenicity.

    Science.gov (United States)

    Freer, Giulia; Matteucci, Donatella

    2009-07-01

    Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs) are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses. Certain viruses are able to skew cytokine secretion by DCs inducing and/or downregulating the immune system with the aim of facilitating and prolonging release of progeny. Thus, the interaction of DCs with viruses most often results in the absence of disease or complete recovery when natural functions of DCs prevail, but may lead to chronic illness or death when these functions are outmanoeuvred by viruses in the exploitation of DCs.

  16. Influence of dendritic cells on viral pathogenicity.

    Directory of Open Access Journals (Sweden)

    Giulia Freer

    2009-07-01

    Full Text Available Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses. Certain viruses are able to skew cytokine secretion by DCs inducing and/or downregulating the immune system with the aim of facilitating and prolonging release of progeny. Thus, the interaction of DCs with viruses most often results in the absence of disease or complete recovery when natural functions of DCs prevail, but may lead to chronic illness or death when these functions are outmanoeuvred by viruses in the exploitation of DCs.

  17. Origins and challenges of viral dark matter.

    Science.gov (United States)

    Krishnamurthy, Siddharth R; Wang, David

    2017-07-15

    The accurate classification of viral dark matter - metagenomic sequences that originate from viruses but do not align to any reference virus sequences - is one of the major obstacles in comprehensively defining the virome. Depending on the sample, viral dark matter can make up from anywhere between 40 and 90% of sequences. This review focuses on the specific nature of dark matter as it relates to viral sequences. We identify three factors that contribute to the existence of viral dark matter: the divergence and length of virus sequences, the limitations of alignment based classification, and limited representation of viruses in reference sequence databases. We then discuss current methods that have been developed to at least partially circumvent these limitations and thereby reduce the extent of viral dark matter. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Persistence, resistance, resonance

    Science.gov (United States)

    Tsadka, Maayan

    form of musical consumption and experience. The three pieces draw lines connecting different aspects of persistence, resistance, and resonance.

  19. KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection.

    Directory of Open Access Journals (Sweden)

    Nafisa-Katrin Seich Al Basatena

    2011-10-01

    Full Text Available Killer cell immunoglobulin-like receptors (KIRs influence both innate and adaptive immunity. But while the role of KIRs in NK-mediated innate immunity is well-documented, the impact of KIRs on the T cell response in human disease is not known. Here we test the hypothesis that an individual's KIR genotype affects the efficiency of their HLA class I-mediated antiviral immune response and the outcome of viral infection. We show that, in two unrelated viral infections, hepatitis C virus and human T lymphotropic virus type 1, possession of the KIR2DL2 gene enhanced both protective and detrimental HLA class I-restricted anti-viral immunity. These results reveal a novel role for inhibitory KIRs. We conclude that inhibitory KIRs, in synergy with T cells, are a major determinant of the outcome of persistent viral infection.

  20. Virtual Sustainability

    Directory of Open Access Journals (Sweden)

    William Sims Bainbridge

    2010-09-01

    Full Text Available In four ways, massively multiplayer online role-playing games may serve as tools for advancing sustainability goals, and as laboratories for developing alternatives to current social arrangements that have implications for the natural environment. First, by moving conspicuous consumption and other usually costly status competitions into virtual environments, these virtual worlds might reduce the need for physical resources. Second, they provide training that could prepare individuals to be teleworkers, and develop or demonstrate methods for using information technology to replace much transportation technology, notably in commuting. Third, virtual worlds and online games build international cooperation, even blending national cultures, thereby inching us toward not only the world consciousness needed for international agreements about the environment, but also toward non-spatial government that cuts across archaic nationalisms. Finally, realizing the potential social benefits of this new technology may urge us to reconsider a number of traditional societal institutions.

  1. Sustainability; Sustentabilidade

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter analyses the production chain of ethanol, considering the impacts on the quality of the air, water supplies, soil occupation and biodiversity, and the efforts for the soil preservation. It is pointed out the activities of the production cycle and use of bio ethanol due to great uncertainties as far the environmental impacts is concerning and that will deserve more attention in future evaluations. At same time, the chapter highlights another activities where the present acknowledge is sufficient to assure the control and/or prediction of consequences of the desired intervention on the environment media to accommodate the sugar and ethanol production expansion. The consideration is not conservative but to promote the sustainable development.

  2. Itchy fish and viral dermatopathies: sampling, diagnosis, and management of common viral diseases.

    Science.gov (United States)

    Weber, E P Scott

    2013-09-01

    Viral dermatopathies of fish bear clinical signs similar to those of dermatopathies from other causes. This article offers an overview to approaching dermatologic presentations in fish, with an emphasis on sampling, diagnosis, and management of viral dermatopathies, building on previous publications. It is vital to recognize clinical signs associated with viral dermatopathies because there are currently no treatments available. Avoidance and prevention is the key to controlling viral diseases in fish. Optimizing husbandry practices and providing appropriate quarantine procedures can help prevent viral disease outbreaks in collection and aquaculture stocks. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Digital PCR as a tool to measure HIV persistence.

    Science.gov (United States)

    Rutsaert, Sofie; Bosman, Kobus; Trypsteen, Wim; Nijhuis, Monique; Vandekerckhove, Linos

    2018-01-30

    Although antiretroviral therapy is able to suppress HIV replication in infected patients, the virus persists and rebounds when treatment is stopped. In order to find a cure that can eradicate the latent reservoir, one must be able to quantify the persisting virus. Traditionally, HIV persistence studies have used real-time PCR (qPCR) to measure the viral reservoir represented by HIV DNA and RNA. Most recently, digital PCR is gaining popularity as a novel approach to nucleic acid quantification as it allows for absolute target quantification. Various commercial digital PCR platforms are nowadays available that implement the principle of digital PCR, of which Bio-Rad's QX200 ddPCR is currently the most used platform in HIV research. Quantification of HIV by digital PCR is proving to be a valuable improvement over qPCR as it is argued to have a higher robustness to mismatches between the primers-probe set and heterogeneous HIV, and forfeits the need for a standard curve, both of which are known to complicate reliable quantification. However, currently available digital PCR platforms occasionally struggle with unexplained false-positive partitions, and reliable segregation between positive and negative droplets remains disputed. Future developments and advancements of the digital PCR technology are promising to aid in the accurate quantification and characterization of the persistent HIV reservoir.

  4. Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART

    Science.gov (United States)

    Denton, Paul W.; Long, Julie M.; Wietgrefe, Stephen W.; Sykes, Craig; Spagnuolo, Rae Ann; Snyder, Olivia D.; Perkey, Katherine; Archin, Nancie M.; Choudhary, Shailesh K.; Yang, Kuo; Hudgens, Michael G.; Pastan, Ira; Haase, Ashley T.; Kashuba, Angela D.; Berger, Edward A.; Margolis, David M.; Garcia, J. Victor

    2014-01-01

    Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA+ cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies. PMID:24415939

  5. Sustainability Science Needs Sustainable Data!

    Science.gov (United States)

    Downs, R. R.; Chen, R. S.

    2013-12-01

    Sustainability science (SS) is an 'emerging field of research dealing with the interactions between natural and social systems, and with how those interactions affect the challenge of sustainability: meeting the needs of present and future generations while substantially reducing poverty and conserving the planet's life support systems' (Kates, 2011; Clark, 2007). Bettencourt & Kaur (2011) identified more than 20,000 scientific papers published on SS topics since the 1980s with more than 35,000 distinct authors. They estimated that the field is currently growing exponentially, with the number of authors doubling approximately every 8 years. These scholars are undoubtedly using and generating a vast quantity and variety of data and information for both SS research and applications. Unfortunately we know little about what data the SS community is actually using, and whether or not the data that SS scholars generate are being preserved for future use. Moreover, since much SS research is conducted by cross-disciplinary, multi-institutional teams, often scattered around the world, there could well be increased risks of data loss, reduced data quality, inadequate documentation, and poor long-term access and usability. Capabilities and processes therefore need to be established today to support continual, reliable, and efficient preservation of and access to SS data in the future, especially so that they can be reused in conjunction with future data and for new studies not conceived in the original data collection activities. Today's long-term data stewardship challenges include establishing sustainable data governance to facilitate continuing management, selecting data to ensure that limited resources are focused on high priority SS data holdings, securing sufficient rights to allow unforeseen uses, and preparing data to enable use by future communities whose specific research and information needs are not yet known. Adopting sustainable models for archival

  6. Energy landscapes and persistent minima

    Energy Technology Data Exchange (ETDEWEB)

    Carr, Joanne M.; Wales, David J., E-mail: dw34@cam.ac.uk [University Chemical Laboratories, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Mazauric, Dorian; Cazals, Frédéric, E-mail: frederic.cazals@inria.fr [Inria Sophia Antipolis Méditerranée, 2004 route des Lucioles, F-06902 Sophia Antipolis (France)

    2016-02-07

    We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests.

  7. Energy landscapes and persistent minima

    Science.gov (United States)

    Carr, Joanne M.; Mazauric, Dorian; Cazals, Frédéric; Wales, David J.

    2016-02-01

    We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests.

  8. Dynamics of viral spread in bluetongue virus infected calves.

    Science.gov (United States)

    Barratt-Boyes, S M; MacLachlan, N J

    1994-06-01

    The kinetics of viremia and sites of viral replication in bluetongue virus (BTV) infected calves were characterized by virus isolation, serology and immunofluorescence staining procedures. In addition, the role of the regional lymph node and lymphatics draining inoculated skin in the pathogenesis of BTV infection was determined by analyzing efferent lymph collected from indwelling cannulas. Viremia persisted for 35 to 42 days after inoculation (DAI) and virus co-circulated with neutralizing antibodies for 23 to 26 days. Virus was first isolated from peripheral blood mononuclear (PBM) cells at 3 DAI, after stimulation of PBM cells with interleukin 2 and mitogen. BTV was frequently isolated from erythrocytes, platelets and stimulated PBM cells but never from granulocytes and rarely from plasma during viremia. Virus was consistently isolated from erythrocytes late in the course of viremia. Interruption of efferent lymph flow by cannulation delayed the onset of viremia to 7 DAI. BTV was infrequently isolated from lymph cells, and few fluorescence positive cells were observed after lymph and PBM cells were labelled with a BTV-specific monoclonal antibody. Virus was isolated from spleen by 4 DAI and most tissues by 6 DAI, whereas virus was isolated from bone marrow only at 10 DAI. Virus was not isolated from any tissue after termination of viremia. It is concluded that primary viral replication occurred in the local lymph node and BTV then was transported in low titer to secondary sites of replication via infected lymph and PBM cells. We speculate that virus replication in spleen resulted in release of virus into the circulation and non-selective infection of blood cells which disseminated BTV to other tissues. Virus association with erythrocytes likely was responsible for prolonged viremia, although infected erythrocytes eventually were cleared from the circulation and persistent BTV infection of calves did not occur.

  9. A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model.

    Directory of Open Access Journals (Sweden)

    Iart Luca Shytaj

    Full Text Available Stably suppressed viremia during ART is essential for establishing reliable simian models for HIV/AIDS. We tested the efficacy of a multidrug ART (highly intensified ART in a wide range of viremic conditions (10³-10⁷ viral RNA copies/mL in SIVmac251-infected rhesus macaques, and its impact on the viral reservoir. Eleven macaques in the pre-AIDS stage of the disease were treated with a multidrug combination (highly intensified ART consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir, an integrase inhibitor (raltegravir, a protease inhibitor (ritonavir-boosted darunavir and the CCR5 blocker maraviroc. All animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 RNA copies/mL after starting highly intensified ART. By increasing the sensitivity of the assay to 3 RNA copies/mL, viral load was still below the limit of detection in all subjects tested. Importantly, viral DNA resulted below the assay detection limit (<2 copies of DNA/5*10⁵ cells in PBMCs and rectal biopsies of all animals at the end of the follow-up, and in lymph node biopsies from the majority of the study subjects. Moreover, highly intensified ART decreased central/transitional memory, effector memory and activated (HLA-DR⁺ effector memory CD4⁺ T-cells in vivo, in line with the role of these subsets as the main cell subpopulations harbouring the virus. Finally, treatment with highly intensified ART at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle, thus leading to a persistent suppression of viremia in the absence of ART. In conclusion, we show, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing

  10. Evaluation of reproductive protection against bovine viral diarrhea virus and bovine herpesvirus-1 afforded by annual revaccination with modified-live viral or combination modified-live/killed viral vaccines after primary vaccination with modified-live viral vaccine.

