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Sample records for herpes simplex encephalopathy

  1. Serum herpes simplex antibodies

    Science.gov (United States)

    ... 2. HSV-1 most often causes cold sores (oral herpes). HSV-2 causes genital herpes. How the Test ... whether a person has ever been infected with oral or genital herpes . It looks for antibodies to herpes simplex virus ...

  2. Recurrent zosteriform herpes simplex

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    Inamadar Arun

    1992-01-01

    Full Text Available A 25-year-old man had recurrent zosteriform herpes simplex for past 6 years. The attacks were precipitated by prolonged exposure to sunlight. Pain was mild and lesions used to subside each time in about 7 days. Clinical features which help in differentiating recurrent herpes simplex from recurrent herpes zoster are summarized.

  3. Epilepsy surgery for epileptic encephalopathy as a sequela of herpes simplex encephalitis: case report.

    Science.gov (United States)

    Taskin, Birce Dilge; Tanji, Kurenai; Feldstein, Neil A; McSwiggan-Hardin, Maureen; Akman, Cigdem I

    2017-07-01

    Herpes simplex virus (HSV) encephalitis can manifest with different clinical presentations, including acute monophasic illness and biphasic chronic granulomatous HSV encephalitis. Chronic encephalitis is much less common, and very rare late relapses are associated with intractable epilepsy and progressive neurological deficits with or without evidence of HSV in the cerebrospinal fluid. The authors report on an 8-year-old girl with a history of treated HSV-1 encephalitis when she was 13 months of age and focal epilepsy when she was 2 years old. Although free of clinical seizures, when she was 5, she experienced behavioral and academic dysfunction, which was later attributed to electrographic focal seizures and worsening electroencephalography (EEG) findings with electrical status epilepticus during slow-wave sleep (ESES). Following a right temporal lobectomy, chronic granulomatous encephalitis was diagnosed. The patient's clinical course improved with the resolution of seizures and EEG abnormalities.

  4. Human herpes simplex labialis.

    Science.gov (United States)

    Fatahzadeh, M; Schwartz, R A

    2007-11-01

    Humans are the natural host for eight of more than 80 known herpes viruses. Infections with herpes simplex virus type 1 (HSV-1) are ubiquitous worldwide and highly transmissible. Herpes simplex labialis (HSL) is the best-recognized recrudescent infection of the lips and perioral tissues caused by HSV-1. Facial lesions of HSL may be unsightly, frequent outbreaks unpleasant, and the infection itself more severe locally and systemically in immunocompromised people. This article highlights the pathogenesis, clinical presentation, diagnostic features and management issues for HSL.

  5. Herpes simplex-encefalitis

    DEFF Research Database (Denmark)

    Jørgensen, Laura Krogh; Mogensen, Trine Hyrup

    2017-01-01

    Herpes simplex encephalitis (HSE) is a rare disease, although it is the most common form of sporadic encephalitis worldwide. Recently, studies have provided important new insight into the genetic and immunological basis of HSE. However, even in the presence of antiviral treatment, mortality...

  6. Herpes Simplex Virus (Cold Sores)

    Science.gov (United States)

    ... Print Share Cold Sores in Children: About the Herpes Simplex Virus Page Content ​A child's toddler and ... Cold sores (also called fever blisters or oral herpes) start as small blisters that form around the ...

  7. Chronic herpes simplex virus encephalitis in childhood.

    NARCIS (Netherlands)

    Leen, W.G.; Weemaes, C.M.R.; Verbeek, M.M.; Willemsen, M.A.A.P.; Rotteveel, J.J.

    2006-01-01

    Although herpes simplex virus is a major cause of acute encephalitis in childhood, chronic herpes simplex virus encephalitis has only rarely been reported. This report presents a case of chronic herpes simplex virus encephalitis in a 6-year-old female. Diagnosis was based on the detection of herpes

  8. The Significance of Herpes Simplex for School Nurses

    Science.gov (United States)

    Ensor, Deirdre

    2005-01-01

    Herpes simplex is a common recurrent viral infection caused by the herpes simplex virus. The two closely related but distinct viruses that cause herpes simplex infections are herpes simplex 1 (HSV-1) and herpes simplex 2 (HSV-2). HSV-1 is commonly associated with infections around the oral mucosa and is the cause of herpes labialis, often referred…

  9. Neonatal Herpes Simplex Virus Infection.

    Science.gov (United States)

    James, Scott H; Kimberlin, David W

    2015-09-01

    Herpes simplex virus (HSV) 1 and HSV-2 infections are highly prevalent worldwide and are characterized by establishing lifelong infection with periods of latency interspersed with periodic episodes of reactivation. Acquisition of HSV by an infant during the peripartum or postpartum period results in neonatal HSV disease, a rare but significant infection that can be associated with severe morbidity and mortality, especially if there is dissemination or central nervous system involvement. Diagnostic and therapeutic advances have led to improvements in mortality and, to a lesser extent, neurodevelopmental outcomes, but room exists for further improvement. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Herpes simplex virus infection during pregnancy.

    Science.gov (United States)

    Stephenson-Famy, Alyssa; Gardella, Carolyn

    2014-12-01

    Genital herpes in pregnancy continues to cause significant maternal morbidity, with an increasing number of infections being due to oral-labial transmission of herpes simplex virus (HSV)-1. Near delivery, primary infections with HSV-1 or HSV-2 carry the highest risk of neonatal herpes infection, which is a rare but potentially devastating disease for otherwise healthy newborns. Prevention efforts have been limited by lack of an effective intervention for preventing primary infections and the unclear role of routine serologic testing.

  11. Prodrugs of herpes simplex thymidine kinase inhibitors.

    Science.gov (United States)

    Yanachkova, Milka; Xu, Wei-Chu; Dvoskin, Sofya; Dix, Edward J; Yanachkov, Ivan B; Focher, Federico; Savi, Lida; Sanchez, M Dulfary; Foster, Timothy P; Wright, George E

    2015-04-01

    Because guanine-based herpes simplex virus thymidine kinase inhibitors are not orally available, we synthesized various 6-deoxy prodrugs of these compounds and evaluated them with regard to solubility in water, oral bioavailability, and efficacy to prevent herpes simplex virus-1 reactivation from latency in a mouse model. Organic synthesis was used to prepare compounds, High Performance Liquid Chromatography (HPLC) to analyze hydrolytic conversion, Mass Spectrometry (MS) to measure oral bioavailability, and mouse latent infection and induced reactivation to evaluate the efficacy of a specific prodrug. Aqueous solubilities of prodrugs were improved, oxidation of prodrugs by animal cytosols occurred in vitro, and oral absorption of the optimal prodrug sacrovir™ (6-deoxy-mCF3PG) in the presence of the aqueous adjuvant Soluplus® and conversion to active compound N(2)-[3-(trifluoromethyl)pheny])guanine (mCF3PG) were accomplished in mice. Treatment of herpes simplex virus-1 latent mice with sacrovir™ in 1% Soluplus in drinking water significantly suppressed herpes simplex virus-1 reactivation and viral genomic replication. Ad libitum oral delivery of sacrovir™ was effective in suppressing herpes simplex virus-1 reactivation in ocularly infected latent mice as measured by the numbers of mice shedding infectious virus at the ocular surface, numbers of trigeminal ganglia positive for infectious virus, number of corneas that had detectable infectious virus, and herpes simplex virus-1 genome copy numbers in trigeminal ganglia following reactivation. These results demonstrate the statistically significant effect of the prodrug on suppressing herpes simplex virus-1 reactivation in vivo. © The Author(s) 2015.

  12. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Herpes simplex virus serological assays. 866.3305... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3305 Herpes simplex virus serological assays. (a) Identification. Herpes simplex virus serological assays are devices...

  13. Herpes simplex ulcerative esophagitis in healthy children

    Directory of Open Access Journals (Sweden)

    Abdulrahman A Al-Hussaini

    2011-01-01

    Full Text Available Herpes simplex virus is a common cause of ulcerative esophagitis in the immunocompromised or debilitated host. Despite a high prevalence of primary and recurrent Herpes simplex virus infection in the general population, Herpes simplex virus esophagitis (HSVE appears to be rare in the immunocompetent host. We report three cases of endoscopically-diagnosed HSVE in apparently immunocompetent children; the presentation was characterized by acute onset of fever, odynophagia, and dysphagia. In two cases, the diagnosis was confirmed histologically by identification of herpes viral inclusions and culture of the virus in the presence of inflammation. The third case was considered to have probable HSVE based on the presence of typical cold sore on his lip, typical endoscopic finding, histopathological evidence of inflammation in esophageal biopsies and positive serologic evidence of acute Herpes simplex virus infection. Two cases received an intravenous course of acyclovir and one had self-limited recovery. All three cases had normal immunological workup and excellent health on long-term follow-up.

  14. Antiviral drug resistance of herpes simplex virus

    NARCIS (Netherlands)

    Stranska, Ruzena

    2004-01-01

    Infections with herpes simplex virus (HSV) usually have an asymptomatic or benign course. However, severe infections do occur, particularly in HIV/AIDS patients or transplant recipients, and may be life-threatening unless adequate antiviral therapy is given. Since its introduction in the early 1980

  15. Early Diagnosis of Herpes Simplex Encephalitis

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    J Gordon Millichap

    2003-06-01

    Full Text Available Records of 38 patients, 23 boys and 15 girls (ages 3 months to 16 years [42% ages 3-12 months], seen between 1990 and 1997 with proven herpes simplex encephalitis (HSE, were reviewed retrospectively to determine the diagnostic reliability of polymerase chain reaction (PCR results, in a study at the Neuropediatric Service, Hopital Saint Vincent de Paul, Paris, France.

  16. Antiviral drug resistance of herpes simplex virus

    NARCIS (Netherlands)

    Stranska, Ruzena

    2004-01-01

    Infections with herpes simplex virus (HSV) usually have an asymptomatic or benign course. However, severe infections do occur, particularly in HIV/AIDS patients or transplant recipients, and may be life-threatening unless adequate antiviral therapy is given. Since its introduction in the early

  17. [Ocular hypertension in herpes simplex keratouveitis].

    Science.gov (United States)

    Burcea, M; Avram, Corina-Ioana; Stamate, Alina-Cristina; Malciolu, R; Oprea, S; Zemba, M

    2014-01-01

    The herpes simplex virus is one of the most common pathogens in humans, who are seropositive for the virus in 90% of the cases at the adult age. It determines reccurent infections in more than a third of the population and these infections depend on the immune response of the host. Ocular infections of newborns are due to the herpes simplex virus type 2, meanwhile type 1 is found predominantly at adults; almost all ocular structures can be affected. HSV-1 in the most frequent etiologic agent in infectious anterior uveitis (with the varicelo-zosterian virus) and it is responsible for 6-10% of all cases of anterior uveitis. More than half of the keratouveitides due to HSV will develop intraocular hypertension and open-angle secondary glaucoma, during reccurences and most of them will resolve after proper control of inflammation.

  18. Decompressive craniectomy in herpes simplex encephalitis

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    Muhammed Jasim Abdul Jalal

    2015-01-01

    Full Text Available Intracranial hypertension is a common cause of morbidity in herpes simplex encephalitis (HSE. HSE is the most common form of acute viral encephalitis. Hereby we report a case of HSE in which decompressive craniectomy was performed to treat refractory intracranial hypertension. A 32-year-old male presented with headache, vomiting, fever, and focal seizures involving the right upper limb. Cerebrospinal fluid-meningoencephalitic profile was positive for herpes simplex. Magnetic resonance image of the brain showed swollen and edematous right temporal lobe with increased signal in gray matter and subcortical white matter with loss of gray, white differentiation in T2-weighted sequences. Decompressive craniectomy was performed in view of refractory intracranial hypertension. Decompressive surgery for HSE with refractory hypertension can positively affect patient survival, with good outcomes in terms of cognitive functions.