    Science.gov (United States)

    Walz, Paul H; Givens, M Daniel; Rodning, Soren P; Riddell, Kay P; Brodersen, Bruce W; Scruggs, Daniel; Short, Thomas; Grotelueschen, Dale

    2017-02-15

    The objective of this study was to compare reproductive protection in cattle against bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BoHV-1) provided by annual revaccination with multivalent modified-live viral (MLV) vaccine or multivalent combination viral (CV) vaccine containing temperature-sensitive modified-live BoHV-1 and killed BVDV when MLV vaccines were given pre-breeding to nulliparous heifers. Seventy-five beef heifers were allocated into treatment groups A (n=30; two MLV doses pre-breeding, annual revaccination with MLV vaccine), B (n=30; two MLV doses pre-breeding, annual revaccination with CV vaccine) and C (n=15; saline in lieu of vaccine). Heifers were administered treatments on days 0 (weaning), 183 (pre-breeding), 366 (first gestation), and 738 (second gestation). After first calving, primiparous cows were bred, with pregnancy assessment on day 715. At that time, 24 group A heifers (23 pregnancies), 23 group B heifers (22 pregnancies), and 15 group C heifers (15 pregnancies) were commingled with six persistently infected (PI) cattle for 16days. Ninety-nine days after PI removal, cows were intravenously inoculated with BoHV-1. All fetuses and live offspring were assessed for BVDV and BoHV-1. Abortions occurred in 3/23 group A cows, 1/22 group B cows, and 11/15 group C cows. Fetal infection with BVDV or BoHV-1 occurred in 4/23 group A offspring, 0/22 group B offspring, and 15/15 group C offspring. This research demonstrates efficacy of administering two pre-breeding doses of MLV vaccine with annual revaccination using CV vaccine to prevent fetal loss due to exposure to BVDV and BoHV-1. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Production and titering of recombinant adeno-associated viral vectors.

    Science.gov (United States)

    McClure, Christina; Cole, Katy L H; Wulff, Peer; Klugmann, Matthias; Murray, Andrew J

    2011-11-27

    In recent years recombinant adeno-associated viral vectors (AAV) have become increasingly valuable for in vivo studies in animals, and are also currently being tested in human clinical trials. Wild-type AAV is a non-pathogenic member of the parvoviridae family and inherently replication-deficient. The broad transduction profile, low immune response as well as the strong and persistent transgene expression achieved with these vectors has made them a popular and versatile tool for in vitro and in vivo gene delivery. rAAVs can be easily and cheaply produced in the laboratory and, based on their favourable safety profile, are generally given a low safety classification. Here, we describe a method for the production and titering of chimeric rAAVs containing the capsid proteins of both AAV1 and AAV2. The use of these so-called chimeric vectors combines the benefits of both parental serotypes such as high titres stocks (AAV1) and purification by affinity chromatography (AAV2). These AAV serotypes are the best studied of all AAV serotypes, and individually have a broad infectivity pattern. The chimeric vectors described here should have the infectious properties of AAV1 and AAV2 and can thus be expected to infect a large range of tissues, including neurons, skeletal muscle, pancreas, kidney among others. The method described here uses heparin column purification, a method believed to give a higher viral titer and cleaner viral preparation than other purification methods, such as centrifugation through a caesium chloride gradient. Additionally, we describe how these vectors can be quickly and easily titered to give accurate reading of the number of infectious particles produced.

  12. Cortical representation of persistent visual stimuli.

    Science.gov (United States)

    Gerber, Edden M; Golan, Tal; Knight, Robert T; Deouell, Leon Y

    2017-08-12

    Research into visual neural activity has focused almost exclusively on onset- or change-driven responses and little is known about how information is encoded in the brain during sustained periods of visual perception. We used intracranial recordings in humans to determine the degree to which the presence of a visual stimulus is persistently encoded by neural activity. The correspondence between stimulus duration and neural response duration was strongest in early visual cortex and gradually diminished along the visual hierarchy, such that is was weakest in inferior-temporal category-selective regions. A similar posterior-anterior gradient was found within inferior temporal face-selective regions, with posterior but not anterior sites showing persistent face-selective activity. The results suggest that regions that appear uniform in terms of their category selectivity are dissociated by how they temporally represent a stimulus in support of ongoing visual perception, and delineate a large-scale organizing principle of the ventral visual stream. Copyright © 2017. Published by Elsevier Inc.

  13. Picobirnavirus causes persistent infection in pigs.

    Science.gov (United States)

    Martínez, Laura C; Masachessi, Gisela; Carruyo, Gabriela; Ferreyra, Leonardo J; Barril, Patricia A; Isa, María B; Giordano, Miguel O; Ludert, Juan E; Nates, Silvia V

    2010-10-01

    A study aimed to further understand the biology of porcine picobirnaviruses (PBV) was conducted between November 2003 and January 2008, on a farm located in the outskirts of Córdoba City, Argentina. PBV prevalence was examined by polyacrylamide gel electrophoresis and silver staining (PAGE S/S) on a total of 265 samples collected from pigs divided into four groups, according to age and physiological status. PBV detection rate was highest in the group of sows sampled within the lactogenic period (38.02%; p or =50 weeks) male pigs (0%). In addition, 103 samples collected in 3 follow-up studies were analyzed by PAGE S/S and reverse transcription followed by PCR (RT-PCR). Two of these studies followed female pigs from weaning up to slaughter and a third one from weaning up to 4 pregnancy periods. The results provide evidence that PBV establishes a persistent infection in the host with periods of silence intermingled with periods of low and high viral excretion. High PBV excretion levels were detected by PAGE S/S and were conditioned by age (primary infection) and host physiological status. Low PBV excretion levels were detected by RT-PCR throughout the entire study period. Sequence analysis of selected amplicons indicated that the virus excreted through the follow-up study was the same. These results suggest that porcine PBV is maintained in nature by transmission from infected asymptomatic individuals to susceptible ones. Copyright 2010 Elsevier B.V. All rights reserved.

  14. [MOLECULAR ASPECTS OF BRUCELLA PERSISTENCE].

    Science.gov (United States)

    Kulakov Yu K

    2016-01-01

    Brucellosis is a dangerous zoonotic disease of animals and humans caused by bacteria of the genus Brucella, which are able to survive, multiply, and persist in host cells. The review is devoted to the Brucella species persistence connected to the molecular mechanisms of escape from innate and adaptive immunity of the host and active interaction of effector proteins of the type IV secretion system with the host's signaling pathways. Understanding of the molecular mechanisms used by Brucella for the intracellular persistence in the host organism can allow us to develop new and effective means for the prevention and treatment of chronic brucellosis infection.

  15. Rapid host immune response and viral dynamics in herpes simplex virus-2 infection

    Science.gov (United States)

    Schiffer, Joshua T; Corey, Lawrence

    2014-01-01

    Herpes Simplex Virus-2 (HSV-2) is episodically shed throughout the human genital tract. While high viral load correlates with development of genital ulcers, shedding also commonly occurs even when ulcers are not present, allowing for silent transmission during coitus and contributing to high seroprevalence of HSV-2 worldwide. Frequent viral reactivation occurs despite diverse and complementary host and viral mechanisms within ganglionic tissue that predispose towards latency, suggesting that viral replication may be constantly occurring in a small minority of neurons within the ganglia. Within genital mucosa, the in vivo expansion and clearance rates of HSV-2 are extremely rapid. Resident dendritic cells and memory HSV-specific T cells persist at prior sites of genital tract reactivation, and in conjunction with prompt innate recognition of infected cells, lead to rapid containment of infected cells. Shedding episodes vary greatly in duration and severity within a single person over time: this heterogeneity appears best explained by variation in the densities of host immunity across the genital tract. The fact that immune responses usually control viral replication in genital skin prior to development of lesions provides optimism that enhancing such responses could lead to effective vaccines and immunotherapies. PMID:23467247

  16. A multilevel evolutionary framework for sustainability analysis

    Directory of Open Access Journals (Sweden)

    Timothy M. Waring

    2015-06-01

    Full Text Available Sustainability theory can help achieve desirable social-ecological states by generalizing lessons across contexts and improving the design of sustainability interventions. To accomplish these goals, we argue that theory in sustainability science must (1 explain the emergence and persistence of social-ecological states, (2 account for endogenous cultural change, (3 incorporate cooperation dynamics, and (4 address the complexities of multilevel social-ecological interactions. We suggest that cultural evolutionary theory broadly, and cultural multilevel selection in particular, can improve on these fronts. We outline a multilevel evolutionary framework for describing social-ecological change and detail how multilevel cooperative dynamics can determine outcomes in environmental dilemmas. We show how this framework complements existing sustainability frameworks with a description of the emergence and persistence of sustainable institutions and behavior, a means to generalize causal patterns across social-ecological contexts, and a heuristic for designing and evaluating effective sustainability interventions. We support these assertions with case examples from developed and developing countries in which we track cooperative change at multiple levels of social organization as they impact social-ecological outcomes. Finally, we make suggestions for further theoretical development, empirical testing, and application.

  17. 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.

  18. Assembly of viral genomes from metagenomes

    Directory of Open Access Journals (Sweden)

    Saskia L Smits

    2014-12-01

    Full Text Available Viral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow rapid phylogenetic characterization of these new viruses. Often, however, complete viral genomes are not recovered, but rather several distinct contigs derived from a single entity, some of which have no sequence homology to any known proteins. De novo assembly of single viruses from a metagenome is challenging, not only because of the lack of a reference genome, but also because of intrapopulation variation and uneven or insufficient coverage. Here we explored different assembly algorithms, remote homology searches, genome-specific sequence motifs, k-mer frequency ranking, and coverage profile binning to detect and obtain viral target genomes from metagenomes. All methods were tested on 454-generated sequencing datasets containing three recently described RNA viruses with a relatively large genome which were divergent to previously known viruses from the viral families Rhabdoviridae and Coronaviridae. Depending on specific characteristics of the target virus and the metagenomic community, different assembly and in silico gap closure strategies were successful in obtaining near complete viral genomes.

  19. Persistent forecasting of disruptive technologies

    National Research Council Canada - National Science Library

    Committee on Forecasting Future Disruptive Technologies; National Research Council

    ...) and the Defense Intelligence Agency (DIA) tasked the Committee for Forecasting Future Disruptive Technologies with providing guidance and insight on how to build a persistent forecasting system to predict, analyze, and reduce the impact...

  20. Persistent postoperative hiccups: a review

    DEFF Research Database (Denmark)

    Hansen, B J; Rosenberg, J

    1993-01-01

    The pathogenesis of persistent postoperative hiccups is not known. Hiccups can present as a symptom of a subphrenic abscess of gastric distention, and metabolic alterations may also cause hiccups. The hiccups may develop because of increased activity in neural reflex pathways not yet fully defined....... Numerous treatment modalities have been tried but with questionable success. Valproate has proven effective in two trials investigating persistent non-surgical hiccups. The simple application of a nasogastric tube may successfully treat the hiccups, possibly because of an alteration of the activity...... in the reflex neural pathways involved. The available literature on the treatment of persistent hiccups is reviewed, and a treatment protocol for persistent postoperative hiccups is provided....

  1. Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.

    Directory of Open Access Journals (Sweden)

    Xiaofei E

    2009-10-01

    Full Text Available Gamma-herpesviruses (gammaHVs have developed an interaction with their hosts wherein they establish a life-long persistent infection and are associated with the onset of various malignancies. One critical virulence factor involved in the persistency of murine gamma-herpesvirus 68 (gammaHV68 is the viral homolog of the Bcl-2 protein (vBcl-2, which has been implicated to counteract both host apoptotic responses and autophagy pathway. However, the relative significance of the two activities of vBcl-2 in viral persistent infection has yet to be elucidated. Here, by characterizing a series of loss-of-function mutants of vBcl-2, we have distinguished the vBcl-2-mediated antagonism of autophagy from the vBcl-2-mediated inhibition of apoptosis in vitro and in vivo. A mutant gammaHV68 virus lacking the anti-autophagic activity of vBcl-2 demonstrates an impaired ability to maintain chronic infections in mice, whereas a mutant virus lacking the anti-apoptotic activity of vBcl-2 establishes chronic infections as efficiently as the wild-type virus but displays a compromised ability for ex vivo reactivation. Thus, the vBcl-2-mediated antagonism of host autophagy constitutes a novel mechanism by which gammaHVs confer persistent infections, further underscoring the importance of autophagy as a critical host determinant in the in vivo latency of gamma-herpesviruses.

  2. Inflation Persistence and Relative Contracting

    OpenAIRE

    John C. Driscoll; Steinar Holden

    2003-01-01

    Macroeconomists have for some time been aware that the New Keynesian Phillips curve, though highly popular in the literature, cannot explain the persistence observed in actual inflation. We argue that one of the more prominent alternative formulations, the Fuhrer and Moore (1995) relative contracting model, is highly problematic. Fuhrer and Moore's 1995 formulation generates inflation persistence, but this is a consequence of their assuming that workers care about the past real wages of other...

  3. Teriparatide Induced Delayed Persistent Hypercalcemia

    Directory of Open Access Journals (Sweden)

    Nirosshan Thiruchelvam

    2014-01-01

    Full Text Available Teriparatide, a recombinant PTH, is an anabolic treatment for osteoporosis that increases bone density. Transient hypercalcemia is a reported side effect of teriparatide that is seen few hours following administration of teriparatide and resolves usually within 16 hours of drug administration. Persistent hypercalcemia, although not observed in clinical trials, is rarely reported. The current case describes a rare complication of teriparatide induced delayed persistent hypercalcemia.

  4. Sustainable Scientists

    Energy Technology Data Exchange (ETDEWEB)

    Mills, Evan

    2008-12-31

    Scientists are front and center in quantifying and solving environmental problems. Yet, as a spate of recent news articles in scientific journals point out, much can be done to enhance sustainability within the scientific enterprise itself, particularly by trimming the energy use associated with research facilities and the equipment therein (i,ii,iii, iv). Sponsors of research unwittingly spend on the order of $10 billion each year on energy in the U.S. alone, and the underlying inefficiencies drain funds from the research enterprise while causing 80 MT CO2-equivalent greenhouse-gas emissions (see Box). These are significant sums considering the opportunity costs in terms of the amount of additional research that could be funded and emissions that could be reduced if the underlying energy was used more efficiently. By following commercially proven best practices in facility design and operation, scientists--and the sponsors of science--can cost-effectively halve these costs, while doing their part to put society on alow-carbon diet.

  5. 20 Years of Persistent Identifiers – Which Systems are Here to Stay?

    Directory of Open Access Journals (Sweden)

    Jens Klump

    2017-03-01

    Full Text Available Web-based persistent identifiers have been around for more than 20 years, a period long enough for us to start observing patterns of success and failure. Persistent identifiers were invented to address challenges arising from the distributed and disorganised nature of the internet, which often resulted in URLs to internet endpoints becoming invalid. Over the years several different persistent identifier systems have been applied to the identification of research data, not all with the same level of success in terms of uptake and sustainability. We investigate the uptake of persistent identifier systems and discuss the factors that might determine the stability and longevity of these systems. Persistent identifiers have become essential elements of global research data infrastructures. Understanding the factors that influence the stability and longevity of persistent identifier systems will help us guide the future development of this important element of research data infrastructures and will make it easier to adapt to future technological and organisational changes.

  6. Vaccines in the Prevention of Viral Pneumonia.

    Science.gov (United States)

    Fraser, Clementine S; Jha, Akhilesh; Openshaw, Peter J M

    2017-03-01

    Pneumonia is of great global public health importance. Viral infections play both direct and indirect parts in its cause across the globe. Influenza is a leading cause of viral pneumonia in both children and adults, and respiratory syncytial virus is increasingly recognized as causing disease at both extremes of age. Vaccination offers the best prospect for prevention but current influenza vaccines do not provide universal and durable protection, and require yearly reformulation. In the future, it is hoped that influenza vaccines will give better and universal protection, and that new vaccines can be found for other causes of viral pneumonia. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Sustainable agriculture - selected papers

    OpenAIRE

    Krasowicz, Stanisław; Wrzaszcz, Wioletta; Zegar, Jozef St.

    2007-01-01

    The concept of research on socially sustainable agriculture. Features of sustainable agriculture. Sustainability of private farms in the light of selected criteria. Subsistence agricultural holdings and the sustainable development of agriculture. Sustainable farms in the light of the FADN data. Description of organic holdings in Poland.

  8. Evaluating viral marketing: isolating the key criteria in insurance industry

    National Research Council Canada - National Science Library

    Maria Gooyandeh Hagh

    2015-01-01

    This paper presents an empirical investigation to determine the key criteria that viral marketing practitioners believe should be implemented to measure about the success of viral marketing campaigns...

  9. EXPERIMENTAL LIPOSOMAL VIRAL VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Romanova OA

    2016-12-01

    Full Text Available Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay;b lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase.Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France, "Inflexal V" (Biotech Ltd. Berne, Switzerland and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane. Liposomes 2.2 - the adjuvant

  10. Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery

    NARCIS (Netherlands)

    Engsig, Frederik N.; Zangerle, Robert; Katsarou, Olga; Dabis, Francois; Reiss, Peter; Gill, John; Porter, Kholoud; Sabin, Caroline; Riordan, Andrew; Fätkenheuer, Gerd; Gutiérrez, Félix; Raffi, Francois; Kirk, Ole; Mary-Krause, Murielle; Stephan, Christoph; de Olalla, Patricia Garcia; Guest, Jodie; Samji, Hasina; Castagna, Antonella; D'Arminio Monforte, Antonella; Skaletz-Rorowski, Adriane; Ramos, Jose; Lapadula, Giuseppe; Mussini, Cristina; Force, Lluís; Meyer, Laurence; Lampe, Fiona; Boufassa, Faroudy; Bucher, Heiner C.; de Wit, Stéphane; Burkholder, Greer A.; Teira, Ramon; Justice, Amy C.; Sterling, Tim R.; M Crane, Heidi; Gerstoft, Jan; Grarup, Jesper; May, Margaret; Chêne, Geneviève; Ingle, Suzanne M.; Sterne, Jonathan; Obel, Niels; Burkholder, Greer; Justice, Amy; R Sterling, Tim; Crane, Heidi M.; Boulle, Andrew; Brodt, Hans-Reinhard; Casabona, Jordi; Cavassini, Matthias; Costagliola, Dominique; Dabis, François; del Amo, Julia; van Sighem, Ard; Hans-Ulrich Haerry, David; Hogg, Robert; Mocroft, Amanda; Kitahata, Mari; Saag, Michael; Williams, Matthew; Ingle, Suzanne; Touloumi, Giota; Warszawski, Josiane; Krause, Murielle Mary; Ghosn, Jade; Leport, Catherine; Wit, Ferdinand; Prins, Maria; Gibb, Diana; Thorne, Claire; Pérez-Hoyos, Santiago; Hamouda, Osamah; Gussenheimer-Bartmeyer, Barbara; Noguera-Julian, Antoni; Antinori, Andrea; Brockmeyer, Norbert; Ramos, José; Battegay, Manuel; Rauch, Andri; Tookey, Pat; Miró, Jose M.; de Wit, Stephane; Goetghebuer, Tessa; Torti, Carlo; Garrido, Myriam; Judd, Ali; Conejo, Pablo Rojo; Haerry, David; Weller, Ian; D'Arminio-Monforte, Antonella; Colin, Céline; Schwimmer, Christine; Termote, Monique; Kjaer, Jesper; Campbell, Maria; Raben, Dorthe; Bohlius, Julia; Bouteloup, Vincent; Bucher, Heiner; Cozzi-Lepri, Alessandro; Dorrucci, Maria; Egger, Matthias; Engsig, Frederik; Furrer, Hansjakob; Lambotte, Olivier; Lewden, Charlotte; Lodi, Sara; Lodwick, Rebbeca; Matheron, Sophie; Miro, Jose; Monge, Susana; Nakagawa, Fumiyo; Paredes, Roger; Phillips, Andrew; Puoti, Massimo; Reekie, Joanne; Scherrer, Alexandra; Smit, Colette; Thiebaut, Rodolphe; Wittkop, Linda

    2014-01-01

    Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained

  11. Sustainable NREL - Site Sustainability Plan FY 2015

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-01-01

    NREL's Site Sustainability Plan FY 2015 reports on sustainability plans for the lab for the year 2015 based on Executive Order Goals and provides the status on planned actions cited in the FY 2014 report.

  12. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

    Directory of Open Access Journals (Sweden)

    Asma Ahmed

    2015-12-01

    Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  13. Novel oncolytic viral therapies in patients with thoracic malignancies

    Directory of Open Access Journals (Sweden)

    Ahmad Z

    2016-12-01

    Full Text Available Zeeshan Ahmad, Robert A Kratzke Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA Abstract: Oncolytic virotherapy is the use of replication-competent viruses to treat malignancies. The potential of oncolytic virotherapy as an approach to cancer therapy is based on historical evidence that certain viral infections can cause spontaneous remission of both hematologic and solid tumor malignancies. Oncolytic virotherapy may eliminate cancer cells through either direct oncolysis of infected tumor cells or indirect immune-mediated oncolysis of uninfected tumor cells. Recent advances in oncolytic virotherapy include the development of a wide variety of genetically attenuated RNA viruses with precise cellular tropism and the identification of cell-surface receptors that facilitate viral transfer to the tissue of interest. Current research is also focused on targeting metastatic disease by sustaining the release of progeny viruses from infected tumor cells and understanding indirect tumor cell killing through immune-mediated mechanisms of virotherapy. The purpose of this review is to critically evaluate recent evidence on the clinical development of tissue-specific viruses capable of targeting tumor cells and eliciting secondary immune responses in lung cancers and mesothelioma. Keywords: lung cancer, mesothelioma, VSV, adenovirus, measles

  14. Viral fitness: definitions, measurement, and current insights

    Science.gov (United States)

    Wargo, Andrew R.; Kurath, Gael

    2012-01-01

    Viral fitness is an active area of research, with recent work involving an expanded number of human, non-human vertebrate, invertebrate, plant, and bacterial viruses. Many publications deal with RNA viruses associated with major disease emergence events, such as HIV-1, influenza virus, and Dengue virus. Study topics include drug resistance, immune escape, viral emergence, host jumps, mutation effects, quasispecies diversity, and mathematical models of viral fitness. Important recent trends include increasing use of in vivo systems to assess vertebrate virus fitness, and a broadening of research beyond replicative fitness to also investigate transmission fitness and epidemiologic fitness. This is essential for a more integrated understanding of overall viral fitness, with implications for disease management in the future.

  15. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases but...

  16. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2016. In this Table, provisional* cases of selected†notifiable diseases (≥1,000 cases reported during the preceding...

  17. NNDSS - Table II. Hepatitis (viral, acute) C

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) C - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  18. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  19. CHOLESTASIS IN ACUTE AND CHRONIC VIRAL HEPATITIS

    Directory of Open Access Journals (Sweden)

    V. F. Uchaikin

    2014-01-01

    Full Text Available We observed 43 patients with cholestasis (21 — with acute viral hepatitis A and B and 22 — with chronic viral hepatitis B and C. Etiological diagnosis was based on the identification of specific markers of the spectrum. These 43 patients in addition to basic therapy ursodeoxycholic acid as a drug Ursosan of company «PRO.MED.CS Praha a.s.» (CzechRepublic. The control group consisted of 17 patients with acute viral hepatitis. Clinical signs are jaundice and itching of the skin, abdominal pain, significant hepatomegaly. Serum bilirubin level rises due to the conjugated fraction, alkaline phosphatase, gamma-glutamyltranspeptidase. When ultrasound revealed dilated bile ducts in the liver parenchyma, reactive edema of the gallbladder wall, signs gipomotornoy dyskinesia. Appointment ursosan in acute and chronic viral hepatitis occurring with cholestasis leads to the clinical and biochemical effects, and has a beneficial effect on the state of the liver and gall bladder.

  20. Characterization of the viral O-glycopeptidome

    DEFF Research Database (Denmark)

    Cló, Emiliano; Kracun, Stjepan K; Nudelman, Aaron S

    2012-01-01

    also lead to aberrant glycosylation that may elicit immunity. Our knowledge of immunity to aberrant viral glycans and glycoproteins is limited, potentially due to technical limitations in identifying immunogenic glycans and glycopeptide epitopes. This work describes three different complementary...

  1. [Pediatrics. New treatment options for viral bronchiolitis].

    Science.gov (United States)

    Rochat, I; Hafen, G

    2013-01-16

    The combination of nebulized epinephrine and high dose dexamethasone, or nebulized hypertonic saline, are promising new therapeutic strategies for viral bronchiolitis in the young infant. However, further research is needed before a general recommendation can be given.

  2. Drug Use and Viral Infections (HIV, Hepatitis)

    Science.gov (United States)

    ... Viral) HIV/AIDS Mental Health Military Opioid Overdose Reversal with Naloxone (Narcan, Evzio) Pain Prevention Recovery Substance ... as sharing drug-use equipment and having unprotected sex, which can lead to these infections. Getting treatment. ...

  3. transfusion transmissible viral infections among potential blood

    African Journals Online (AJOL)

    boaz

    Key words: Transfusion Transmissible Infections, HIV, Hepatitis B, Hepatitis C, Blood Donors,. University College Hospital (UCH), ELISA. INTRODUCTION. The most common diseases transmitted in blood transfusions are viral infections. Transfusion- transmissible infectious agents such as human immunodeficiency virus ...