  19. Development history of herpes simplex encephalitis

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    Jia-wei WANG

    2014-08-01

    Full Text Available Herpes simplex encephalitis (HSE is an acute central nervous system infection caused by herpes simplex virus (HSV. Early clinical manifestations mainly include fever, headache and unconsciousness; when progressing, psychiatric symptoms can occur. Death or serious neurological sequelae will happen if not treated. With the development of laboratory tests and imaging techniques, the early diagnosis of HSE is possible. Even though imaging with temporal lobe abnormal signal has the implication to HSE, the application of polymerase chain reaction (PCR in detecting HSV DNA in cerebrospinal fluid is currently the "gold standard" to diagnose HSE. Once diagnosed, acyclovir must be given as soon as possible, as delayed treatment will result in a poor outcome. doi: 10.3969/j.issn.1672-6731.2014.08.003

  20. A REVIEW ARTICLE ON HERPES SIMPLEX ENCEPHALITIS

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    A. Karimi MD

    2009-01-01

    Full Text Available Abstract:Herpes Simplex encephalitis (HSE is a life threatening outcome of Herpes simplex virus (HSV infection of the central nervous system (CNS. HSVaccounts for 2-5 percent of all cases of encephalitis. One third of cases occur in those younger than 20 years old and one half in those older than 50 years old.Clinical diagnosis is recommended in the encephalopathic, febrile patients with focal neurological signs. However, the clinical findings are not pathogonomic because numerous other diseases of CNS can mimic HSE. Diagnosis should be confirmed based on medical history, analysis of cerebrospinal fluid (CSF for protein and glucose contents, the cellular analysis and identifying the pathogens by serology and Polymerase Chain Reaction (PCR amplification .The diagnostic gold standard is the detection of HSV DNA in the cerebrospinal fluid by PCR. But negative results need to be interpreted regarding thepatients clinical signs and symptoms and the time of CSF sampling. Spike and slow wave patterns is observed in Electroencephalogram (EEG.Neuroimaging, especially Magnetic Resonance Imaging (MRI is essential for evaluating the patients, which shows temporal lobe edema or hemorrhage.All patients with HSE should be treated by intravenous Acyclovir (10mg/kg q8hr for 14-21 days. After completing therapy, PCR of the CSF can confirmthe elimination of replicating virus, assisting further management of the patient.Keywords:Herpes Simplex Virus (HSV, Encephalitis, Children

  1. Herpes simplex virus and the alimentary tract.

    Science.gov (United States)

    Lavery, Eric A; Coyle, Walter J

    2008-08-01

    Herpes simplex virus (HSV) infection is well known as a sexually transmitted disease. However, relatively little has been published concerning the presentations and treatment of HSV infection within the gastrointestinal tract, where HSV most commonly affects the esophagus in both immunocompromised and immunocompetent patients. HSV proctitis is not uncommon and occurs primarily in males having sex with males. In patients with normal immune systems, gastrointestinal HSV infections are generally self-limited and rarely require antiviral therapy. Treatment of infection is suggested for immunocompromised patients, though no large randomized controlled trials have been performed. This article reviews the manifestations of HSV infection within the luminal gastrointestinal tract and options for diagnosis and treatment.

  2. Interferon susceptibility of herpes simplex virus strains isolated from patients enrolled in clinical trials.

    OpenAIRE

    Armstrong, J. A.; Skicki-Mullen, M B; Breinig, M K; Ho, M

    1983-01-01

    Herpes simplex virus type 1 strains isolated from patients who had received interferon in a clinical trial were not more resistant to human leukocyte interferon than strains derived from recipients of a placebo. The susceptibility of herpes simplex virus type 2 strains isolated from herpes genitalis was slightly less than that of herpes simplex virus type 1 strains causing herpes genitalis.

  3. Pathogenesis of herpes simplex virus infections of the cornea

    NARCIS (Netherlands)

    J. Maertzdorf (Jeroen)

    2002-01-01

    textabstractThe identification of human herpes virus (HHV) infections can be traced back to ancient Greece where Herpes simplex vims (HSV) infections in humans were first documented. Hippocrates used the word "herpes", meaning to creep or crawl, to describe spreading skin lesions. Although the

  4. Herpes simplex virus infections of women and their offspring: implications for a developed society.

    OpenAIRE

    Whitley, R J

    1994-01-01

    Herpes simplex virus infections of humans have been known since ancient times. Contemporary society has witnessed a series of devastating manifestations of herpes simplex virus infections--namely, genital herpes simplex virus infection and neonatal herpes simplex virus infection. With the evolution of society, particularly advances in birth control and increasing promiscuity, the seroprevalence of herpes simplex virus type 2 infections has increased worldwide, however, more so in developed so...

  5. Herpes simplex virus encephalitis in hamadan, iran.

    Directory of Open Access Journals (Sweden)

    Masoud Sabouri Ghannad

    2013-09-01

    Full Text Available Encephalitis can cause a severe public health problem. The main aim of this research was to evaluate the medical laboratory results of patients with Herpes Simplex Virus (HSV encephalitis.Diagnosis of encephalitis for these patients was firstly based on a clinical profile for Herpes Simplex Encephalitis (HSE, plus either a detected HSV1&2-DNA by PCR in CSF or brain neuro-imaging results.Molecular testing on CSF showed that 15 patients (15% had HSV infection, 5 patients (5% had Varicella Zoster Virus (VZV and one case was positive for Human Immunodeficiency Virus (HIV-RNA in CSF. The cause of encephalitis in 79 out of 100 patients (79% was unknown. The comparison of CSF analysis in HSV positives and negatives showed a significant increase of glucose and protein levels in HSV positives than negatives. The mortality rate was 46.6% (7/15 in patients with HSV encephalitis compared to 11.4% (10/85 in non-HSV encephalitis (P = 0.003.In the current study, 15% of cases were diagnosed as having HSV.

  6. A REVIEW ARTICLE ON HERPES SIMPLEX ENCEPHALITIS

    Directory of Open Access Journals (Sweden)

    A. Karimi MD,

    2007-02-01

    Full Text Available Herpes Simplex encephalitis (HSE is a life threatening outcome of Herpes simplex virus (HSV infection of the central nervous system (CNS. HSVaccounts for 2-5 percent of all cases of encephalitis. One third of cases occur in those younger than 20 years old and one half in those older than 50 years old.Clinical diagnosis is recommended in the encephalopathic, febrile patients with focal neurological signs. However, the clinical findings are not pathogonomic because numerous other diseases of CNS can mimic HSE. Diagnosis should be confirmed based on medical history, analysis of cerebrospinal fluid (CSF for protein and glucose contents, the cellular analysis and identifying the pathogens by serology and Polymerase Chain Reaction (PCR amplification .The diagnostic gold standard is the detection of HSV DNA in the cerebrospinal fluid by PCR. But negative results need to be interpreted regarding thepatients clinical signs and symptoms and the time of CSF sampling. Spike and slow wave patterns is observed in Electroencephalogram (EEG.Neuroimaging, especially Magnetic Resonance Imaging (MRI is essential for evaluating the patients, which shows temporal lobe edema or hemorrhage.All patients with HSE should be treated by intravenous Acyclovir (10mg/kg q8hr for 14-21 days. After completing therapy, PCR of the CSF can confirmthe elimination of replicating virus, assisting further management of the patient.

  7. Reactivation of herpes simplex virus-1 following epilepsy surgery

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2015-01-01

    Conclusion: The authors stress the potential risk of reactivation of HSV encephalitis after intracranial surgery. Herpes simplex virus encephalitis must be considered in neurosurgical patients who develop postoperative seizures and fever.

  8. Oral shedding of herpes simplex virus type 2

    OpenAIRE

    Wald, A; Ericsson, M.; Krantz, E; Selke, S; Corey, L

    2004-01-01

    Objectives: Herpes simplex virus (HSV) 1 and HSV-2 reactivate preferentially in the oral and genital area, respectively. We aimed to define frequency and characteristics associated with oral shedding of HSV-2.

  9. EPIDEMIOLOGY OF THE HERPES SIMPLEX VIRUS INFECTION

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    Ljiljana Kostadinović

    2002-07-01

    Full Text Available Over 150 sorts of viruses are capable of causing diseases of the respiratory ways. The virus infections have become the cost to be paid for urbanization and industrialization. The acute virus infections jeopardize mankind by their complications with numerous consequences. They open up the way to super infections, they provoke endogenous infections and lead to insufficiency of the vital organs. The viruses penetrate the organism mainly through the respiratory ways, digestive and urinary-sexual organs and skin. Some viruses immediately at the place of their entrance into the organism find receptive cells in which they can multiply (herpes virus and etc.. Some viruses must get through the blood, through the lymph or the nerve fibers to the target organs that they have affinity for.The changes that primarily occur in the mouth with manifest lymphadenopathy of the surrounding area emerge with respect to the type of the acute infection dis-ease.The human herpes viruses are responsible for a great number of diseases in people; that is why it can be said that the infections they induce are a very frequent cause of people's diseases in the world. Man is natural and the only host for the types I and II of the herpes simplex virus (HSV; that is why the infected person is regarded as the source of infection. The infection transmission can be by direct contact or over the contaminated secretions during the sexual intercourse. The age and the socioeconomic status (living conditions, level of medical culture, habits, etc. affect to agreat extent epidemiology of the HSV infection. The HSV distribution in the region of Niš in the five-year period (from 1987 to 1992 was the highest in the early and late summer (June and September.

  10. Location and cloning of the herpes simplex virus type 2 thymidine kinase gene.

    OpenAIRE

    McDougall, J K; Masse, T H; Galloway, D A

    1980-01-01

    The herpes simplex virus type 2 thymidine kinase gene has been mapped to a position colinear with the herpes simplex virus type 1 thymidine kinase gene and cloned within a 4.0-kilobase fragment in pBR 322.

  11. Recidiverende erythema multiforme udløst af herpes simplex-virus

    DEFF Research Database (Denmark)

    Vestergård Grejsen, Dorthe; Henningsen, Emil

    2012-01-01

    We describe two cases of recurrent erythema multiforme, both associated to infection with herpes simplex virus. The importance of subclinical herpes is illustrated. Antiviral and additional treatment is described.......We describe two cases of recurrent erythema multiforme, both associated to infection with herpes simplex virus. The importance of subclinical herpes is illustrated. Antiviral and additional treatment is described....