  4. Viruses, anti-viral therapy, and viral vaccines in children with immune thrombocytopenia.

    Science.gov (United States)

    Elalfy, Mohsen S; Nugent, Diane

    2016-04-01

    Immune thrombocytopenia (ITP) might be preceded by silent or overt viral infections. Similarly, anti-viral drugs and viral vaccines could also trigger ITP and might play a central role in its pathogenesis. The seasonal nature of childhood ITP suggests that viral infections might initiate immune responses that increase the predisposition and occurrence of ITP. Active cytomegalovirus or Epstein-Barr virus should be considered in differential diagnosis when thrombocytopenia is associated with lymphadenopathy, especially with splenomegaly. This review will focus on the specific association of ITP in association with viral disease and vaccinations, and will discuss the effectiveness of current therapies in light of our current understanding of viral-associated ITP. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Viral Management as a New Type of Enterprise Management in Coal Industry

    Directory of Open Access Journals (Sweden)

    Garafonova Olga

    2017-01-01

    Full Text Available The article considers the evolution of the concept of “management”. The Internet analysis of the concept of “viral management” was conducted, the results of which testify to the positive trend, the growing interest in scientific circles, the relevance of the chosen direction for further research and the increasing popularity of the viral management among business leaders. The indices of coal and brown coal extraction in Ukraine and Russia for 2010-2016 are analyzed. Among the problems that exist in the coal industry are the following: mine assets have a high degree of deterioration; the equipment is rather obsolete and does not correspond to the world level; among the existing face equipment, the specific weight of longwall mining equipment, road headers, loading machines, and belt conveyors of the new generation is only several percent. Five steps of introduction of the virus management at the enterprise are identified: opening, development, participation, diffusion, sustainability. The principles of introduction of the viral management in the enterprises of the coal industry are offered. It is established that the main idea of the viral management is to “infect” the organization and, mainly, employees with one or another “virus” in the form of a common idea or goal. It is indicated that the viral management assumes a certain automaticity of changes, internal “obsession” with this or other innovation, involvement of an informal personal factor.

  6. Viral Management as a New Type of Enterprise Management in Coal Industry

    Science.gov (United States)

    Garafonova, Olga; Grigashkina, Svetlana; Zhosan, Anna

    2017-11-01

    The article considers the evolution of the concept of "management". The Internet analysis of the concept of "viral management" was conducted, the results of which testify to the positive trend, the growing interest in scientific circles, the relevance of the chosen direction for further research and the increasing popularity of the viral management among business leaders. The indices of coal and brown coal extraction in Ukraine and Russia for 2010-2016 are analyzed. Among the problems that exist in the coal industry are the following: mine assets have a high degree of deterioration; the equipment is rather obsolete and does not correspond to the world level; among the existing face equipment, the specific weight of longwall mining equipment, road headers, loading machines, and belt conveyors of the new generation is only several percent. Five steps of introduction of the virus management at the enterprise are identified: opening, development, participation, diffusion, sustainability. The principles of introduction of the viral management in the enterprises of the coal industry are offered. It is established that the main idea of the viral management is to "infect" the organization and, mainly, employees with one or another "virus" in the form of a common idea or goal. It is indicated that the viral management assumes a certain automaticity of changes, internal "obsession" with this or other innovation, involvement of an informal personal factor.

  7. Sustainability in Transport Planning

    DEFF Research Database (Denmark)

    Gudmundsson, Henrik; Greve, Carsten

    Contribution to session J: Joint University Sustainability Initiatives. This session will provide an inspiring overview of interdisciplinary research and teaching activities on sustainability bridging DTU, KU, and CBS, and introduce the joint collaboration Copenhagen Sustainability Initiative (COSI...

  8. Sustainability : Politics and governance

    NARCIS (Netherlands)

    Heinrichs, Harald; Biermann, Frank

    2016-01-01

    he article gives an overview of global sustainability policy and politics. It is shown how international policy making on sustainable development has progressed from environmental policy toward recent approaches of Earth system governance. Key challenges of international sustainability politics are

  9. [Liver hemosiderosis study in chronic viral hepatitis].

    Science.gov (United States)

    Cojocariu, Camelia; Trifan, Anca; Mihailovici, Maria Sultana; Danciu, M; Stanciu, C

    2008-01-01

    In chronic viral hepatitis the histopathological exam can reveal the presence of liver iron deposits in 10 to 73% of patients. Iron deposits are usually found in Kupffer cells, in endothelial cells and portal macrophages, and extremely rarely in hepatocytes. To evaluate the incidence of hepatic hemosiderosis in chronic viral hepatitis. 549 morphopathological features of liver biopsy specimens performed in the Gastroenterology and Hepatology Institute IaSi, between January 1 2003 and December 31 2007 have been analyzed. Semiquantitative assessment of the degree of hepatic iron overload was performed and the localization of haemosiderin deposits: at the level of hepatocytes, the reticuloendothelial system or mixedly. The same anatomopathologist examined the blades and interpreted the results. The medium age of patients who underwent liver biopsy was 45.08 years +/- 10.045. Positive iron staining was found in 22.8% of cases, more frequently in males (31%), and in 91.82% of cases iron deposits were grade 1-2. The association of alcoholic etiology did not influence the incidence of hemosiderosis: 23% in patients with hepatitis and no ethanol exposure vs 25% in cases of strictly viral etiology. Deposits of haemosiderin were more frequent in viral hepatitis B (38.6%) than in viral hepatitis C (26.9%). In 34% of cases stainable iron was found only in reticuloendothelial system and in 46% of cases both in Kupffer cells and hepatocytes. Almost a quarter of chronic viral hepatitis cases are associated with liver deposits of haemosiderin, with features of secondary iron overload (deposits localized in the mesenchymal areas or mixedly). There is a higher risk of hemosiderosis in men, especially for those between 30 and 50. Liver iron overload levels in chronic viral hepatitis are, in most cases, low or medium, and the association with an alcoholic etiology does not influence the incidence of hemosiderosis in chronic viral hepatitis.

  10. Institute of Medicine's Report on Viral Hepatitis

    Centers for Disease Control (CDC) Podcasts

    2010-05-18

    In this podcast, Dr. John Ward, Director of CDC’s Division of Viral Hepatitis, discusses the 2010 report, Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C, from the Institute of Medicine.  Created: 5/18/2010 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 5/18/2010.

  11. Viral Oncolytic Therapeutics for Neoplastic Meningitis

    Science.gov (United States)

    2014-09-01

    Award Number: W81XWH-11-1-0387 TITLE: Viral Oncolytic Therapeutics for Neoplastic Meningitis PRINCIPAL INVESTIGATOR: Mikhail Papisov, PhD...SUBTITLE Viral Oncolytic Therapeutics for Neoplastic Meningitis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0387 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...for neoplastic meningitis ( meningeal metastasis of breast cancer). The proposed therapy will be based on direct (intrathecal) administration of

  12. Bacterial and Viral Fish Diseases in Turkey

    OpenAIRE

    Öztürk, Rafet Çagrı; Altınok, İlhan

    2014-01-01

    This review summarizes the state of knowledge about the major bacterial and viral pathogens of fish found in Turkey. It also considers diseases prevention and treatment. In this study, peer reviewed scientific articles, theses and dissertations, symposium proceedings, government records as well as recent books, which published between 1976 and 2013 were used as a source to compile dispersed literature. Bacterial and viral disease problems were investigated during this period in Turkey. Total ...

  13. Rapid and highly fieldable viral diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    McKnight, Timothy E.

    2016-12-20

    The present invention relates to a rapid, highly fieldable, nearly reagentless diagnostic to identify active RNA viral replication in a live, infected cells, and more particularly in leukocytes and tissue samples (including biopsies and nasal swabs) using an array of a plurality of vertically-aligned nanostructures that impale the cells and introduce a DNA reporter construct that is expressed and amplified in the presence of active viral replication.

  14. Textiles and clothing sustainability sustainable technologies

    CERN Document Server

    2017-01-01

    This is the first book to deal with the innovative technologies in the field of textiles and clothing sustainability. It details a number of sustainable and innovative technologies and highlights their implications in the clothing sector. There are currently various measures to achieve sustainability in the textiles and the clothing industry, including innovations in the manufacturing stage, which is the crux of this book.

  15. Complete histological regression of Kaposi's sarcoma following treatment with protease inhibitors despite persistence of HHV-8 in lesions

    DEFF Research Database (Denmark)

    Benfield, T L; Kirk, O; Elbrønd, B

    1998-01-01

    There is no current curative treatment for HIV-related Kaposi's sarcoma. The identification of human herpesvirus-8 as a possible aetiological agent suggests potential efficacy of anti-viral agents. We report here on the complete histological remission of Kaposi's sarcoma following treatment...... with protease inhibitors, even in patients with limited virological response and persistence of HHV-8....

  16. Persistent bovine pestivirus infection localized in the testes of an immuno-competent, non-viraemic bull

    NARCIS (Netherlands)

    Voges, H.; Horner, G.W.; Rowe, S.; Wellenberg, G.J.

    1998-01-01

    A post-pubertal bull on an artificial insemination station was found to be persistently shedding bovine viral diarrhoea virus (BVDV) in semen over a period of eleven months, while demonstrating no viraemia. Circulating antibodies to BVDV were consistently high, suggesting that the immune system was

  17. Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis c patients: a case control study

    Directory of Open Access Journals (Sweden)

    Levi-Drummer Rachel S

    2001-12-01

    Full Text Available Abstract Background High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied. Methods A new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15 with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9 with no dose reduction. Results Dose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group. Conclusions These findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C.

  18. Novel small-molecule inhibitors of hepatitis C virus entry block viral spread and promote viral clearance in cell culture.

    Directory of Open Access Journals (Sweden)

    Glen A Coburn

    Full Text Available Combinations of direct-acting anti-virals offer the potential to improve the efficacy, tolerability and duration of the current treatment regimen for hepatitis C virus (HCV infection. Viral entry represents a distinct therapeutic target that has been validated clinically for a number of pathogenic viruses. To discover novel inhibitors of HCV entry, we conducted a high throughput screen of a proprietary small-molecule compound library using HCV pseudoviral particle (HCVpp technology. We independently discovered and optimized a series of 1,3,5-triazine compounds that are potent, selective and non-cytotoxic inhibitors of HCV entry. Representative compounds fully suppress both cell-free virus and cell-to-cell spread of HCV in vitro. We demonstrate, for the first time, that long term treatment of an HCV cell culture with a potent entry inhibitor promotes sustained viral clearance in vitro. We have confirmed that a single amino acid variant, V719G, in the transmembrane domain of E2 is sufficient to confer resistance to multiple compounds from the triazine series. Resistance studies were extended by evaluating both the fusogenic properties and growth kinetics of drug-induced and natural amino acid variants in the HCVpp and HCV cell culture assays. Our results indicate that amino acid variations at position 719 incur a significant fitness penalty. Introduction of I719 into a genotype 1b envelope sequence did not affect HCV entry; however, the overall level of HCV replication was reduced compared to the parental genotype 1b/2a HCV strain. Consistent with these findings, I719 represents a significant fraction of the naturally occurring genotype 1b sequences. Importantly, I719, the most relevant natural polymorphism, did not significantly alter the susceptibility of HCV to the triazine compounds. The preclinical properties of these triazine compounds support further investigation of entry inhibitors as a potential novel therapy for HCV infection.

  19. Viral Metagenomics: MetaView Software

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, C; Smith, J

    2007-10-22

    The purpose of this report is to design and develop a tool for analysis of raw sequence read data from viral metagenomics experiments. The tool should compare read sequences of known viral nucleic acid sequence data and enable a user to attempt to determine, with some degree of confidence, what virus groups may be present in the sample. This project was conducted in two phases. In phase 1 we surveyed the literature and examined existing metagenomics tools to educate ourselves and to more precisely define the problem of analyzing raw read data from viral metagenomic experiments. In phase 2 we devised an approach and built a prototype code and database. This code takes viral metagenomic read data in fasta format as input and accesses all complete viral genomes from Kpath for sequence comparison. The system executes at the UNIX command line, producing output that is stored in an Oracle relational database. We provide here a description of the approach we came up with for handling un-assembled, short read data sets from viral metagenomics experiments. We include a discussion of the current MetaView code capabilities and additional functionality that we believe should be added, should additional funding be acquired to continue the work.

  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. Bioinformatics tools for analysing viral genomic data.

    Science.gov (United States)

    Orton, R J; Gu, Q; Hughes, J; Maabar, M; Modha, S; Vattipally, S B; Wilkie, G S; Davison, A J

    2016-04-01

    The field of viral genomics and bioinformatics is experiencing a strong resurgence due to high-throughput sequencing (HTS) technology, which enables the rapid and cost-effective sequencing and subsequent assembly of large numbers of viral genomes. In addition, the unprecedented power of HTS technologies has enabled the analysis of intra-host viral diversity and quasispecies dynamics in relation to important biological questions on viral transmission, vaccine resistance and host jumping. HTS also enables the rapid identification of both known and potentially new viruses from field and clinical samples, thus adding new tools to the fields of viral discovery and metagenomics. Bioinformatics has been central to the rise of HTS applications because new algorithms and software tools are continually needed to process and analyse the large, complex datasets generated in this rapidly evolving area. In this paper, the authors give a brief overview of the main bioinformatics tools available for viral genomic research, with a particular emphasis on HTS technologies and their main applications. They summarise the major steps in various HTS analyses, starting with quality control of raw reads and encompassing activities ranging from consensus and de novo genome assembly to variant calling and metagenomics, as well as RNA sequencing.

  2. Generating viral metagenomes from the coral holobiont

    Directory of Open Access Journals (Sweden)

    Karen Dawn Weynberg

    2014-05-01

    Full Text Available Reef-building corals comprise multipartite symbioses where the cnidarian animal is host to an array of eukaryotic and prokaryotic organisms, and the viruses that infect them. These viruses are critical elements of the coral holobiont, serving not only as agents of mortality, but also as potential vectors for lateral gene flow, and as elements encoding a variety of auxiliary metabolic functions. Consequently, understanding the functioning and health of the coral holobiont requires detailed knowledge of the associated viral assemblage and its function. Currently, the most tractable way of uncovering viral diversity and function is through metagenomic approaches, which is inherently difficult in corals because of the complex holobiont community, an extracellular mucus layer that all corals secrete, and the variety of sizes and structures of nucleic acids found in viruses. Here we present the first protocol for isolating, purifying and amplifying viral nucleic acids from corals based on mechanical disruption of cells. This method produces at least 50% higher yields of viral nucleic acids, has very low levels of cellular sequence contamination and captures wider viral diversity than previously used chemical-based extraction methods. We demonstrate that our mechanical-based method profiles a greater diversity of DNA and RNA genomes, including virus groups such as Retro-transcribing and ssRNA viruses, which are absent from metagenomes generated via chemical-based methods. In addition, we briefly present (and make publically available the first paired DNA and RNA viral metagenomes from the coral Acropora tenuis.

  3. Viral infection and host defense.

    Science.gov (United States)

    Carter, W A; De Clercq, E

    1974-12-27

    Double-stranded RNA, made as an intermediary substance in the replication of most, if not all, viruses, may play a much more important role in the pathogenesis and the recovery from virus infections than has hitherto been suspected. Apparently, dsRNA is used by both the challenge virus and the host cell in an attempt to gain "molecular control." Double-stranded RNA exerts a set of effects, which may be well balanced, not only at the level of the individual cell but also at the complex assemblage of these cells termed the organism (Fig. 1). In the cell, interferon synthesis is triggered, although interferon mRNA translation may not occur if dsRNA shuts off protein synthesis too quickly. In the whole organism, the disease severity will depend on how certain toxic reactions evoked by infection (such as cell necrosis and fever) are counterbalanced by an increase in the host defense mechanisms (for example, immune responsiveness and interferon production). Many aspects of the response, relating to either progress of, or recovery from, the disease, can be explained on the basis of a dsRNA. In addition to drawing attention to the biodynamic role of dsRNA, our hypothesis suggests specific experimental vectors designed to enhance our information on the molecular basis of the morbid process which occurs with viral infection. Finally, we suggest that, although the dsRNA molecule may be viewed as a rather simple unit structure, the opportunity for further diversity in the biological activity of a given dsRNA molecule always exists. Namely, each deviation from a perfectly double-helical arrangement introduces the possibility for emphasizing one biological reactivity at the expense of another. This latter structure-activity property may partially account for the extreme apparent diversity, commonly encountered, in the presentations of virologic illness. Appendix note added in proof. Subsequent to submission of this text, we have found that the potent mitogen effect of dsRNA for

  4. NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections.

    Science.gov (United States)

    Welsh, Raymond M; Waggoner, Stephen N

    2013-01-05

    Viral infections characteristically induce a cytokine-driven activated natural killer (NK) cell response that precedes an antigen-driven T cell response. These NK cells can restrain some but not all viral infections by attacking virus-infected cells and can thereby provide time for an effective T cell response to mobilize. Recent studies have revealed an additional immunoregulatory role for the NK cells, where they inhibit the size and functionality of the T cell response, regardless of whether the viruses are themselves sensitive to NK cells. This subsequent change in T cell dynamics can alter patterns of immunopathology and persistence and implicates NK cells as rheostat-like regulators of persistent infections. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Persistence Statements: Describing Digital Stickiness

    Directory of Open Access Journals (Sweden)

    John Kunze

    2017-08-01

    Full Text Available In this paper we present a draft vocabulary for making “persistence statements.” These are simple tools for pragmatically addressing the concern that anyone feels upon experiencing a broken web link. Scholars increasingly use scientific and cultural assets in digital form, but choosing which among many objects to cite for the long term can be difficult. There are few well-defined terms to describe the various kinds and qualities of persistence that object repositories and identifier resolvers do or don’t provide. Given an object’s identifier, one should be able to query a provider to retrieve human- and machine-readable information to help judge the level of service to expect and help gauge whether the identifier is durable enough, as a sort of long-term bet, to include in a citation. The vocabulary should enable providers to articulate persistence policies and set user expectations.

  6. T-cell exhaustion: understanding the interface of chronic viral and autoinflammatory diseases.

    Science.gov (United States)

    McKinney, Eoin F; Smith, Kenneth Gc

    2016-11-01

    During acute viral infection CD8 T cells rapidly expand before contracting down to a persistent memory population that confers long-lasting immunity. However when the antigen persists, such as during chronic viral infection, a dysfunctional process termed 'exhaustion' limits the antiviral response, facilitating ongoing viraemia and poor clinical outcome. CD8 T-cell exhaustion was originally identified in lymphocytic choriomeningitis virus infection of mice; however, new evidence has shown that exhaustion is associated with the control of a wide range of human chronic inflammatory states, including chronic viral infection, autoimmunity and cancer. Consequently, an understanding of the mechanisms controlling exhaustion during chronic infection may also indicate new strategies for controlling other chronic inflammatory diseases. In particular, the success of immune checkpoint blockade as a form of cancer immunotherapy has prompted renewed efforts to understand how T-cell immunity to chronic antigenic stimulation might similarly be measured or modulated in autoimmune diseases. Here we summarise the mechanisms controlling T-cell exhaustion and how they relate to the control of autoimmune responses, providing a future perspective on measuring or manipulating exhaustion to personalise therapy.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Energy Savings Lifetimes and Persistence

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, Ian M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schiller, Steven R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Todd, Annika [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Billingsley, Megan A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Goldman, Charles A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schwartz, Lisa C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-02-01

    This technical brief explains the concepts of energy savings lifetimes and savings persistence and discusses how program administrators use these factors to calculate savings for efficiency measures, programs and portfolios. Savings lifetime is the length of time that one or more energy efficiency measures or activities save energy, and savings persistence is the change in savings throughout the functional life of a given efficiency measure or activity. Savings lifetimes are essential for assessing the lifecycle benefits and cost effectiveness of efficiency activities and for forecasting loads in resource planning. The brief also provides estimates of savings lifetimes derived from a national collection of costs and savings for electric efficiency programs and portfolios.

  9. [Multiple ocular coloboma (MOC) with persistent pupillary membrane in the snow leopard (Panthera uncia)].

    Science.gov (United States)

    Schäffer, E; Wiesner, H; von Hegel, G

    1988-01-01

    In a litter of three snow leopards, bilateral colobomata of the upper temporal eyelids, bilateral persistent pupillary membranes and a unilateral coloboma of the optic nerve entrance are described as "Multiple Ocular Colobomata" (MOC). The causal pathogenesis of each of the colobomata is discussed comparatively. The colobomata of the eyelids, essential feature of the MOC syndrome in snow leopards, are most probably not of hereditary, but rather of intrauterine infectious viral origin.

  10. Molecular piracy: the viral link to carcinogenesis.

    Science.gov (United States)

    Flaitz, C M; Hicks, M J

    1998-11-01

    The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous

  11. 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.

  12. APLASTIC ANEMIA AND VIRAL HEPATITIS

    Directory of Open Access Journals (Sweden)

    Laura Cudillo

    2009-11-01

    target organ of the immune  response is the liver as suggested by the time interval between hepatitis and the onset of bone marrow failure.

    Liver histology is characterized by T cell infiltrating the parenchyma as reported in acute hepatitis.

    Recently in HAA it has been demonstrated intrahepatic  and blood lymphocytes with  T cell repertoire similar to that of confirmed viral acute hepatitis. The expanded T cell clones return to a normal distribution after response to immunosuppressive treatment, suggesting the antigen or T cell clearance. Therapeutic options are the same as acquired aplastic anemia.

  13. Live, Attenuated Venezuelan Equine Encephalitis Virus Vaccine (TC83) Causes Persistent Brain Infection in Mice with Non-functional αβ T-Cells

    Science.gov (United States)

    Taylor, Katherine; Kolokoltsova, Olga; Ronca, Shannon E.; Estes, Mark; Paessler, Slobodan

    2017-01-01

    Intranasal infection with vaccine strain of Venezuelan equine encephalitis virus (TC83) caused persistent viral infection in the brains of mice without functional αβ T-cells (αβ-TCR -/-). Remarkably, viral kinetics, host response gene transcripts and symptomatic disease are similar between αβ-TCR -/- and wild-type C57BL/6 (WT) mice during acute phase of infection [0–13 days post-infection (dpi)]. While WT mice clear infectious virus in the brain by 13 dpi, αβ-TCR -/- maintain infectious virus in the brain to 92 dpi. Persistent brain infection in αβ-TCR -/- correlated with inflammatory infiltrates and elevated cytokine protein levels in the brain at later time points. Persistent brain infection of αβ-TCR -/- mice provides a novel model to study prolonged alphaviral infection as well as the effects and biomarkers of long-term viral inflammation in the brain. PMID:28184218

  14. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  15. Auditory sustained field responses to periodic noise

    Directory of Open Access Journals (Sweden)

    Keceli Sumru

    2012-01-01

    Full Text Available Abstract Background Auditory sustained responses have been recently suggested to reflect neural processing of speech sounds in the auditory cortex. As periodic fluctuations below the pitch range are important for speech perception, it is necessary to investigate how low frequency periodic sounds are processed in the human auditory cortex. Auditory sustained responses have been shown to be sensitive to temporal regularity but the relationship between the amplitudes of auditory evoked sustained responses and the repetitive rates of auditory inputs remains elusive. As the temporal and spectral features of sounds enhance different components of sustained responses, previous studies with click trains and vowel stimuli presented diverging results. In order to investigate the effect of repetition rate on cortical responses, we analyzed the auditory sustained fields evoked by periodic and aperiodic noises using magnetoencephalography. Results Sustained fields were elicited by white noise and repeating frozen noise stimuli with repetition rates of 5-, 10-, 50-, 200- and 500 Hz. The sustained field amplitudes were significantly larger for all the periodic stimuli than for white noise. Although the sustained field amplitudes showed a rising and falling pattern within the repetition rate range, the response amplitudes to 5 Hz repetition rate were significantly larger than to 500 Hz. Conclusions The enhanced sustained field responses to periodic noises show that cortical sensitivity to periodic sounds is maintained for a wide range of repetition rates. Persistence of periodicity sensitivity below the pitch range suggests that in addition to processing the fundamental frequency of voice, sustained field generators can also resolve low frequency temporal modulations in speech envelope.

  16. Sustainability transition dynamics: Towards overcoming policy resistance

    OpenAIRE

    Gooyert, V. de; Rouwette, E.A.J.A.; van Kranenburg, H.L.; Freeman, R.E.; Breen, H.J. van

    2016-01-01

    Sustainability transitions receive major scholarly attention, often explicitly with the intention to develop policy recommendations aimed towards progressing such transitions. Despite these efforts, many implemented transition policies have not been able to meet expectations. This tendency of systems to defeat the policies that have been designed to improve them is known as ‘policy resistance’. This paper addresses the question how we can explain the persistence of policy resistance in the co...

  17. Persistence of experimental Rocio virus infection in the golden hamster (Mesocricetus auratus

    Directory of Open Access Journals (Sweden)

    Daniele Freitas Henriques

    2012-08-01

    Full Text Available Rocio virus (ROCV is an encephalitic flavivirus endemic to Brazil. Experimental flavivirus infections have previously demonstrated a persistent infection and, in this study, we investigated the persistence of ROCV infection in golden hamsters (Mesocricetus auratus. The hamsters were infected intraperitoneally with 9.8 LD50/0.02 mL of ROCV and later anaesthetised and sacrificed at various time points over a 120-day period to collect of blood, urine and organ samples. The viral titres were quantified by real-time-polymerase chain reaction (qRT-PCR. The specimens were used to infect Vero cells and ROCV antigens in the cells were detected by immunefluorescence assay. The levels of antibodies were determined by the haemagglutination inhibition technique. A histopathological examination was performed on the tissues by staining with haematoxylin-eosin and detecting viral antigens by immunohistochemistry (IHC. ROCV induced a strong immune response and was pathogenic in hamsters through neuroinvasion. ROCV was recovered from Vero cells exposed to samples from the viscera, brain, blood, serum and urine and was detected by qRT-PCR in the brain, liver and blood for three months after infection. ROCV induced histopathological changes and the expression of viral antigens, which were detected by IHC in the liver, kidney, lung and brain up to four months after infection. These findings show that ROCV is pathogenic to golden hamsters and has the capacity to cause persistent infection in animals after intraperitoneal infection.