  12. Disseminated Neonatal Herpes Caused by Herpes Simplex Virus Types 1 and 2

    Science.gov (United States)

    Martic, Jelena; Stanojevic, Maja; Jankovic, Sasa; Nedeljkovic, Jasminka; Nikolic, Ljubica; Pasic, Srdjan; Jankovic, Borisav; Jovanovic, Tanja

    2007-01-01

    Disseminated neonatal herpes simplex virus (HSV) infection is characterized by progressive multiple organ failure and high mortality rates. It can result from infection with either HSV-1 or HSV-2. We report a case of disseminated neonatal herpes that was caused by HSV-1 and HSV-2. PMID:17479897

  13. Chronic Ulcerative Herpes Simplex Virus Infection of the Vulva

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    Kelly Griffith-Bauer

    2012-09-01

    Full Text Available Herpes simplex virus infections in HIV-infected individuals can be clinically unusual and difficult to treat due to underlying problems with cell-mediated immunity and the occurrence of antiviral resistance. Additionally, partial or incomplete restoration of immune function may result in chronic ulcerations that require rotational treatments. In this report, we describe the case of a 38-year-old HIV-positive woman who developed the ulcerative form of chronic herpes simplex infection despite highly active antiretroviral therapy and valacyclovir prophylaxis. Repeated intravenous courses of foscarnet and topical cidofovir finally controlled her erosions as her cell-mediated immunity was slowly restored. This case highlights the challenges that still exist in diagnosing and managing this rare presentation of herpes simplex virus

  14. Pityriasis Lichenoides Chronica Associated with Herpes Simplex Virus Type 2

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    Antonio Javier González Rodríguez

    2012-01-01

    Full Text Available Introduction. Pityriasis lichenoides is a rare, acquired spectrum of skin conditions of an unknown etiology. Case Report. A 28-year-old man presented with recurrent outbreaks of herpes simplex virus associated with the onset of red-to-brown maculopapules located predominantly in trunk in each recurrence. Positive serologies to herpes simplex virus type 2 were detected. Histopathological examination of one of the lesions was consistent with a diagnosis of pityriasis lichenoides chronica. Discussion. Pityriasis lichenoides is a rare cutaneous entity of an unknown cause which includes different clinical presentations. A number of infectious agents have been implicated based on the clustering of multiple outbreaks and elevated serum titers to specific pathogens (human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, and herpes simplex virus. In our patient, resolution of cutaneous lesions coincided with the administration of antiviral drugs and clinical improvement in each genital herpes recurrence. In conclusion, we report a case in which cutaneous lesions of pityriasis lichenoides chronica and a herpes simplex virus-type 2-mediated disease have evolved concomitantly.

  15. Recurrent facial urticaria following herpes simplex labialis.

    Science.gov (United States)

    Zawar, Vijay; Godse, Kiran

    2012-03-01

    We describe recurrent acute right-sided facial urticaria associated with herpes labialis infection in a middle-aged female patient. Antiviral medications and antihistamines not only successfully cleared the herpes infection and urticaria but also prevented further recurrences.

  16. Recurrent facial urticaria following herpes simplex labialis

    OpenAIRE

    Vijay Zawar; Kiran Godse

    2012-01-01

    We describe recurrent acute right-sided facial urticaria associated with herpes labialis infection in a middle-aged female patient. Antiviral medications and antihistamines not only successfully cleared the herpes infection and urticaria but also prevented further recurrences.

  17. Zebrafish: modeling for herpes simplex virus infections.

    Science.gov (United States)

    Antoine, Thessicar Evadney; Jones, Kevin S; Dale, Rodney M; Shukla, Deepak; Tiwari, Vaibhav

    2014-02-01

    For many years, zebrafish have been the prototypical model for studies in developmental biology. In recent years, zebrafish has emerged as a powerful model system to study infectious diseases, including viral infections. Experiments conducted with herpes simplex virus type-1 in adult zebrafish or in embryo models are encouraging as they establish proof of concept with viral-host tropism and possible screening of antiviral compounds. In addition, the presence of human homologs of viral entry receptors in zebrafish such as 3-O sulfated heparan sulfate, nectins, and tumor necrosis factor receptor superfamily member 14-like receptor bring strong rationale for virologists to test their in vivo significance in viral entry in a zebrafish model and compare the structure-function basis of virus zebrafish receptor interaction for viral entry. On the other end, a zebrafish model is already being used for studying inflammation and angiogenesis, with or without genetic manipulations, and therefore can be exploited to study viral infection-associated pathologies. The major advantage with zebrafish is low cost, easy breeding and maintenance, rapid lifecycle, and a transparent nature, which allows visualizing dissemination of fluorescently labeled virus infection in real time either at a localized region or the whole body. Further, the availability of multiple transgenic lines that express fluorescently tagged immune cells for in vivo imaging of virus infected animals is extremely attractive. In addition, a fully developed immune system and potential for receptor-specific knockouts further advocate the use of zebrafish as a new tool to study viral infections. In this review, we focus on expanding the potential of zebrafish model system in understanding human infectious diseases and future benefits.

  18. Herpes simplex virus virion host shutoff function.

    Science.gov (United States)

    Kwong, A D; Kruper, J A; Frenkel, N

    1988-03-01

    Herpes simplex virus (HSV) virions contain one or more functions which mediate the shutoff of host protein synthesis and the degradation of host mRNA. HSV type 1 (HSV-1) mutants deficient in the virion shutoff of host protein synthesis (vhs mutants) were isolated and were found to be defective in their ability to degrade host mRNA. Furthermore, it was found that viral mRNAs in cells infected with the vhs 1 mutant have a significantly longer functional half-life than viral mRNAs in wild-type virus-infected cells. In the present study we have mapped the vhs1 mutation affecting the virion shutoff of host protein synthesis to a 265-base-pair NruI-XmaIII fragment spanning map coordinates 0.604 to 0.606 of the HSV-1 genome. The mutation(s) affecting the functional half-lives of host mRNA as well as the alpha (immediate-early), beta (early), and gamma (late) viral mRNAs were also mapped within this 265-base-pair fragment. Thus, the shutoff of host protein synthesis is most likely mediated by the same function which decreases the half-life of viral mRNA. The shorter half-life of infected-cell mRNAs may allow a more rapid modulation of viral gene expression in response to changes in the transcription of viral genes. Interestingly, the vhs1 mutation of HSV-1 maps within a region which overlaps the Bg/II-N sequences of HSV-2 DNA shown previously to transform cells in culture. The possible relationship between the transformation and host shutoff functions are discussed.

  19. Further Characterization of the UL37 Protein of Herpes Simplex Virus Type 1 and its Interaction with ICP8, the Major DNA-Binding Protein of Herpes Simplex Virus

    Science.gov (United States)

    1994-01-01

    Diseases Produced by Herpes Simplex Viruses Disease Gingivostomatitis Pha ryngotonsill itis Herpes labialis Genital herpes Primary (P) or Recurrent... herpes simplex labialis : experimental induction of lesions with UV light. J. Clin. Micro. 22:366-368. Stanberry, L.R. 1986. Herpesvirus latency and...UL37 Protein of Herpes Simplex Virus Type 1 and its Interaction with [CPS, the Major DNA~Binding Protein of Herpes Simplex Virus" beyond brief

  20. Herpes

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Herpes Testing Share this page: Was this page helpful? Also known as: Herpes Culture; Herpes Simplex Viral Culture; HSV DNA; HSV ...

  1. Unusual presentation of herpes simplex virus infection in a boxer: 'Boxing glove herpes'.

    Science.gov (United States)

    García-García, Begoña; Galache-Osuna, Cristina; Coto-Segura, Pablo; Suárez-Casado, Héctor; Mallo-García, Susana; Jiménez, Jorge Santos-Juanes

    2013-02-01

    Herein, we describe a patient with lesions of cutaneous herpes simplex virus 1 (HSV-1) infection over the knuckles of both hands in the context of an outbreak among boxers. Interestingly, the infection had an unusually long duration (4 weeks), and was not acquired directly through skin-to-skin contact, as it usually does among athletes (herpes gladiatorum). In our case, transmission was acquired through the use of shared boxing gloves contaminated by HSV-1. To the best of our knowledge, herpes gladiatorum, or wrestler's herpes, has not been described previously in boxers and infection over the knuckles is not commonly reported.

  2. On the mutation rate of herpes simplex virus type 1.

    Science.gov (United States)

    Drake, John W; Hwang, Charles B C

    2005-06-01

    All seven DNA-based microbes for which carefully established mutation rates and mutational spectra were previously available displayed a genomic mutation rate in the neighborhood of 0.003 per chromosome replication. The pathogenic mammalian DNA virus herpes simplex type 1 has an estimated genomic mutation rate compatible with that value.

  3. Genome Sequence of Herpes Simplex Virus 1 Strain SC16

    Science.gov (United States)

    Rastrojo, Alberto; López-Muñoz, Alberto Domingo

    2017-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1), also known as Human herpesvirus 1, is a highly prevalent human neurotropic pathogen that causes a variety of diseases, including lethal encephalitis. Here, we report the genome sequence of the HSV-1 strain SC16. PMID:28126930

  4. Computed tomography in young children with herpes simplex virus encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Sugimoto, T.; Woo, M.; Okazaki, H.; Nishida, N.; Hara, T.; Yasuhara, A.; Kasahara, M.; Kobayashi, Y.

    1985-09-01

    Computed tomographic (CT) scans were obtained from eight infants and young children with herpes simplex virus encephalitis. In two cases the initial scan showed diffuse edematous changes as a mass effect without laterality. Unilateral localized low attenuation in the initial scan was evident 4 days after the onset in one patient, and high attenuation in the initial scan appeared on the 6th day in another patient, but in general, it was not possible to establish an early diagnosis of herpes simplex virus encephalitis from CT scan. In the longitudinal study the calcification with ventriculomegaly appeared in 3 of 5 survivors, and gyriform calcification in 2 of 3 patients, respectively. The appearance of multicystic encephalomalacia was evident in one patient 6 months after the onset of neonatal herpes simplex encephalitis. It is shown that the CT findings of neonates and young children with herpes simplex encephalitis are different from those of older children and adults, and the importance of longitudinal CT studies was stressed in clarifying the pathophysiology of the central nervous system involvement in survivors.

  5. Recurrence of bilateral herpes simplex virus keratitis following bimatoprost use

    Directory of Open Access Journals (Sweden)

    Kothari Mihir

    2006-01-01

    Full Text Available A 76-year-old man presented with features of bilateral herpes simplex virus (HSV keratitis. It was found to be recurrence of bilateral HSV keratitis following the use of Bimatoprost eye drops for uncontrolled intraocular pressure in a case of bilateral primary open-angle glaucoma.

  6. The "Other" Venereal Diseases: Herpes Simplex, Trichomoniasis and Candidiasis.

    Science.gov (United States)

    McNab, Warren L.

    1979-01-01

    Although the term venereal disease has been synonymous with gonorrhea and syphilis, the Center for Disease Control now states that the number of new cases of herpes simplex, trichomoniasis, and candidiasis is rapidly approaching the number of cases of syphilis and gonorrhea. (MM)

  7. Herpes Simplex Mastitis: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Holly Brown

    1996-01-01

    Full Text Available The most common sites of herpes simplex virus (HSV infection are around the oral cavity and the genitalia. However, HSV can infect any skin or mucous membrane surface. One uncommon site of HSV infection is the breast. Reports of herpetic breast infections are predominantly cases of transmission from a systemically HSV-infected neonate to the mother during breast-feeding. A review of the literature identified only six reports suggesting HSV breast lesions acquired by means other than through an infected infant. Of these, only one report suggests HSV transmission to the breast from a male sexual partner. A second case of clinically unsuspected symptomatic herpes mastitis presumably acquired from sexual contact in a 46-year-old woman is presented. Herpes simplex type 1 was isolated by using polymerase chain reaction and restriction fragment length polymerization techniques. The purpose of this report is to alert physicians to HSV mastitis.