  18. Persistent infections support maintenance of a coronavirus in a population of Australian bats (Myotis macropus).

    Science.gov (United States)

    Jeong, J; Smith, C S; Peel, A J; Plowright, R K; Kerlin, D H; McBroom, J; McCallum, H

    2017-07-01

    Understanding viral transmission dynamics within populations of reservoir hosts can facilitate greater knowledge of the spillover of emerging infectious diseases. While bat-borne viruses are of concern to public health, investigations into their dynamics have been limited by a lack of longitudinal data from individual bats. Here, we examine capture-mark-recapture (CMR) data from a species of Australian bat (Myotis macropus) infected with a putative novel Alphacoronavirus within a Bayesian framework. Then, we developed epidemic models to estimate the effect of persistently infectious individuals (which shed viruses for extensive periods) on the probability of viral maintenance within the study population. We found that the CMR data analysis supported grouping of infectious bats into persistently and transiently infectious bats. Maintenance of coronavirus within the study population was more likely in an epidemic model that included both persistently and transiently infectious bats, compared with the epidemic model with non-grouping of bats. These findings, using rare CMR data from longitudinal samples of individual bats, increase our understanding of transmission dynamics of bat viral infectious diseases.

  19. [Organic agriculture and sustainable development].

    Science.gov (United States)

    Li, Yu; Wang, Gang

    2004-12-01

    Basing on the research and practice of organic agriculture at home and abroad, this paper discussed the objectives of developing green food and the principles that must be persisted in the practice in China. In the light of the arguments concerning with sustainable agriculture, we also discussed the significance of "alternative agriculture" in theory and practice. Compared with conventional high-intensity agriculture, the production approaches of organic alternatives can improve soil fertility and have fewer detrimental effects on the environment. It is unclear whether conventional agriculture can be sustained because of the shortcomings presented in this paper, and it has taken scientists approximately one century to research and practice organic farming as a representative of alternative agriculture. The development of green food in China has only gone through more than ten years, and there would be some practical and theoretical effects on the development of China's green food if we exploit an environment-friendly production pattern of organic agriculture which majors in keeping human health and maintaining sustainable agriculture.

  20. Assessing sustainable remediation frameworks using sustainability principles.

    Science.gov (United States)

    Ridsdale, D Reanne; Noble, Bram F

    2016-12-15

    The remediation industry has grown exponentially in recent decades. International organizations of practitioners and remediation experts have developed several frameworks for integrating sustainability into remediation projects; however, there has been limited attention to how sustainability is approached and operationalized in sustainable remediation frameworks and practices - or whether sustainability plays any meaningful role at all in sustainable remediation. This paper examines how sustainability is represented in remediation frameworks and the guidance provided for practical application. Seven broad sustainability principles and review criteria are proposed and applied to a sample of six international remediation frameworks. Not all review criteria were equally satisfied and none of the frameworks fully met all criteria; however, the best performing frameworks were those identified as sustainability remediation frameworks. Intra-generational equity was addressed by all frameworks. Integrating social, economic and biophysical components beyond triple-bottom-line indicators was explicitly addressed only by the sustainable remediation frameworks. No frameworks provided principle- or rule-based guidance for dealing with trade-offs in sustainability decisions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Persistently high Epstein-Barr virus (EBV) loads in peripheral blood lymphocytes from patients with chronic active EBV infection.

    Science.gov (United States)

    Maeda, A; Wakiguchi, H; Yokoyama, W; Hisakawa, H; Tomoda, T; Kurashige, T

    1999-04-01

    Chronic active Epstein-Barr virus infection (CAEBV) is a severe illness with unusual EBV activation that persists for years, and its pathogenesis is largely unknown. After the creation of an accurate and reproducible polymerase chain reaction system to quantify EBV DNA, virus loads in peripheral blood lymphocytes (PBL) were determined in 54 children: 15 with CAEBV, 16 with infectious mononucleosis (IM), and 23 healthy children. Children with CAEBV and those with IM had high virus loads. Lower loads were detected in 47% of seropositive healthy donors. There were two distinct differences between children with CAEBV and those with IM: The former had greater viral replication (10(3)-10(7) copies/2.5x10(5) PBL) than those with IM, and viral replication declined in children with IM whereas active replication persisted for years in subjects with CAEBV. Persisting high virus loads are a possible diagnostic criterion for CAEBV. EBV loads may enable classification and prognosis of EBV infections.

  2. Cytomegalovirus pp65 limits dissemination but is dispensable for persistence

    Energy Technology Data Exchange (ETDEWEB)

    Malouli, Daniel; Hansen, Scott G.; Nakayasu, Ernesto S.; Marshall, Emily E.; Hughes, Colette M.; Ventura, Abigail B.; Gilbride, Roxanne M.; Lewis, Matthew S.; Xu, Guangwu; Kreklywich, Craig; Whizin, Nathan; Fischer, Miranda; Legasse, Alfred W.; Viswanathan, Kasinath; Siess, Don; Camp, David G.; Axthelm, Michael K.; Kahl, Christoph; DeFilippis, Victor R.; Smith, Richard D.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus

    2014-04-01

    The tegument phosphoprotein pp65 (UL83) is the most abundant virion protein in human cytomegalovirus (HCMV). Since pp65 is immunodominant in persistently infected individuals, subunit vaccines against HCMV often include pp65 as T cell stimulatory component. Although HCMV pp65 is non-essential for viral growth in vitro it is thought to have an important role in primary and persistent infection since pp65 displays multiple immunomodulatory functions. To determine whether pp65 is required for infection and to evaluate its role in natural and vaccination-induced immunity we generated a rhesus CMV lacking both homologues, pp65a (Rh111) and pp65b (Rh112). Lack of pp65 resulted in a slight growth defect in vitro and an increase of defective particle formation. However, most pp65-deleted virions in the supernatant were phenotypically normal and proteomics analysis revealed that the ratios of the remaining viral proteins were largely unchanged. RhCMV Δpp65ab was able to persistently infect CMV-negative rhesus macaques (RM) and to super-infect RM previously infected with CMV. To determine whether T cells against pp65 are essential for protection against CMV, we challenged Δpp65ab-infected animals with RhCMV ΔUS2-11, a viral recombinant that lacks inhibitors of MHC-I antigen presentation and is thus unable to overcome CMV-specific T cell immunity. Despite a complete lack of pp65-specific T cells, Δpp65ab protected against ΔUS2-11 challenge suggesting that pp65-specific T cells are not essential for T cell immunity against CMV. Using the same approach we further demonstrate that pp65b-specific T cells, induced by heterologous prime/boost vaccination, are not sufficient to protect against ΔUS2-11 challenge. Our data provides a new approach to test the efficacy of subunit vaccine candidates and suggest that pp65 vaccines are insufficient to induce a T cell response that recapitulates the protective effect of natural infection.

  3. Organizing for Sustainability

    Science.gov (United States)

    Brown, William M.; Hamburger, Michael W.

    2012-01-01

    A successful campus sustainability effort catalyzes broad engagement of the campus community and integration of sustainability principles into the academic and operational components of campus life. Although many universities have embraced sustainability as a new core value, others have been more sluggish in adopting sustainability principles to…

  4. Technology and sustainability

    NARCIS (Netherlands)

    Kroeze, C.; Boersema, J.J.; Tellegen, E.; Cremers, A.

    2011-01-01

    In ten essays, this book addresses a broad range of issues related to the interplay of sustainability and technology. How do population growth and technology relate to sustainable development? Can globalization be reconciled with sustainable development? Is sustainability a subjective or an

  5. The role of myelin in Theiler's virus persistence in the central nervous system.

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Roussarie

    2007-02-01

    Full Text Available Theiler's virus, a picornavirus, persists for life in the central nervous system of mouse and causes a demyelinating disease that is a model for multiple sclerosis. The virus infects neurons first but persists in white matter glial cells, mainly oligodendrocytes and macrophages. The mechanism, by which the virus traffics from neurons to glial cells, and the respective roles of oligodendrocytes and macrophages in persistence are poorly understood. We took advantage of our previous finding that the shiverer mouse, a mutant with a deletion in the myelin basic protein gene (Mbp, is resistant to persistent infection to examine the role of myelin in persistence. Using immune chimeras, we show that resistance is not mediated by immune responses or by an efficient recruitment of inflammatory cells into the central nervous system. With both in vivo and in vitro experiments, we show that the mutation does not impair the permissiveness of neurons, oligodendrocytes, and macrophages to the virus. We demonstrate that viral antigens are present in cytoplasmic channels of myelin during persistent infection of wild-type mice. Using the optic nerve as a model, we show that the virus traffics from the axons of retinal ganglion cells to the cytoplasmic channels of myelin, and that this traffic is impaired by the shiverer mutation. These results uncover an unsuspected axon to myelin traffic of Theiler's virus and the essential role played by the infection of myelin/oligodendrocyte in persistence.

  6. Coping with persistent environmental problems

    DEFF Research Database (Denmark)

    Varjopuro, Riku; Andrulewicz, Eugeniusz; Brandt, Urs Steiner

    2014-01-01

    ABSTRACT In this paper we focus on systemic delays in the Baltic Sea that cause the problem of eutrophication to persist. These problems are demonstrated in our study by addressing three types of delays: (1) decision delay: the time it takes for an idea or perceived need to be launched as a polic...

  7. Long memory and changing persistence

    DEFF Research Database (Denmark)

    Kruse, Robinson; Sibbertsen, Philipp

    We study the empirical behaviour of semi-parametric log-periodogram estimation for long memory models when the true process exhibits a change in persistence. Simulation results confirm theoretical arguments which suggest that evidence for long memory is likely to be found. A recently proposed test...

  8. On persistently positively expansive maps

    Directory of Open Access Journals (Sweden)

    Alexander Arbieto

    2010-06-01

    Full Text Available In this paper, we prove that any C¹-persistently positively expansive map is expanding. This improves a result due to Sakai (Sakai 2004.Neste artigo, mostramos que todo mapa C¹-persistentemente positivamente expansivo e expansor. Isto melhora um resultado devido a Sakai (Sakai 2004.

  9. Hepatic sarcoidosis complicating treatment-naive viral hepatitis

    OpenAIRE

    Aravinthan, Aloysious; Gelson, William; Limbu, Anita; Brais, Rebecca; Richardson, Paul

    2012-01-01

    Hepatic sarcoidosis is usually asymptomatic but rarely leads to adverse liver-related outcome. Co-existence of viral hepatitis and hepatic sarcoidosis is a rare, but recognised phenomenon. Obtaining a balance between immune suppression and anti-viral therapy may be problematic. Immunosuppression in the presence of viral hepatitis can lead to rapid deterioration of liver disease. Similarly, anti-viral therapy may exacerbate granulomatous hepatitis. Here we present two cases of viral hepatitis ...

  10. Viral Hepatitis and Liver Cancer on the Island of Guam

    OpenAIRE

    Haddock, RL; Paulino, YC; Bordallo, R

    2013-01-01

    Patient records from the Guam Cancer Registry were compared with patients listed in a health department viral hepatitis case registry. The number of liver cancer and viral hepatitis cases were compared by ethnicity. Hepatitis C was the form of viral hepatitis most common among liver cancer cases on Guam (63.3% of viral hepatitis-associated liver cancer cases). Since viral hepatitis is an important cause of liver cancer, studies such as the present one may provide the information necessary to ...

  11. Molecular imaging of oncolytic viral therapy

    Directory of Open Access Journals (Sweden)

    Dana Haddad

    2014-01-01

    Full Text Available Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy.

  12. View and review on viral oncology research

    Directory of Open Access Journals (Sweden)

    Parolin Cristina

    2010-05-01

    Full Text Available Abstract To date, almost one and a half million cases of cancer are diagnosed every year in the US and nearly 560,000 Americans are expected to die of cancer in the current year, more than 1,500 people a day (data from the American Cancer Society at http://www.cancer.org/. According to the World Health Organization (WHO, roughly 20% of all cancers worldwide results from chronic infections; in particular, up to 15% of human cancers is characterized by a viral aetiology with higher incidence in Developing Countries. The link between viruses and cancer was one of the pivotal discoveries in cancer research during the past Century. Indeed, the infectious nature of specific tumors has important implications in terms of their prevention, diagnosis, and therapy. In the 21st Century, the research on viral oncology field continues to be vigorous, with new significant and original studies on viral oncogenesis and translational research from basic virology to treatment of cancer. This review will cover different viral oncology aspects, starting from the history of viral oncology and moving to the peculiar features of oncogenic RNA and DNA viruses, with a special focus on human pathogens.

  13. Pediatric Viral Exanthema: A Review Article

    Directory of Open Access Journals (Sweden)

    Mohammed Jafar Saffar

    2017-04-01

    Full Text Available Context Many diseases caused by viral agents are associated with fever and cutaneous manifestations. Viral exanthema is a widespread nonspecific skin rash, commonly characterized by generalized eruption of erythematous macules and papular lesions. Although these rashes are mostly benign and self-limited, some may be serious and life-threatening. Differentiation between severe and benign types is clinically important and life-saving. Evidence Acquisition In this narrative review, electronic databases, including Google Scholar, Science Direct, PubMed (including Medline, Web of Science, Scientific Information Database, and Scopus, were searched. We conducted a narrative review of papers published on pediatric viral exanthema during 2000 - 2016. The used keywords included “viral exanthema”, “fever”, and “skin rash”. Articles on skin rash, caused by drug reactions or nonviral exanthema, were excluded. Results Different viral agents can cause different types of skin reactions. Cutaneous manifestations and skin rashes can be categorized, based on the form of the rash (macular, papular, vesicular, blistery, petechial, and purpuric or the general term, which denotes illnesses such as measles-like morbilliform rash, rubella or rubelliform rash, and scarlatiniform rash, a scarlet-fever like infection. Conclusions Based on the findings, a systematic approach relying on accurate history-taking and analysis of epidemiological cues and rash characteristics is of great significance.

  14. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...

  15. Sustainable Investment. Literature Overview

    Energy Technology Data Exchange (ETDEWEB)

    Weda, J.; Kerste, M.; Rosenboom, N.

    2010-08-15

    Corporate Social Responsibility (CSR), or sustainability at the company level, entails incorporating ecological (environmental stakeholders) and social aspects (stakeholders other than shareholders and environmental stakeholders) when doing business. Socially Responsible Investment (SRI) concerns sustainability at the investment, fund or portfolio level and involves screening the sustainability of companies before investing in them. This report highlights leading literature and empirical findings on 'sustainable investment', amongst others addressing the economic rationale for CSR and SRI. This report is part of a set of SEO-reports on finance and sustainability. The other reports deal with: Financing the Transition to Sustainable Energy; Carbon Trading; Innovations in financing environmental and social sustainability.

  16. Avian influenza H5N1 viral and bird migration networks in Asia

    Science.gov (United States)

    Tian, Huaivu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Newman, Scott H.; Takekawa, John Y.; Prosser, Diann J.; Xiao, Xiangming; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T.; Xu, Bing

    2015-01-01

    The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia.

  17. Persistence

    DEFF Research Database (Denmark)

    Hansen, Kis Boisen

    2012-01-01

    The note shows an example of an architure for buildin g stand-alone program, where the programming language is object oriented and the databas system is a relational database system. Together with the notes is an example program....

  18. Viral vector-based influenza vaccines

    Science.gov (United States)

    de Vries, Rory D.; Rimmelzwaan, Guus F.

    2016-01-01

    ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

  19. Shedding new light on viral photosynthesis.

    Science.gov (United States)

    Puxty, Richard J; Millard, Andrew D; Evans, David J; Scanlan, David J

    2015-10-01

    Viruses infecting the environmentally important marine cyanobacteria Prochlorococcus and Synechococcus encode 'auxiliary metabolic genes' (AMGs) involved in the light and dark reactions of photosynthesis. Here, we discuss progress on the inventory of such AMGs in the ever-increasing number of viral genome sequences as well as in metagenomic datasets. We contextualise these gene acquisitions with reference to a hypothesised fitness gain to the phage. We also report new evidence with regard to the sequence and predicted structural properties of viral petE genes encoding the soluble electron carrier plastocyanin. Viral copies of PetE exhibit extensive modifications to the N-terminal signal peptide and possess several novel residues in a region responsible for interaction with redox partners. We also highlight potential knowledge gaps in this field and discuss future opportunities to discover novel phage-host interactions involved in the photosynthetic process.

  20. V-GAP: Viral genome assembly pipeline

    KAUST Repository

    Nakamura, Yoji

    2015-10-22

    Next-generation sequencing technologies have allowed the rapid determination of the complete genomes of many organisms. Although shotgun sequences from large genome organisms are still difficult to reconstruct perfect contigs each of which represents a full chromosome, those from small genomes have been assembled successfully into a very small number of contigs. In this study, we show that shotgun reads from phage genomes can be reconstructed into a single contig by controlling the number of read sequences used in de novo assembly. We have developed a pipeline to assemble small viral genomes with good reliability using a resampling method from shotgun data. This pipeline, named V-GAP (Viral Genome Assembly Pipeline), will contribute to the rapid genome typing of viruses, which are highly divergent, and thus will meet the increasing need for viral genome comparisons in metagenomic studies.

  1. [Promotion of Porphyromonas gingivalis to viral disease].

    Science.gov (United States)

    Tiantian, Meng; Xin, Li

    2016-08-01

    Chronic periodontitis is one of the most common oral diseases in humans, the main recognized pathogenic bac-terium of which is the Porphyromonas gingivalis. Various types of viruses have been detected in periodontal disease in situ, and the joint action of viral and bacterial pathogens infection mechanism are complicated. Porphyromonas gingivalis has the characteristics resulting from the interaction with a variety of bacterium viruses, which may be the reason for chronic perio-dontitis being a protracted disease associated with a variety of systemic diseases. In this paper, we reviewed the relationship between Porphyromonas gingivalis and viral diseases to provide a new idea for the treatment of patients with periodontal disease and viral infections.

  2. Cochrane Corner: Corticosteroids for viral myocarditis.

    Science.gov (United States)

    Caldeira, Daniel; Lopes, Luís R; Vaz-Carneiro, António; Costa, João

    2015-01-01

    The causes of myocarditis are diverse, but a viral etiology is the most common. In this systematic review by the Cochrane Collaboration, the authors assessed the efficacy of corticosteroid therapy in patients with viral myocarditis. Eight randomized controlled trials with 719 patients (two trials in pediatric populations) were included for analysis. Pooled results did not show significant differences in mortality with the use of corticosteroids. Patients on corticosteroid therapy had significantly higher post-treatment left ventricular ejection fraction values compared to control. These results are limited by the significant heterogeneity associated with clinical trials. The best available evidence does not support the routine use of corticosteroids in patients with viral myocarditis. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  3. Hepatitis viral load correlates to glutathione levels.

    Science.gov (United States)

    1998-01-01

    Several recent scientific articles have found a direct correlation between Glutathione levels and viral activity for hepatitis B and C. When viral load increases, Glutathione decreases. Researchers from Germany report that adding NAC (N-acetyl cysteine) to HBV producing cells lines can reduce hepatitis viral load 50 fold. Glutathione is used by the liver to help break down toxins. Patients who have chronic infection for more than 90 days should ask their physicians to check their Glutathione levels. A test kit is available from ImmunoSciences Labs; contact information is included. An amino acid, L-Glutamine, can be used with Alpha Lipoic Acid and NAC to increase Glutathione levels. Chlorophyll also offers benefits to people with hepatitis and other infections. Instructions on how to use a special retention enema containing chlorophyll, water, and apple cider vinegar are provided.

  4. Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein.

    Directory of Open Access Journals (Sweden)

    Simon Swingler

    2007-09-01

    Full Text Available Viruses have evolved strategies to protect infected cells from apoptotic clearance. We present evidence that HIV-1 possesses a mechanism to protect infected macrophages from the apoptotic effects of the death ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand. In HIV-1-infected macrophages, the viral envelope protein induced macrophage colony-stimulating factor (M-CSF. This pro-survival cytokine downregulated the TRAIL receptor TRAIL-R1/DR4 and upregulated the anti-apoptotic genes Bfl-1 and Mcl-1. Inhibition of M-CSF activity or silencing of Bfl-1 and Mcl-1 rendered infected macrophages highly susceptible to TRAIL. The anti-cancer agent Imatinib inhibited M-CSF receptor activation and restored the apoptotic sensitivity of HIV-1-infected macrophages, suggesting a novel strategy to curtail viral persistence in the macrophage reservoir.

  5. VISMapper: ultra-fast exhaustive cartography of viral insertion sites for gene therapy.

    Science.gov (United States)

    Juanes, José M; Gallego, Asunción; Tárraga, Joaquín; Chaves, Felipe J; Marín-Garcia, Pablo; Medina, Ignacio; Arnau, Vicente; Dopazo, Joaquín

    2017-09-20

    The possibility of integrating viral vectors to become a persistent part of the host genome makes them a crucial element of clinical gene therapy. However, viral integration has associated risks, such as the unintentional activation of oncogenes that can result in cancer. Therefore, the analysis of integration sites of retroviral vectors is a crucial step in developing safer vectors for therapeutic use. Here we present VISMapper, a vector integration site analysis web server, to analyze next-generation sequencing data for retroviral vector integration sites. VISMapper can be found at: http://vismapper.babelomics.org . Because it uses novel mapping algorithms VISMapper is remarkably faster than previous available programs. It also provides a useful graphical interface to analyze the integration sites found in the genomic context.

  6. Adenoviral and adeno-associated viral vector mediated gene transfer in the guinea pig cochlea.

    Science.gov (United States)

    Li Duan, Mao; Bordet, Thierry; Mezzina, Mauro; Kahn, Axel; Ulfendahl, Mats

    2002-07-19

    Peripheral sensorineural hearing loss is a very common inner ear disorder affecting nearly 10% of the population. At present there is no cure for this disorder but gene therapy has been suggested as a potentially effective method for clinical treatment in the future. Thus we investigated the effectiveness of adenoviral (Ad) and adeno-associated viral (AAV) vectors to transduce the cochlea of guinea pigs. After direct injection into the basal turn of the cochlea, we found that both Ad and AAV vectors coding for the reporter genes lacZ or GFP readily transduced spiral ganglion cells. In addition, some transgene expression was detected in the stria vascularis after AAV-GFP injection. Gene expression persisted at least 8 weeks after viral vector injection. Present findings will help to develop future gene therapy protocols in the inner ear by using Ad and AAV coding for neurotrophins such as NT-3, BDNF, GDNF and VEGF.

  7. Pluralism in Search of Sustainability: Ethics, Knowledge and Methdology in Sustainability Science

    Directory of Open Access Journals (Sweden)

    Ellinor Isgren

    2017-02-01

    Full Text Available Sustainability Science is an emerging, transdisciplinary academic field that aims to help build a sustainable global society by drawing on and integrating research from the humanities and the social, natural, medical and engineering sciences. Academic knowledge is combined with that from relevant actors from outside academia, such as policy-makers, businesses, social organizations and citizens. The field is focused on examining the interactions between human, environmental, and engineered systems to understand and contribute to solutions for complex challenges that threaten the future of humanity and the integrity of the life support systems of the planet, such as climate change, biodiversity loss, pollution, and land and water degradation. Since its inception in around the year 2000, and as expressed by a range of proponents in the field, sustainability science has become an established international platform for interdisciplinary research on complex social problems [1]. This has been done by exploring ways to promote ‘greater integration and cooperation in fulfilling the sustainability science mandate’ [2]. Sustainability science has thereby become an extremely diverse academic field, yet one with an explicit normative mission. After nearly two decades of sustainability research, it is important to reflect on a major question: what critical knowledge can we gain from sustainability science research on persistent socio-ecological problems and new sustainability challenges?