  8. Recurrent facial urticaria following herpes simplex labialis

    Directory of Open Access Journals (Sweden)

    Vijay Zawar

    2012-01-01

    Full Text Available We describe recurrent acute right-sided facial urticaria associated with herpes labialis infection in a middle-aged female patient. Antiviral medications and antihistamines not only successfully cleared the herpes infection and urticaria but also prevented further recurrences.

  9. Herpes Simplex Virus Infection Mimicking Bullous Disease in an Immunocompromised Patient

    Directory of Open Access Journals (Sweden)

    Anne L.Y. Lecluse

    2010-06-01

    Full Text Available Immunodeficient patients are at risk of developing extended or atypical herpes simplex virus infections, which can be easily misdiagnosed. We present the case of a 79-year-old, treatment-induced (oral corticosteroid, immunocompromised female with an extensive atypical herpes simplex virus infection. This patient presented with multiple erosions and vesicles on the trunk with a subacute onset. The clinical differential diagnosis was herpes simplex infection, herpes zoster infection, pemphigus vulgaris or bullous pemphigoid. Due to the atypical clinical presentation and negative Tzanck test, suspicion of viral infection was low. High-dose steroid treatment was initiated. Subsequent histopathology, however, showed a herpes simplex virus infection. After discontinuing steroid treatment and initiating antiviral treatment, the patient recovered within a week. Emphasis must be placed on the importance of clinical awareness of extended and clinically atypical herpes simplex infections in immunocompromised patients. A negative Tzanck test does not rule out the possibility of a herpes infection.

  10. Herpes Simplex Encephalitis of the Parietal Lobe: A Rare Presentation

    Science.gov (United States)

    Tkachenko, Lara; Moisi, Marc; Rostad, Steven; Umeh, Randle; Zwillman, Michael E; Tubbs, R. Shane; Page, Jeni; Newell, David W.; Delashaw, Johnny B

    2016-01-01

    A 69-year-old female with a history of breast cancer and hypertension presented with a rare case of herpes simplex encephalitis (HSE) isolated to her left parietal lobe. The patient’s first biopsy was negative for herpes simplex virus (HSV) I/II antigens, but less than two weeks later, the patient tested positive on repeat biopsy. This initial failure to detect the virus and the similarities between HSE and symptoms of intracranial hemorrhage (ICH) suggests repeat testing for HSV in the presence of ICH. Due to the frequency of patients with extra temporal HSE, a diagnosis of HSE should be more readily considered, particularly when a patient may not be improving and a concrete diagnosis has not been solidified. PMID:27774355

  11. Herpes Simplex Encephalitis of the Parietal Lobe: A Rare Presentation.

    Science.gov (United States)

    Fisahn, Christian; Tkachenko, Lara; Moisi, Marc; Rostad, Steven; Umeh, Randle; Zwillman, Michael E; Tubbs, R Shane; Page, Jeni; Newell, David W; Delashaw, Johnny B

    2016-09-16

    A 69-year-old female with a history of breast cancer and hypertension presented with a rare case of herpes simplex encephalitis (HSE) isolated to her left parietal lobe. The patient's first biopsy was negative for herpes simplex virus (HSV) I/II antigens, but less than two weeks later, the patient tested positive on repeat biopsy. This initial failure to detect the virus and the similarities between HSE and symptoms of intracranial hemorrhage (ICH) suggests repeat testing for HSV in the presence of ICH. Due to the frequency of patients with extra temporal HSE, a diagnosis of HSE should be more readily considered, particularly when a patient may not be improving and a concrete diagnosis has not been solidified.

  12. A rare cause of dysphagia: Herpes simplex esophagitis

    Institute of Scientific and Technical Information of China (English)

    Bee Lee; Grant Caddy

    2007-01-01

    Herpes simplex esophagitis (HSE) is well documented in immunosuppressed patients. However, it is rare in the immunocompetent host. We present a case of HSE in a 21 year-old healthy lady who was admitted to our unit with dysphagia, odynophagia and chest pAln. Clinical examination revealed mild epigastric tenderness and admission bloods including full blood picture, electrolytes and inflammatory markers were normal. She underwent an esophagogastroduodenoscopy (EGD) which revealed severe exudative, well-circumscribed ulcerations in her distal esophagus. Biopsies confirmed severe esophagitis with acute ulceration and subsequent polymerase chAln reaction (PCR) confirmed herpes simplex virus (HSV) type 1. Subsequent assessment fAlled to identify an immune disorder. HSE should be suspected when faced with characteristic endoscopic findings, even if the patient is immunocompetent. When the diagnosis of HSE is confirmed, an immune deficiency should be sought.

  13. Gerstmann's syndrome following an acute herpes simplex encephalitis.

    Science.gov (United States)

    Ilchevsky, S; Boev, I; Kazakova, T

    1998-01-01

    The authors present a rare clinical case of a woman who developed Gerstmann's syndrome following an acute Herpes simplex viral encephalitis. Clinical observation and laboratory evaluation were performed during the acute phase of the disease. After that the follow-up continued for one-year period. The localization of the pathologic process was determined by computerized tomography, conducted periodically. The characteristics of the clinical picture are interpreted in the context of the contemporary concepts of the topical diagnosis of Gerstmann's syndrome. The possibility of a sudden onset of acute Herpes simplex viral encephalitis without a preceding febrile-intoxication syndrome is worth noting. Conclusions are drawn stressing the need of an early etiologic treatment and the importance of the rehabilitation activities during the convalescence period.

  14. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Vafai, A.; Wellish, M.; Devlin, M.; Gilden, D.H. (Univ. of Colorado School of Medicine, Denver (USA)); Murray, R.S. (Univ. of Colorado School of Medicine, Denver (USA) Veterans Administration Medical Center, Denver, CO (USA))

    1988-04-01

    Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteins in human sensory ganglia.

  15. Is herpes simplex virus associated with peptic ulcer disease?

    OpenAIRE

    Löhr, J M; Nelson, J. A.; Oldstone, M B

    1990-01-01

    To test the hypothesis that herpes simplex virus type 1 (HSV-1) may be associated with peptic ulcer disease, we examined ulcerative lesions of the distal stomach and proximal duodenum for the presence of nucleic acids and antibodies specific for HSV-1. Utilizing in situ hybridization, immunocytochemistry, and polymerase chain reaction with sequencing, gastric or duodenal tissues from 4 of 22 patients (18%) with documented peptic ulcer disease demonstrated the presence of both specific HSV-1 n...

  16. Herpes simplex virus bronchiolitis in a cannabis user

    Science.gov (United States)

    Libraty, Daniel H.; Bocelli, Lisa; Fraire, Armando

    2013-01-01

    Herpes simplex virus (HSV) lower respiratory tract infections in adults are uncommon. We present a case of HSV bronchiolitis and pneumonitis in an immunocompetent individual, likely linked to chronic habitual marijuana use and a herpetic orolabial ulcer. The case serves as a reminder to consider HSV as a potential unusual cause of lower respiratory tract infection/inflammation in individuals with chronic habitual marijuana use. PMID:26912481

  17. Herpes Simplex Virus 1 Infection on a Reconstructive Free Flap

    OpenAIRE

    Parys, Simon P.; Leman, Thea; Gurfinkel, Reuven

    2013-01-01

    Objective: Herpes simplex virus 1 (HSV1) is a widespread virus that primarily causes orofacial infection. Methods: We present a case of HSV1 infection on a free radial forearm flap used to reconstruct a palate defect. Initially, the free flap appeared healthy; however, after 48 hours the free flap appeared in distress, with dark red colour and fast capillary refill. Venous congestion was suspected, and the patient underwent a second operation where no vascular compromise was found. Vesicles w...

  18. Herpes simplex virus bronchiolitis in a cannabis user

    Directory of Open Access Journals (Sweden)

    Daniel H. Libraty

    2014-01-01

    Full Text Available Herpes simplex virus (HSV lower respiratory tract infections in adults are uncommon. We present a case of HSV bronchiolitis and pneumonitis in an immunocompetent individual, likely linked to chronic habitual marijuana use and a herpetic orolabial ulcer. The case serves as a reminder to consider HSV as a potential unusual cause of lower respiratory tract infection/inflammation in individuals with chronic habitual marijuana use.

  19. Herpes simplex virus bronchiolitis in a cannabis user

    OpenAIRE

    Daniel H Libraty; Lisa Bocelli; Armando Fraire

    2013-01-01

    Herpes simplex virus (HSV) lower respiratory tract infections in adults are uncommon. We present a case of HSV bronchiolitis and pneumonitis in an immunocompetent individual, likely linked to chronic habitual marijuana use and a herpetic orolabial ulcer. The case serves as a reminder to consider HSV as a potential unusual cause of lower respiratory tract infection/inflammation in individuals with chronic habitual marijuana use.

  20. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome mimicking herpes simplex encephalitis on imaging studies.

    Science.gov (United States)

    Gieraerts, Christopher; Demaerel, Philippe; Van Damme, Philip; Wilms, Guido

    2013-01-01

    We present a case in which mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome mimicked the clinical and radiological signs of herpes simplex encephalitis. In a patient with subacute encephalopathy, on computed tomography and magnetic resonance imaging, lesions were present in both temporal lobes extending to both insular regions with sparing of the lentiform nuclei and in both posterior straight and cingulate gyri. Final diagnosis of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome was based on biochemical investigations on cerebrospinal fluid, electromyogram, muscle biopsy, and genetic analysis. On diffusion-weighted imaging, diffusion restriction was present in some parts of the lesions but not throughout the entire lesions. We suggest that this could be an important sign in the differential diagnosis with herpes simplex encephalitis.

  1. Evolutionary origins of human herpes simplex viruses 1 and 2.

    Science.gov (United States)

    Wertheim, Joel O; Smith, Martin D; Smith, Davey M; Scheffler, Konrad; Kosakovsky Pond, Sergei L

    2014-09-01

    Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years. The primate simplex viruses exemplify this pattern of virus-host codivergence, at a minimum, as far back as the most recent common ancestor of New World monkeys, Old World monkeys, and apes. Humans are the only primate species known to be infected with two distinct herpes simplex viruses: HSV-1 and HSV-2. Human herpes simplex viruses are ubiquitous, with over two-thirds of the human population infected by at least one virus. Here, we investigated whether the additional human simplex virus is the result of ancient viral lineage duplication or cross-species transmission. We found that standard phylogenetic models of nucleotide substitution are inadequate for distinguishing among these competing hypotheses; the extent of synonymous substitutions causes a substantial underestimation of the lengths of some of the branches in the phylogeny, consistent with observations in other viruses (e.g., avian influenza, Ebola, and coronaviruses). To more accurately estimate ancient viral divergence times, we applied a branch-site random effects likelihood model of molecular evolution that allows the strength of natural selection to vary across both the viral phylogeny and the gene alignment. This selection-informed model favored a scenario in which HSV-1 is the result of ancient codivergence and HSV-2 arose from a cross-species transmission event from the ancestor of modern chimpanzees to an extinct Homo precursor of modern humans, around 1.6 Ma. These results provide a new framework for understanding human herpes simplex virus evolution and demonstrate the importance of using selection-informed models of sequence evolution when investigating viral origin hypotheses.

  2. Seronegative Herpes simplex Associated Esophagogastric Ulcer after Liver Transplantation

    Science.gov (United States)

    Matevossian, Edouard; Doll, Dietrich; Weirich, Gregor; Burian, Maria; Knebel, Carolin; Thorban, Stefan; Hüser, Norbert

    2008-01-01

    Herpes simplex infection is characterized by acute or subacute infection, often followed by a chronic carrier state. Consecutive recurrences may flare up if immunocompromise occurs. Herpes simplex associated esophagitis or duodenal ulcer have been reported in immunocompromised patients due to neoplasm, HIV/AIDS or therapeutically induced immune deficiency. Here we report the case of an HSV-DNA seronegative patient who developed grade III dysphagia 13 days after allogeneic liver transplantation. Endoscopy revealed an esophageal-gastric ulcer, and biopsy histopathology showed a distinct fibroplastic and capillary ulcer pattern highly suspicious for viral infection. Immunohistochemistry staining revealed a distinct nuclear positive anti-HSV reaction. Antiviral therapy with acyclovir and high-dose PPI led to a complete revision of clinical symptoms within 48 h. Repeat control endoscopy after 7 days showed complete healing of the former ulcer site at the gastroesophageal junction. Although the incidence of post-transplantation Herpes simplex induced gastroesophageal disease is low, the viral HSV ulcer may be included into a differential diagnosis if dysphagia occurs after transplantation even if HSV-DNA PCR is negative. PMID:21490847

  3. Seronegative Herpes simplex Associated Esophagogastric Ulcer after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Edouard Matevossian

    2008-03-01

    Full Text Available Herpes simplex infection is characterized by acute or subacute infection, often followed by a chronic carrier state. Consecutive recurrences may flare up if immunocompromise occurs. Herpes simplex associated esophagitis or duodenal ulcer have been reported in immunocompromised patients due to neoplasm, HIV/AIDS or therapeutically induced immune deficiency. Here we report the case of an HSV-DNA seronegative patient who developed grade III dysphagia 13 days after allogeneic liver transplantation. Endoscopy revealed an esophageal-gastric ulcer, and biopsy histopathology showed a distinct fibroplastic and capillary ulcer pattern highly suspicious for viral infection. Immunohistochemistry staining revealed a distinct nuclear positive anti-HSV reaction. Antiviral therapy with acyclovir and high-dose PPI led to a complete revision of clinical symptoms within 48 h. Repeat control endoscopy after 7 days showed complete healing of the former ulcer site at the gastroesophageal junction. Although the incidence of post-transplantation Herpes simplex induced gastroesophageal disease is low, the viral HSV ulcer may be included into a differential diagnosis if dysphagia occurs after transplantation even if HSV-DNA PCR is negative.

  4. Prevalence of intrathecal acyclovir resistant virus in herpes simplex encephalitis patients

    NARCIS (Netherlands)

    J.G. Mitterreiter (Johanna G.); M.J. Titulaer (Maarten); G.P. van Nierop (Gijsbert); J.J.A. van Kampen (Jeroen); G.I. Aron; A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George); W.J.D. Ouwendijk (Werner )

    2016-01-01

    textabstractHerpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted

  5. Prevalence of intrathecal acyclovir resistant virus in herpes simplex encephalitis patients

    NARCIS (Netherlands)

    J.G. Mitterreiter (Johanna G.); M.J. Titulaer (Maarten); G.P. van Nierop (Gijsbert); J.J.A. van Kampen (Jeroen); G.I. Aron; A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George); W.J.D. Ouwendijk (Werner )

    2016-01-01

    textabstractHerpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted

  6. Neonatal herpes simplex virus infection: epidemiology and treatment.

    Science.gov (United States)

    James, Scott H; Kimberlin, David W

    2015-03-01

    Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are highly prevalent viruses capable of establishing lifelong infection. Genital herpes in women of childbearing age represents a major risk for mother-to-child transmission (MTCT) of HSV infection, with primary and first-episode genital HSV infections posing the highest risk. The advent of antiviral therapy with parenteral acyclovir has led to significant improvement in neonatal HSV disease mortality. Further studies are needed to improve the clinician's ability to identify infants at increased risk for HSV infection and prevent MTCT, and to develop novel antiviral agents with increased efficacy in infants with HSV infection. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Herpes Simplex Virus-2 Esophagitis in a Young Immunocompetent Adult

    Directory of Open Access Journals (Sweden)

    Deepak K. Kadayakkara

    2016-01-01

    Full Text Available Herpes simplex esophagitis (HSE is commonly identified in immunosuppressed patients. It is rare among immunocompetent patients and almost all of the reported cases are due to HSV-1 infection. HSV-2 esophagitis is extremely rare. We report the case of a young immunocompetent male who presented with dysphagia, odynophagia, and epigastric pain. Endoscopy showed multitudes of white nummular lesions in the distal esophagus initially suspected to be candida esophagitis. However, classic histopathological findings of multinucleated giant cells with eosinophilic intranuclear inclusions and positive HSV-2 IgM confirmed the diagnosis of HSV-2 esophagitis. The patient rapidly responded to acyclovir treatment. Although HSV-2 is predominantly associated with genital herpes, it can cause infections in other parts of the body previously attributed to only HSV-1 infection.

  8. Inhibitors of Nucleotidyltransferase Superfamily Enzymes Suppress Herpes Simplex Virus Replication

    OpenAIRE

    2014-01-01

    Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 μM, with suppression at 50 μM reaching ∼1 million-fold. Five...

  9. Case report: symptomatic oral herpes simplex virus type 2 and asymptomatic genital shedding.

    Science.gov (United States)

    Olin, Laura; Wald, Anna

    2006-05-01

    A 42-year-old bisexual man with a history of recurrent oral herpes and no history of genital herpes was noted to have antibody to herpes simplex virus type 2 (HSV-2) only. During a symptomatic oral recurrence, HSV-2 was found in a perioral lesion as well as in the genital area.

  10. Charles Bonnet syndrome after herpes simplex encephalitis.

    Science.gov (United States)

    Aydin, Ömer Faruk; Ince, Hülya; Taşdemir, Haydar Ali; Özyürek, Hamit

    2012-04-01

    Visual impairment associated with Charles Bonnet syndrome is rarely reported in childhood. We describe a child who presented with visual hallucinations and postinfectious bilateral retrobulbar optic neuritis. The patient had undergone acyclovir therapy for 3 weeks because of herpes encephalitis. Four days after therapy was completed, he experienced visual impairment in both eyes. He manifested a bilateral decrease in visual acuity, with normal funduscopic findings. The patient experienced visual hallucinations for about 1 week, and then experienced total loss of vision. During his hallucinations, the patient did not exhibit behavioral changes or cognitive impairment. The visual hallucinations included unfamiliar children hiding under his bed, and he spoke to someone whom he did not know. Magnetic resonance imaging indicated bilateral optic nerve hyperintensity on T(2)-weighted and contrast-enhanced images. The patient received corticosteroid therapy for his retrobulbar optic neuritis, and his vision returned to normal after 1 month. Although rare, visual impairment can be associated with complex visual hallucinations indicative of Charles Bonnet syndrome.

  11. Empiric acyclovir for neonatal herpes simplex virus infection.

    Science.gov (United States)

    Vanderpluym, Christina; Tawfik, Gerda; Hervas-Malo, Marilou; Lacaze-Masmonteil, Thierry; Kellner, James; Robinson, Joan L

    2012-08-01

    Because neonatal herpes simplex virus (NHSV) infection is difficult to diagnose, there has been a move towards using more empiric acyclovir (ACV). The purpose of this study was to review the use of ACV to optimize future management of NHSV. Charts were reviewed for infants started on intravenous ACV up to day 43 of life--January 2001 through February 2007--at five hospitals in Edmonton and Calgary. ACV was started for possible (N = 115) or proven (N = 3) herpes simplex virus (HSV) infection. Six of the infants with possible HSV infection later had proven HSV infection. Seizures (34%), hemodynamic instability (29%) and skin lesions (24%) were the most common indications for ACV. Among the 118 infants, 106 (90%) had cerebrospinal fluid obtained and 82 (69%) had at least one surface swab for HSV but 4 (3%) had no specimens submitted for HSV detection. ACV was continued for 3.9 ± 3.5 days in the infants with no proven HSV disease. Possible nephrotoxicity from ACV was recorded in 3 of these 109 infants and in none of the infants with proven HSV disease. Clinicians in Alberta primarily consider the diagnosis of NHSV infection when confronted with a neonate with seizures, hemodynamic instability or suspicious skin lesions, but need to consider the diagnosis more often if all cases are to be treated at first presentation. They often perform incomplete investigations to rule out NHSV infection. Adverse events from ACV appear to be uncommon when the drug is used for suspected NHSV disease.

  12. Herpes simplex virus 1 pneumonia: conventional chest radiograph pattern

    Energy Technology Data Exchange (ETDEWEB)

    Umans, U.; Golding, R.P.; Duraku, S.; Manoliu, R.A. [Dept. of Radiology, Academic Hospital ' ' Vrije Universiteit' ' , Amsterdam (Netherlands)

    2001-06-01

    The aim of this study was to describe the findings on plain chest radiographs in patients with herpes simplex virus pneumonia (HSVP). The study was based on 17 patients who at a retrospective search have been found to have a monoinfection with herpes simplex virus. The diagnosis was established by isolation of the virus from material obtained during fiberoptic bronchoscopy (FOB) which also included broncho-alveolar lavage and tissue sampling. Fourteen patients had a chest radiograph performed within 24 h of the date of the FOB. Two radiographs showed no abnormalities of the lung parenchyma. The radiographs of the other 12 patients showed lung opacification, predominantly lobar or more extensive and always bilateral. Most patients presented with a mixed airspace and interstitial pattern of opacities, but 11 of 14 showed at least an airspace consolidation. Lobar, segmental, or subsegmental atelectasis was present in 7 patients, and unilateral or bilateral pleural effusion in 8 patients, but only in 1 patient was it a large amount. In contradiction to the literature which reports a high correlation between HSVP and acute respiratory distress syndrome (ARDS), 11 of 14 patients did not meet the pathophysiological criteria for ARDS. The radiologist may suggest the diagnosis of HSVP when bilateral airspace consolidation or mixed opacities appear in a susceptible group of patients who are not thought to have ARDS or pulmonary edema. The definite diagnosis of HSV pneumonia can be established only on the basis of culture of material obtained by broncho-alveolar lavage. (orig.)

  13. Unusual initial presentation of herpes simplex virus as inguinal lymphadenopathy.

    Science.gov (United States)

    Fleming, Sarah A; Strickler, John G

    2015-01-01

    Genital herpes simplex virus (HSV) infections are a common cause of inguinal lymphadenopathy. However, surgical excision of enlarged inguinal nodes is almost never performed to initially diagnose genital herpes simplex virus, due to the distinct external presentation of genital herpetic vesicles that usually occur with the first symptoms of infection. Therefore, the histologic and immunophenotypic features of HSV-associated inguinal lymphadenopathy are unfamiliar to most pathologists. The current report describes the lymph node pathology of two immunocompetent patients, whose initial HSV diagnosis was established through surgical excision of enlarged inguinal lymph nodes. Histologic examination showed features consistent with viral lymphadenopathy, including florid follicular hyperplasia, monocytoid B-cell hyperplasia, and paracortical hyperplasia without extensive necrosis. Immunohistochemical stains for HSV antigens, using polyclonal anti-HSV I and II antibodies, demonstrate strong immunoreactivity for HSV in a small number of cells in the subcapsular sinuses, especially in areas with monocytoid B-cell hyperplasia. Rare scattered HSV-positive cells also are identified in paracortical areas and germinal centers. We conclude that an initial diagnosis of genital HSV infection may be established by inguinal lymph node biopsy.