  8. IFITM proteins restrict viral membrane hemifusion.

    Directory of Open Access Journals (Sweden)

    Kun Li

    2013-01-01

    Full Text Available The interferon-inducible transmembrane (IFITM protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. Here we provide evidence that IFITM proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. IFITM1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; IFITM2 and IFITM3 also strongly inhibited their fusion, with efficiency somewhat dependent on cell types. Furthermore, treatment of cells with IFN also markedly inhibited viral membrane fusion and entry. By using the Jaagsiekte sheep retrovirus envelope and influenza A virus hemagglutinin as models for study, we showed that IFITM-mediated restriction on membrane fusion is not at the steps of receptor- and/or low pH-mediated triggering; instead, the creation of hemifusion was essentially blocked by IFITMs. Chlorpromazine (CPZ, a chemical known to promote the transition from hemifusion to full fusion, was unable to rescue the IFITM-mediated restriction on fusion. In contrast, oleic acid (OA, a lipid analog that generates negative spontaneous curvature and thereby promotes hemifusion, virtually overcame the restriction. To explore the possible effect of IFITM proteins on membrane molecular order and fluidity, we performed fluorescence labeling with Laurdan, in conjunction with two-photon laser scanning and fluorescence-lifetime imaging microscopy (FLIM. We observed that the generalized polarizations (GPs and fluorescence lifetimes of cell membranes expressing IFITM proteins were greatly enhanced, indicating higher molecularly ordered and less fluidized membranes. Collectively, our data demonstrated that IFITM proteins suppress viral membrane fusion before the creation of hemifusion, and suggested that they may do so by reducing membrane fluidity and conferring a positive

  9. The fecal viral flora of wild rodents.

    Directory of Open Access Journals (Sweden)

    Tung G Phan

    2011-09-01

    Full Text Available The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in

  10. Acute Viral Hepatitis in Pediatric Age Groups

    Directory of Open Access Journals (Sweden)

    Sudhamshu KC

    2014-03-01

    Full Text Available Introduction: Our clinical experience showed that there has been no decrease in pediatric cases of acute viral hepatitis in Kathmandu. The objective of the study was to analyze the etiology, clinical features, laboratory parameters, sonological findings and other to determine the probable prognostic factors of Acute Viral Hepatitis in pediatric population. Methods: Consecutive patients of suspected Acute Viral Hepatitis, below the age of 15 years, attending the liver clinic between January 2006 and December2010were studied. After clinical examination they were subjected to blood tests and ultrasound examination of abdomen. The patients were divided in 3 age groups; 0–5, 5–10 and 5–15 years. Clinical features, laboratory parameters, ultrasound findings were compared in three age groups. Results: Etiology of Acute Viral Hepatitis was Hepatitis A virus 266 (85%, Hepatitis E virus in 24 (8%, Hepatitis B virus in 15 (5%. In 7(2% patients etiology was unknown. Three patients went to acute liver failure but improved with conservative treatment. There was no statistical difference in most of the parameters studied in different age groups. Ascites was more common in 5-10 years age group. Patients with secondary bacterial infection, ultrasound evidence of prominent biliary tree and ascites were associated with increased duration of illness. Patients with history of herbal medications had prolonged cholestasis. Conclusions: Hepatitis A is most common cause of Acute Viral Hepatitis in pediatric population. Improper use of herbal medications, secondary bacterial infection and faulty dietary intake was associated with prolonged illness. Patients with prominent biliary radicals should be treated with antibiotics even with normal blood counts for earlier recovery. Keywords: Acute viral hepatitis; hepatitis A; hepatitis E; herbal medications.

  11. Molecular analyses detect natural coinfection of water buffaloes (Bubalus bubalis with bovine viral diarrhea viruses (BVDV in serologically negative animals

    Directory of Open Access Journals (Sweden)

    María I Craig

    2015-06-01

    Full Text Available Infection of water buffaloes (Bubalus bubalis with bovine viral diarrhea viruses (BVDV has been confirmed in several studies by serological and molecular techniques. In order to determine the presence of persistently infected animals and circulating species and subtypes of BVDV we conducted this study on a buffalo herd, whose habitat was shared with bovine cattle (Bossp.. Our serological results showed a high level of positivity for BVDV-1 and BVDV-2 within the buffalo herd. The molecular analyses of blood samples in serologically negative animals revealed the presence of viral nucleic acid, confirming the existence of persistent infection in the buffaloes. Cloning and sequencing of the 5′ UTR of some of these samples revealed the presence of naturally mix-infected buffaloes with at least two different subtypes (1a and 1b, and also with both BVDV species (BVDV-1 and BVDV-2.

  12. Tumor-necrosis factor impairs CD4(+) T cell-mediated immunological control in chronic viral infection.

    Science.gov (United States)

    Beyer, Marc; Abdullah, Zeinab; Chemnitz, Jens M; Maisel, Daniela; Sander, Jil; Lehmann, Clara; Thabet, Yasser; Shinde, Prashant V; Schmidleithner, Lisa; Köhne, Maren; Trebicka, Jonel; Schierwagen, Robert; Hofmann, Andrea; Popov, Alexey; Lang, Karl S; Oxenius, Annette; Buch, Thorsten; Kurts, Christian; Heikenwalder, Mathias; Fätkenheuer, Gerd; Lang, Philipp A; Hartmann, Pia; Knolle, Percy A; Schultze, Joachim L

    2016-05-01

    Persistent viral infections are characterized by the simultaneous presence of chronic inflammation and T cell dysfunction. In prototypic models of chronicity--infection with human immunodeficiency virus (HIV) or lymphocytic choriomeningitis virus (LCMV)--we used transcriptome-based modeling to reveal that CD4(+) T cells were co-exposed not only to multiple inhibitory signals but also to tumor-necrosis factor (TNF). Blockade of TNF during chronic infection with LCMV abrogated the inhibitory gene-expression signature in CD4(+) T cells, including reduced expression of the inhibitory receptor PD-1, and reconstituted virus-specific immunity, which led to control of infection. Preventing signaling via the TNF receptor selectively in T cells sufficed to induce these effects. Targeted immunological interventions to disrupt the TNF-mediated link between chronic inflammation and T cell dysfunction might therefore lead to therapies to overcome persistent viral infection.

  13. Viral infections stimulate the metabolism and shape prokaryotic assemblages in submarine mud volcanoes.

    Science.gov (United States)

    Corinaldesi, Cinzia; Dell'Anno, Antonio; Danovaro, Roberto

    2012-06-01

    Mud volcanoes are geological structures in the oceans that have key roles in the functioning of the global ecosystem. Information on the dynamics of benthic viruses and their interactions with prokaryotes in mud volcano ecosystems is still completely lacking. We investigated the impact of viral infection on the mortality and assemblage structure of benthic prokaryotes of five mud volcanoes in the Mediterranean Sea. Mud volcano sediments promote high rates of viral production (1.65-7.89 × 10(9) viruses g(-1) d(-1)), viral-induced prokaryotic mortality (VIPM) (33% cells killed per day) and heterotrophic prokaryotic production (3.0-8.3 μgC g(-1) d(-1)) when compared with sediments outside the mud volcano area. The viral shunt (that is, the microbial biomass converted into dissolved organic matter as a result of viral infection, and thus diverted away from higher trophic levels) provides 49 mgC m(-2) d(-1), thus fuelling the metabolism of uninfected prokaryotes and contributing to the total C budget. Bacteria are the dominant components of prokaryotic assemblages in surface sediments of mud volcanoes, whereas archaea dominate the subsurface sediment layers. Multivariate multiple regression analyses show that prokaryotic assemblage composition is not only dependant on the geochemical features and processes of mud volcano ecosystems but also on synergistic interactions between bottom-up (that is, trophic resources) and top-down (that is, VIPM) controlling factors. Overall, these findings highlight the significant role of the viral shunt in sustaining the metabolism of prokaryotes and shaping their assemblage structure in mud volcano sediments, and they provide new clues for our understanding of the functioning of cold-seep ecosystems.

  14. Viral infections stimulate the metabolism and shape prokaryotic assemblages in submarine mud volcanoes

    Science.gov (United States)

    Corinaldesi, Cinzia; Dell'Anno, Antonio; Danovaro, Roberto

    2012-01-01

    Mud volcanoes are geological structures in the oceans that have key roles in the functioning of the global ecosystem. Information on the dynamics of benthic viruses and their interactions with prokaryotes in mud volcano ecosystems is still completely lacking. We investigated the impact of viral infection on the mortality and assemblage structure of benthic prokaryotes of five mud volcanoes in the Mediterranean Sea. Mud volcano sediments promote high rates of viral production (1.65–7.89 × 109 viruses g−1 d−1), viral-induced prokaryotic mortality (VIPM) (33% cells killed per day) and heterotrophic prokaryotic production (3.0–8.3 μgC g−1 d−1) when compared with sediments outside the mud volcano area. The viral shunt (that is, the microbial biomass converted into dissolved organic matter as a result of viral infection, and thus diverted away from higher trophic levels) provides 49 mgC m−2 d−1, thus fuelling the metabolism of uninfected prokaryotes and contributing to the total C budget. Bacteria are the dominant components of prokaryotic assemblages in surface sediments of mud volcanoes, whereas archaea dominate the subsurface sediment layers. Multivariate multiple regression analyses show that prokaryotic assemblage composition is not only dependant on the geochemical features and processes of mud volcano ecosystems but also on synergistic interactions between bottom-up (that is, trophic resources) and top-down (that is, VIPM) controlling factors. Overall, these findings highlight the significant role of the viral shunt in sustaining the metabolism of prokaryotes and shaping their assemblage structure in mud volcano sediments, and they provide new clues for our understanding of the functioning of cold-seep ecosystems. PMID:22170423

  15. Viral pneumonias: Typical and atypical findings

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff-Bleck, M.; Bleck, J.S.; Schirg, E.

    1987-10-01

    The clinical and radiological features of viral pneumonias are summarized and discussed. Although viral infections of the lung belong to atypical pneumonias they demonstrate not always the radiographic pattern of an interstitial pneumonia. Characteristic radiographic findings are quite rare. In most cases the microbial etiology cannot be predicted from chest radiographs. The appearance varies depending on the virulence of the organism and the resistence of the host. In this regard knowledge of epidemiological data as well as patients condition and underlying disease is of utmost importance. Differentiation between community- and hospital-acquired infection may be very helpful.

  16. Viral diseases in honey bee queens

    DEFF Research Database (Denmark)

    Francis, Roy Mathew

    Honey bees are important insects for human welfare, due to pollination as well as honey production. Viral diseases strongly impact honey bee health, especially since the spread of varroa mites. This dissertation deals with the interactions between honey bees, viruses and varroa mites. A new tool...... was developed to diagnose three viruses in honey bees. Quantitative PCR was used to investigate the distribution of two popular viruses in five different tissues of 86 honey bee queens. Seasonal variation of viral infection in honey bee workers and varroa mites were determined by sampling 23 colonies under...

  17. Structure of viral hepatitis in infants

    Directory of Open Access Journals (Sweden)

    T.V. Sorokman

    2017-07-01

    Full Text Available Background. Many current studies are devoted to the study of hepatitis caused by viral infections, which are qualified as TORCH-infection. In infants TORCH-induced lesions prevail in the structure of viral hepatitis, the largest proportion is hepatitis of cytomegalovirus etiology. The purpose was to study the structure of viral hepatitis in infants. Materials and methods. The study included sixty-two children (mean age 1.8 ± 0.9 years born in 2007–2016 treated in Chernivtsi Regional Children’s Clinical Hospital. The comparison group consisted of 36 healthy children of the same age. The pathogens of viral hepatitis B, C, TORCH infections were verified by enzyme immunoassay and polymerase chain reaction. The results of the research were analyzed using computer package Statistica StatSoft Inc. and Excel XP for Windows for a personal computer. Results. The results of the analysis of the liver diseases structure in 62 young children, according to hospital statistics, determined that the overwhelming majority (38 children; 61.3 % had viral hepatitis (VH, the other 24 (38.7 % patients were divided by the etiological structure of liver damage as follows: 8 (12.9 % patients had prolonged conjunctive jaundice, 7 (11.3 % patients had congenital metabolic disorders, 9 (14.5 % patients had congenital hepatobiliary abnomalities. 16.6 % of young children had hepatitis B and C viruses. In 5.8 % of cases VH was caused by viruses of the TORCH group of infections. Conclusions. In the structure of hepatobiliary diseases in infants, viral hepatitis (68.4 % is on the first ranked place. Among the viral hepatitis in children in the first year of life, CMV-hepatitis (68.4 % is most common, in children over 1 year old chronic hepatitis B and C. Severe obstetrical anamnesis, violations of pregnancy, placental infection are rather significant in the group of children with viral hepatitis. The main clinical signs of CMV-hepatitis are prolonged jaundice, cholestasis

  18. Latent Viral Marketing, Concepts and Control Methods

    OpenAIRE

    Sela, Alon; Goldenberg, Dmitri; Ben-Gal, Irad; Shmueli, Erez

    2017-01-01

    Numerus works that study the spread of information in social networks include a spreading mechanism in which a set of nodes is initially infected (i.e. seeded), followed by a viral process, which spontaneously spread the message through the nodes of the network. These models are used to describe the spread of rumors as well as the spread of new products and services. In reality however, it is quite rare that a product or service spreads through a social networks solely by viral forces. It is ...

  19. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...... by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...

  20. Persistence of foot-and mouth disease virus in ruminants

    DEFF Research Database (Denmark)

    Stenfeldt, Carolina; Belsham, Graham; Tjørnehøj, Kirsten

    During the spring of 2008, a new clinical project, with the aim of investigating mechanisms involved in development of FMD carrier animals, has been launched in the new FMD facilities of the Danish Veterinary Institute located at Lindholm Island. The project is based on a series of animal...... experiments, investigating the host response to FMD infection in sheep and cattle. FMD infection in ruminants involves initial viral replication in pharyngeal epithelia, from where the virus spreads systemically via the lymphatic system. Characteristic vesicular lesions develop in the cornified stratified...... In these locations, FMDV is capable of persistent replication, without being detected by the host cellular immune response, which would normally be expected to clear virus infected cells. In an ongoing series of experiments, animals of 4-5 moths of age are infected with FMD O UKG 34/2001, either through subepidermo...