  14. Unusual Initial Presentation of Herpes Simplex Virus as Inguinal Lymphadenopathy

    Directory of Open Access Journals (Sweden)

    Sarah A. Fleming

    2015-01-01

    Full Text Available Genital herpes simplex virus (HSV infections are a common cause of inguinal lymphadenopathy. However, surgical excision of enlarged inguinal nodes is almost never performed to initially diagnose genital herpes simplex virus, due to the distinct external presentation of genital herpetic vesicles that usually occur with the first symptoms of infection. Therefore, the histologic and immunophenotypic features of HSV-associated inguinal lymphadenopathy are unfamiliar to most pathologists. The current report describes the lymph node pathology of two immunocompetent patients, whose initial HSV diagnosis was established through surgical excision of enlarged inguinal lymph nodes. Histologic examination showed features consistent with viral lymphadenopathy, including florid follicular hyperplasia, monocytoid B-cell hyperplasia, and paracortical hyperplasia without extensive necrosis. Immunohistochemical stains for HSV antigens, using polyclonal anti-HSV I and II antibodies, demonstrate strong immunoreactivity for HSV in a small number of cells in the subcapsular sinuses, especially in areas with monocytoid B-cell hyperplasia. Rare scattered HSV-positive cells also are identified in paracortical areas and germinal centers. We conclude that an initial diagnosis of genital HSV infection may be established by inguinal lymph node biopsy.

  15. Concomitant herpes simplex virus colitis and hepatitis in a man with ulcerative colitis

    Science.gov (United States)

    Phadke, Varun K.; Friedman-Moraco, Rachel J.; Quigley, Brian C.; Farris, Alton B.; Norvell, J. P.

    2016-01-01

    Abstract Background: Herpesvirus infections often complicate the clinical course of patients with inflammatory bowel disease; however, invasive disease due to herpes simplex virus is distinctly uncommon. Methods: We present a case of herpes simplex virus colitis and hepatitis, review all the previously published cases of herpes simplex virus colitis, and discuss common clinical features and outcomes. We also discuss the epidemiology, clinical manifestations, diagnosis, and management of herpes simplex virus infections, focusing specifically on patients with inflammatory bowel disease. Results: A 43-year-old man with ulcerative colitis, previously controlled with an oral 5-aminosalicylic agent, developed symptoms of a colitis flare that did not respond to treatment with systemic corticosteroid therapy. One week later he developed orolabial ulcers and progressive hepatic dysfunction, with markedly elevated transaminases and coagulopathy. He underwent emergent total colectomy when imaging suggested bowel micro-perforation. Pathology from both the colon and liver was consistent with herpes simplex virus infection, and a viral culture of his orolabial lesions and a serum polymerase chain reaction assay also identified herpes simplex virus. He was treated with systemic antiviral therapy and made a complete recovery. Conclusions: Disseminated herpes simplex virus infection with concomitant involvement of the colon and liver has been reported only 3 times in the published literature, and to our knowledge this is the first such case in a patient with inflammatory bowel disease. The risk of invasive herpes simplex virus infections increases with some, but not all immunomodulatory therapies. Optimal management of herpes simplex virus in patients with inflammatory bowel disease includes targeted prophylactic therapy for patients with evidence of latent infection, and timely initiation of antiviral therapy for those patients suspected to have invasive disease. PMID:27759636

  16. Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

    Science.gov (United States)

    Chentoufi, Aziz Alami; BenMohamed, Lbachir

    2012-01-01

    Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In the majority of cases, herpes infections are clinically asymptomatic. However, in symptomatic individuals, the latent HSV can spontaneously and frequently reactivate, reinfecting the muco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed. PMID:23320014

  17. Diffusion-weighted MR imaging findings in a patient with herpes simplex encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Heiner, L. E-mail: heiner_lajos@freemail.hu; Demaerel, Ph

    2003-03-01

    Introduction: Herpes simplex meningoencephalitis is one of the most common viral central nervous system infection in adults. Early diagnosis is essential for treatment. Case report: We present a case of a 68-year-old female patient with herpes simplex infection. On admission, she was in severe clinical condition. Diffusion-weighted (DW) magnetic resonance imaging detected brain involvement better than conventional sequences. After acyclovir therapy, the patient fully recovered. Conclusion: DW magnetic resonance imaging is expected to provide a more sensitive imaging in herpes simplex patients than conventional sequences.

  18. Clinical and biological differences between recurrent herpes simplex virus and varicella-zoster virus infections

    Energy Technology Data Exchange (ETDEWEB)

    Straus, S.E. (National Institute of Allergy and Infectious Diseases, Bethesda, MD (USA))

    1989-12-01

    The major features that distinguish recurrent herpes simplex virus infections from zoster are illustrated in this article by two case histories. The clinical and epidemiologic features that characterize recurrent herpes simplex virus and varicella-zoster virus infections are reviewed. It is noted that herpesvirus infections are more common and severe in patients with cellular immune deficiency. Each virus evokes both humoral and cellular immune response in the course of primary infection. DNA hybridization studies with RNA probes labelled with sulfur-35 indicate that herpes simplex viruses persist within neurons, and that varicella-zoster virus is found in the satellite cells that encircle the neurons.

  19. Clinical characteristics of hypertrophic herpes simplex genitalis and treatment outcomes of imiquimod: a retrospective observational study

    Directory of Open Access Journals (Sweden)

    Charussri Leeyaphan

    2015-04-01

    Conclusions: Atypical manifestations of herpes simplex genitalis require careful consideration because their frequency is rising, particularly in patients with HIV infection. Although acyclovir is important in their treatment, imiquimod provides an additional benefit in resistant cases.

  20. Case of herpes simplex encephalitis (HSE) with characteristic CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Imamura, Shigehiro (Kumamoto Rosai Hospital (Japan)); Nakayama, Toshio; Yamanaga, Hiroaki; Nakanishi, Ryoji; Ideta, Tooru

    1984-01-01

    CT scans of a 59-year-old woman, with serologically comfirmed herpes simplex encephalitis (HSE) were studied sequentially from 9 days after onset. The initial findings in CT scan were low density areas in insular cortex, claustrum and hippocampus. The low density areas, then, spread to the temporal lobe, rectal and cingulate gyri and occipital lobe, according to clinical progression of the disease. However, these low density areas disappeared and changed into isodensity areas in 25-35 days after oneset, which then returned to low density areas again in 51 days after onset. Thes characteristic phenomenon resembled a ''fogging effect,'' which is frequently seen during the second or third week after onset of ischemic cerebral infarction. HSE is characterized pathologically by acute hemorrhagic necrotizing encephalitis. Though cerebral angiography was not performed in this case, these characteristic CT findings suggested that HSE may have been associated with vascular involvement.

  1. New strategies against drug resistance to herpes simplex virus

    Science.gov (United States)

    Jiang, Yu-Chen; Feng, Hui; Lin, Yu-Chun; Guo, Xiu-Rong

    2016-01-01

    Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV. PMID:27025259

  2. UV radiation and mouse models of herpes simplex virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Norval, Mary; El-Ghorr, A.A. [Edinburgh Univ. Medical School (United Kingdom). Dept. of Medical Microbiology

    1996-08-01

    Orolabial human infections with herpes simplex virus type 1 (HSV-1) are very common; following the primary epidermal infection, the virus is retained in a latent form in the trigeminal ganglia from where it can reactivate and cause a recrudescent lesion. Recrudescences are triggered by various stimuli including exposure to sunlight. In this review three categories of mouse models are used to examine the effects of UV irradiation on HSV infections: these are UV exposure prior to primary infection, UV exposure as a triggering event for recrudescence and UV exposure prior to challenge with virus is mice already immunized to HSV. In each of these models immunosuppression occurs, which is manifest, in some instances, in increased morbidity or an increased rate of recrudescence. Where known, the immunological mechanisms involved in the models are summarized and their relevance to human infections considered. (Author).

  3. The miRNAs of Herpes Simplex Virus (HSV)

    Institute of Scientific and Technical Information of China (English)

    Le Sun; Qihan Li

    2012-01-01

    Herpes simplex virus (HSV) is a group of common human pathogens with two serotypes HSV-1 and HSV-2.The prevalence of HSV is worldwide.It primarily infects humans through epithelial cells,when it introduces a latent infection into the nervous system.During viral latency,only a region known as the latency-associated transcript (LAT) is expressed.The discovery of HSV miRNAs helps to draw a larger picture of the infection and pathogenesis of the virus.This review summarizes miRNAs found in HSV-1 and HSV-2 so far.The functional studies of miRNAs in HSV to date indicate that they play a stage-specific role coordinated with viral proteins to maintain the virus life cycle.

  4. Herpes Simplex Viruses and Induction of Interferon Responses

    Institute of Scientific and Technical Information of China (English)

    Yijie Ma; Dustin Vepooten; Bin He

    2008-01-01

    Herpes simplex viruses (HSV) are human pathogens responsible for a variety of diseases,including localized mucocutaneous lesions,encephalitis,and disseminated diseases.HSV infection leads to rapid induction of innate immune responses.A critical part of this host response is the type I IFN system including the induction of type I IFNs,IFN-mediated signaling and amplification of IFN response.This provides the host with immediate countermeasure during acute infection to limit initial viral replication and to facilitate an appropriate adaptive immune response.However,HSV has devised multiple strategies to evade and interfere with innate immunity.This review will focus on the induction of type I IFN response by HSV during acute infection and current knowledge of mechanisms by which HSV interferes with this induction process.

  5. [Role of Herpes simplex virus in the immune stromal keratitis].

    Science.gov (United States)

    Vinagre, C; Martínez, M J; Vogel, M; Traipe, L; Stoppel, J; Squella, O; Srur, M; Charlín, R

    2001-03-01

    Herpes simplex virus (HSV) infection of the cornea is a leading cause of blindness in occidental countries and a common recurrent manifestation of it is the immune stromal keratitis (ISK). However, it is not known whether active viral replication occurs during the acute phase of the disease, because isolation of the virus by conventional culture techniques has not been accomplished. To establish the presence of HSV in patients with ISK. Fourteen corneal swabbing samples, from active diseased eyes of patients with clinical diagnosis of ISK, were submitted to Herpchek and PCR for the identification of HSV antigens and genome. All ISK samples were negative by both techniques. It was not possible to identify HSV antigens nor their genome by the methodology used. It is likely that, they can't be detected in corneal superficial layers or probably there is no viral replication at this stage of the disease, so antiviral therapy should be reconsidered.

  6. New strategies against drug resistance to herpes simplex virus

    Institute of Scientific and Technical Information of China (English)

    Yu-Chen Jiang; Hui Feng; Yu-Chun Lin; Xiu-Rong Guo

    2016-01-01

    Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV.

  7. Herpes simplex virus 1 induces de novo phospholipid synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Sutter, Esther [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Oliveira, Anna Paula de; Tobler, Kurt [Electron microscopy, Institute of Virology, University of Zuerich (Switzerland); Schraner, Elisabeth M. [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Sonda, Sabrina [Institute of Parasitology, University of Zuerich (Switzerland); Kaech, Andres [Center for Microscopy and Image Analysis, University of Zuerich (Switzerland); Lucas, Miriam S. [Electron Microscopy ETH Zuerich (EMEZ), Swiss Federal Institute of Technology, Zuerich (Switzerland); Ackermann, Mathias [Electron microscopy, Institute of Virology, University of Zuerich (Switzerland); Wild, Peter, E-mail: pewild@access.uzh.ch [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland)

    2012-08-01

    Herpes simplex virus type 1 capsids bud at nuclear membranes and Golgi membranes acquiring an envelope composed of phospholipids. Hence, we measured incorporation of phospholipid precursors into these membranes, and quantified changes in size of cellular compartments by morphometric analysis. Incorporation of [{sup 3}H]-choline into both nuclear and cytoplasmic membranes was significantly enhanced upon infection. [{sup 3}H]-choline was also part of isolated virions even grown in the presence of brefeldin A. Nuclei expanded early in infection. The Golgi complex and vacuoles increased substantially whereas the endoplasmic reticulum enlarged only temporarily. The data suggest that HSV-1 stimulates phospholipid synthesis, and that de novo synthesized phospholipids are inserted into nuclear and cytoplasmic membranes to i) maintain membrane integrity in the course of nuclear and cellular expansion, ii) to supply membrane constituents for envelopment of capsids by budding at nuclear membranes and Golgi membranes, and iii) to provide membranes for formation of transport vacuoles.

  8. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Science.gov (United States)

    Abdelmagid, Nada; Bereczky-Veress, Biborka; Atanur, Santosh; Musilová, Alena; Zídek, Václav; Saba, Laura; Warnecke, Andreas; Khademi, Mohsen; Studahl, Marie; Aurelius, Elisabeth; Hjalmarsson, Anders; Garcia-Diaz, Ana; Denis, Cécile V; Bergström, Tomas; Sköldenberg, Birgit; Kockum, Ingrid; Aitman, Timothy; Hübner, Norbert; Olsson, Tomas; Pravenec, Michal; Diez, Margarita

    2016-01-01

    Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  9. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats with the asymptomatic infection of BN (Brown Norway. Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains, displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus named Hse6 towards the end of chromosome 4 (160.89-174Mb containing the Vwf (von Willebrand factor gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism. Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008 after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  10. Parvovirus and herpes simplex association with unexplained anemia in pregnancy: a prospective study.

    Science.gov (United States)

    Zaki, M El Sayed

    2008-10-01

    Anemia in pregnancy is a health problem in developing countries. Unexplained anemia constitutes about one-third of anemia. The purpose of the present study is to evaluate the association of parvovirus B19 and herpes simplex virus in pregnant females with unexplained anemia. The study included 100 pregnant patients with anaemia. Nutritional and hemolytic anemia were excluded. In addition, 24 healthy pregnant control were included. Virological markers for parvovirus B19 and herpes simplex were evaluated by PCR and specific IgM. Eighty-four patients had parvovirus infection as determined by positive PCR or/and positive IgM. While 40 patients had positive herpes simplex infection by positive PCR or/and IgM. Patients with parvovirus and herpes simplex infections either separately or had combined infections had significantly lower level of hemoglobin compared to patients negative for viruses infections (p=0.03, p=0.034, p<0.005 respectively). It can be concluded that both parvovirus B19 and herpes simplex are common among pregnant patients. Screening for parvovirus B19 and herpes simplex may help to reach for the diagnosis of unexplained anemia during first trimester of pregnancy and allow appropriate treatment to be offered.

  11. Asymptomatic Herpes Simplex Virus Shedding in STI Patients

    Institute of Scientific and Technical Information of China (English)

    叶兴东; 颜景兰; 朱慧兰; 张莉; 佟菊贞

    2002-01-01

    Objective: This study examined Herpes Simplex Virus(HSV) subclinical shedding in the genital tract of patients withgenital herpes (GH) or non-gonoccal urethritis (NGU). Method: Swabs were collected after exposure to rash andgenital tract during GH relapse or remission on a weekly basisfor four to six weeks. NGU patients with negative chlamydiaand mycoplasma tests were also swabbed for a similarduration. All swabs underwent HSV DNA detection withquantitative PCR. Result: There was a significant difference in the rate ofasymptomatic HSV shedding in urinary tracts comparing GHand the control group and comparing NGU and the controlgroup (P<0.05). The rate of HSV shedding was 22%, 9.8%and 3.3% for GH, NGU and control groups respectively. Therate of HSV shedding was 21.7% (20/92) for patients withactive GH and 23% for those in remission. The HSV positiverate was significantly higher in the group with patients whohad more than six relapses within one year compared to thegroup of patients with less than six GH relapses. Conclusion: There is HSV subclinical shedding in theirgenital tract during active GH and remission. SubclinicalHSV shedding is more common in patients with more than sixGH relapses per year compared to GH patients with fewerrelapses. Approximately 9.9% of NGU patients with negativechlamydia, mycoplasma testing was found to have subclinicalHSV infection.

  12. Temporal and Pontine Involvement in a Case of Herpes Simplex Encephalitis, Presenting as Kluver Bucy Syndrome - A Case Report

    Directory of Open Access Journals (Sweden)

    Suresh Thirunavukarasu

    2011-01-01

    Full Text Available Bilateral temporal and frontal lobe involvement is a common characteristic of herpes simplex encephalitis (HSE. Clinical sequelae of herpes simplex encephalitis may manifest sometimes as Kluver Bucy syndrome (KBS. In herpes simplex encephalitis, apart from frontal lobe, extra temporal involvement is rare and uncommon. We report a case of HSE manifesting clinically as KBS with a rare radiological finding of temporal and extratemporal involvement of pons.

  13. Serologic Screening for Herpes Simplex Virus among University Students: A Pilot Study

    Science.gov (United States)

    Mark, Hayley; Nanda, Joy P.; Joffe, Alain; Roberts, Jessica; Rompalo, Anne; Melendez, Johan; Zenilman, Jonathan

    2008-01-01

    Objective: The authors examined the feasibility of conducting serologic testing for the herpes simplex virus 2 (HSV-2) among university students and assessed the psychosocial impact of an HSV-2 diagnosis. Methods: The authors recruited a convenience sample of 100 students (aged 18-39 years) without a history of genital herpes from 1 university…

  14. Serologic Screening for Herpes Simplex Virus among University Students: A Pilot Study

    Science.gov (United States)

    Mark, Hayley; Nanda, Joy P.; Joffe, Alain; Roberts, Jessica; Rompalo, Anne; Melendez, Johan; Zenilman, Jonathan

    2008-01-01

    Objective: The authors examined the feasibility of conducting serologic testing for the herpes simplex virus 2 (HSV-2) among university students and assessed the psychosocial impact of an HSV-2 diagnosis. Methods: The authors recruited a convenience sample of 100 students (aged 18-39 years) without a history of genital herpes from 1 university…

  15. Seroprevalences of herpes simplex virus type 1 and type 2 among pregnant women in the Netherlands.

    NARCIS (Netherlands)

    Gaytant, M.A.; Steegers, E.A.P.; Laere, M. van; Semmekrot, B.A.; Groen, J.; Weel, J.F.; Meijden, W.I. van der; Boer, K.; Galama, J.M.D.

    2002-01-01

    BACKGROUND: In the Netherlands 73% of cases of neonatal herpes are caused by herpes simplex virus type 1 (HSV-1), whereas in the United States a majority are caused by HSV type 2 (HSV-2).GOAL To understand this difference we undertook a seroepidemiological study on the prevalence of HSV-1 and HSV-2

  16. Impact of Herpes simplex virus load and red blood cells in cerebrospinal fluid upon herpes simplex meningo-encephalitis outcome

    Directory of Open Access Journals (Sweden)

    Poissy Julien

    2012-12-01

    Full Text Available Abstract Background Herpes simplex encephalitis (HSE often leads to severe disability or death. Factors usually associated with outcome include Simplified Acute Physiology Score, age and delay of initiation of acyclovir treatment. Our aim was to determine the impact of Herpes simplex virus (HSV load in cerebrospinal fluid (CSF upon HSE outcome. Methods We retrospectively determined HSV load in the CSF of 43 patients with confirmed HSE, hospitalized in northern France from 1998 to 2005, using CSF samples collected the day of hospital admission and stored at −20°C. We analyzed the association between HSV load and mortality/morbidity by the Glasgow Outcome Scale. Fisher’s exact test and Wilcoxon’s test were used for statistical analysis. Results The M/F sex ratio was 1.7 and median patient age was 61 years. Median HSV load in CSF was 2.0 log copies/μL (IQR 25-75=1.2-2.6. The mortality rate was 32.6% six months after HSE diagnosis. Higher age was associated with mortality (p=0.03. Longer delay in acyclovir initiation tended to be associated with higher mortality but did not reach statistical significance (p=0.08. Severe disability and death due to HSV were associated with a higher Knaus score (p=0.004, later acyclovir initiation (p=0.006, older age (p=0.04 and presence of red blood cells in CSF (p=0.05. HSV load in CSF was neither associated with mortality (p=1.00 nor with morbidity (p=0.90. Conclusion In this study, HSV load in CSF was not found to be associated with poor outcome in patients with HSE. These data do not support measurement of HSV load at admission in patients with HSE.

  17. Peptide sequences of glycoprotein G-2 discriminate between herpes simplex virus type 2 (HSV-2) and HSV-1 antibodies.

    OpenAIRE

    Levi, M.; Rudén, U; Wahren, B.

    1996-01-01

    The complete herpes simplex virus type 2 envelope glycoprotein G was represented by overlapping synthetic peptides. Herpes simplex virus type 2-specific human seroreactivities were mainly seen against three peptides, peptides G2-64, G2-69, and G2-70, located in the C-terminal part of glycoprotein G. This is, interestingly, a region which has strong homology between herpes simplex virus types 1 and 2. G2-69 was the most herpes simplex virus type 2-specific peptide, reacting with 93% (13 of 14)...

  18. Necrotizing Keratitis Caused by Acyclovir-Resistant Herpes Simplex Virus

    Directory of Open Access Journals (Sweden)

    Koji Toriyama

    2014-10-01

    Full Text Available Background: We report a case of necrotizing keratitis caused by acyclovir (ACV-resistant herpes simplex virus (HSV with a clinical appearance similar to a previous fungal keratitis infection. Methods: Observational case report. Results: Penetrating keratoplasty was performed in the left eye with a history of herpetic keratitis that resolved with periodic treatment with ACV ointment and a topical steroid. The left eye was painful and red with an abscess and corneal erosion in the peripheral donor cornea. Examination of the scraped corneal epithelium by light microscopy and culturing identified Candida albicans; polymerase chain reaction (PCR was negative for human herpes viruses. After antifungal treatment, the ocular pain gradually decreased and the lesions slowly improved but recurred with a similar clinical appearance. A second light microscopy examination and cultures were negative for pathogens including C. albicans. PCR was positive for HSV-1 DNA; treatment with 3% topical ACV ointment was unsuccessful. A third examination showed only HSV-1 DNA. Despite antiviral ACV ointment, no clinical improvement occurred based on the HSV DNA copy numbers, which were the same before and after treatment, indicating a possible ACV-resistant strain. When topical trifluorothymidine was substituted for ACV, clinical improvement occurred and the HSV DNA copy numbers decreased. Conclusion: Necrotizing keratitis induced by ACV-resistant HSV occurred independently after fungal keratitis, with a similar clinical appearance in this case, making diagnosis and treatment difficult. Monitoring the HSV DNA load by real-time PCR could be useful for refractory cases even with atypical clinical appearances.

  19. Herpes simplex virus type 2: Seroprevalence in antenatal women

    Directory of Open Access Journals (Sweden)

    Rathore Shagufta

    2010-01-01

    Full Text Available Aims: To determine the seroprevalence of herpes simplex type 2 (HSV-2 infection in pregnant females, assess the frequency of unrecognized infection and identify the demographic profile and risk factors associated with the seroprevalence. Materials and Methods: Two hundred randomly selected, asymptomatic pregnant females attending the Obstetrics and Gynecology Outpatient Department for a routine antenatal check-up constituted the study group. Serum specimens were screened for HSV-2 infection by detecting IgG class antibodies against HSV-2-specific glycoprotein G-2 using an enzyme-linked immunosorbent assay kit. Results: A seroprevalence of 7.5% was found in our study. Seropositivity was maximum in the age group ≥30 years (22.20%, followed by 26-30 years (9.7%, 21-25 years (2.20% and ≤20 years (0%. HSV-2 seropositivity was found to be significantly associated with increasing age, parity, number of sexual partners, duration of sexual activity and history of abortions (P < 0.05. No statistically significant correlation was observed between seropositivity and other demographic variables such as place of residence, education, annual family income and occupation (P > 0.05. No statistically significant association of seropositivity with present or past history suggestive of other sexually transmitted infections was found. None of our cases tested positive for human immunodeficiency syndrome (HIV. Conclusion: A relatively low prevalence of HSV-2 seropositivity was found in our study, with a high frequency of unrecognized and asymptomatic infections. Our findings suggest that type-specific serotesting could be an efficient strategy to diagnose clinically asymptomatic HSV-2 infections and, therefore, to reduce the risk of HSV-2 and HIV sexual transmission by prophylactic counseling against unprotected intercourse. It may also be a useful adjunct in detecting cases who present with symptoms not directly suggestive of genital herpes.

  20. Tumores perianais provocados pelo herpes simples Perianal tumors provoked by herpes simplex

    Directory of Open Access Journals (Sweden)

    Sidney Roberto Nadal

    2007-03-01

    Full Text Available O Herpes simplex (HSV é um DNA vírus que provoca afecções perianais, sendo considerada a causa mais comum das úlceras na região. Apesar da forma ulcerativa ser a mais conhecida, a literatura relata o aparecimento de lesões tumorais, nodulares ou hipertróficas relacionadas ao vírus. O exame proctológico mostra tumores dolorosos, achatados, com superfície recoberta por ulceração rasa e com bordas bem delimitadas, elevadas e lobuladas, localizados na margem anal e/ou no sulco interglúteo, algumas vezes imitando condilomas virais ou carcinoma. A anamnese revela instalação insidiosa com crescimento lento e progressivo, além da história de tratamentos anteriores para úlceras herpéticas. O diagnóstico diferencial com carcinoma impõe a realização de biópsia para confirmação histológica. Esse exame revela hiperplasia epitelial moderada e denso processo inflamatório com linfócitos e plasmócitos. Células gigantes e multinucleadas são observadas na epiderme. Os testes imunohistoquímicos sugerem o HSV. A opção terapêutica inicial deve ser o tratamento medicamentoso. Importante definir o diagnóstico etiológico para aliviar o desconforto e evitar operação radical desnecessária, e introduzir medicação anti-retroviral nos portadores do HIV para melhora da imunidade.Herpes simplex is a DNA virus which provokes perianal lesions, and it is the most frequent etiology of anal ulcer. Despite the ulcerative herpes being known worldwide, literature relates a tumoral, or nodular, or hypertrophic form related to this virus. Proctological examination showed nodules with a verrucous appearance and an ulcerated surface at the anal margin, sometimes mimicking viral condylomas or carcinomas. Anamnesis reveals insidious installation, slow growth and prior treatments for herpetic ulcers. The differential diagnoses with cancer allow us to perform biopsies for histological confirmation. This exam reveals mild epithelial hyperplasia and

  1. Cytomegalovirus and herpes simplex infections in mothers and newborns in a Havana maternity hospital.

    Science.gov (United States)

    Festary, Aimée; Kourí, Vivian; Correa, Consuelo B; Verdasquera, Denis; Roig, Tania; Couret, Martha P

    2015-01-01

    Cytomegalovirus and herpes simplex virus are associated with congenital or perinatal infection, causing potential damage to the newborn. Determine the prevalence of active or latent infection by cytomegalovirus and herpes simplex virus in a population of mothers, congenital infection by these agents in their infants, and association between prevalence of virus infection in mothers and in their newborns. A cross-sectional study was conducted from June to September 2012 in a population of 95 pregnant women admitted to the Dr Ramón González Coro University Maternity Hospital during the third trimester of pregnancy, and their infants (98). Patients were tested for antibodies specific to these viruses; vaginal swabs and urine from the women and serum and urine from the newborns were tested for viral genome. The Fisher exact test with 95% confidence interval was used for comparisons. Of the women studied, 89.5% tested positive for cytomegalovirus and 83.2% for herpes simplex. Active infection from cytomegalovirus was detected in 16.7%, and from herpes simplex in 3.2%. Congenital cytomegalovirus infection was detected in 4.1% of newborns; no herpes simplex virus infection was found in this group. Two newborns of women with active cytomegalovirus infection were congenitally infected. Serology demonstrated that most of the women were immune to both viruses. Active cytomegalovirus infections are common in this population, and newborns of women with active cytomegalovirus infection during pregnancy are at increased risk of congenital infection.

  2. Herpes simplex virus type 1-derived recombinant and amplicon vectors.

    Science.gov (United States)

    Fraefel, Cornel; Marconi, Peggy; Epstein, Alberto L

    2011-01-01

    Herpes simplex virus type 1 (HSV-1) is a human pathogen whose lifestyle is based on a long-term dual interaction with the infected host, being able to establish both lytic and latent infections. The virus genome is a 153 kbp double-stranded DNA molecule encoding more than 80 genes. The interest of HSV-1 as gene transfer vector stems from its ability to infect many different cell types, both quiescent and proliferating cells, the very high packaging capacity of the virus capsid, the outstanding neurotropic adaptations that this virus has evolved, and the fact that it never integrates into the cellular chromosomes, thus avoiding the risk of insertional mutagenesis. Two types of vectors can be derived from HSV-1, recombinant vectors and amplicon vectors, and different methodologies have been developed to prepare large stocks of each type of vector. This chapter summarizes (1) the two approaches most commonly used to prepare recombinant vectors through homologous recombination, either in eukaryotic cells or in bacteria, and (2) the two methodologies currently used to generate helper-free amplicon vectors, either using a bacterial artificial chromosome (BAC)-based approach or a Cre/loxP site-specific recombination strategy.

  3. Herpes Simplex Virus Latency: The DNA Repair-Centered Pathway

    Directory of Open Access Journals (Sweden)

    Jay C. Brown

    2017-01-01

    Full Text Available Like all herpesviruses, herpes simplex virus 1 (HSV1 is able to produce lytic or latent infections depending on the host cell type. Lytic infections occur in a broad range of cells while latency is highly specific for neurons. Although latency suggests itself as an attractive target for novel anti-HSV1 therapies, progress in their development has been slowed due in part to a lack of agreement about the basic biochemical mechanisms involved. Among the possibilities being considered is a pathway in which DNA repair mechanisms play a central role. Repair is suggested to be involved in both HSV1 entry into latency and reactivation from it. Here I describe the basic features of the DNA repair-centered pathway and discuss some of the experimental evidence supporting it. The pathway is particularly attractive because it is able to account for important features of the latent response, including the specificity for neurons, the specificity for neurons of the peripheral compared to the central nervous system, the high rate of genetic recombination in HSV1-infected cells, and the genetic identity of infecting and reactivated virus.

  4. Stabilising the Herpes Simplex Virus capsid by DNA packaging

    Science.gov (United States)

    Wuite, Gijs; Radtke, Kerstin; Sodeik, Beate; Roos, Wouter

    2009-03-01

    Three different types of Herpes Simplex Virus type 1 (HSV-1) nuclear capsids can be distinguished, A, B and C capsids. These capsids types are, respectively, empty, contain scaffold proteins, or hold DNA. We investigate the physical properties of these three capsids by combining biochemical and nanoindentation techniques. Atomic Force Microscopy (AFM) experiments show that A and C capsids are mechanically indistinguishable whereas B capsids already break at much lower forces. By extracting the pentamers with 2.0 M GuHCl or 6.0 M Urea we demonstrate an increased flexibility of all three capsid types. Remarkably, the breaking force of the B capsids without pentamers does not change, while the modified A and C capsids show a large drop in their breaking force to approximately the value of the B capsids. This result indicates that upon DNA packaging a structural change at or near the pentamers occurs which mechanically reinforces the capsids structure. The reported binding of proteins UL17/UL25 to the pentamers of the A and C capsids seems the most likely candidate for such capsids strengthening. Finally, the data supports the view that initiation of DNA packaging triggers the maturation of HSV-1 capsids.

  5. The herpes simplex virus virion host shutoff function.

    Science.gov (United States)

    Kwong, A D; Frenkel, N

    1989-11-01

    The virion host shutoff (vhs) function of herpes simplex virus (HSV) limits the expression of genes in the infected cells by destabilizing both host and viral mRNAs. vhs function mutants have been isolated which are defective in their ability to degrade host mRNA. Furthermore, the half-life of viral mRNAs is significantly longer in cells infected with the vhs-1 mutant virus than in cells infected with the wild-type (wt) virus. Recent data have shown that the vhs-1 mutation resides within the open reading frame UL41. We have analyzed the shutoff of host protein synthesis in cells infected with a mixture of the wt HSV-1 (KOS) and the vhs-1 mutant virus. The results of these experiments revealed that (i) the wt virus shutoff activity requires a threshold level of input virions per cell and (ii) the mutant vhs-1 virus protein can irreversibly block the wt virus shutoff activity. These results are consistent with a stoichiometric model in which the wt vhs protein interacts with a cellular factor which controls the half-life of cell mRNA. This wt virus interaction results in the destabilization of both host and viral mRNAs. In contrast, the mutant vhs function interacts with the cellular factor irreversibly, resulting in the increased half-life of both host and viral mRNAs.

  6. Detection of Herpes Simplex Virus DNA in Pseudoexfoliation Syndrome

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    Masoomeh Eghtedari

    2009-06-01

    Full Text Available Background: Pseudoexfoliation syndrome is one of the mostcommon identifiable causes of open angle glaucoma. It hasunknown etiology and pathogenesis. Infection, possibly viral,is one of the proposed pathogenic mechanisms in this condition.In the present study the presence of herpes simplex virus(HSV in specimens of anterior lens capsule of patients withpseudoexfoliation syndrome has been assessed.Methods: The presence of HSV- DNA was searched by usingpolymerase chain reaction method in specimens of anteriorlens capsule (5 mm diameter of 50 patients with pseudoexfoliationsyndrome (study group and 50 age-matchedpatients without the disease (control group who underwentcataract or combined cataract and glaucoma surgery duringa one-year (2006-2007 period in Khalili Hospital, Shiraz,Iran. The results were compared statistically with Chisquaretest and independent samples t test using SPSS software(version 11.5.Results: HSV type I DNA was detected in 18% of the patientsin the study group compared with 2% in the control group (Chisquare test, P = 0.008. The difference between the ranges ofintraocular pressure in the two groups was not statistically significant.Conclusion: The presence of HSV type I DNA suggests thepossible relationship between the virus and pseudoexfoliationsyndrome. It may be a treatable etiology in this multi-factorialdisorder and may help to future management of patients; especiallyto prevent some of the complications in this syndrome.

  7. Higher Throughput Quantification of Neutralizing Antibody to Herpes Simplex Viruses.

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    Tamara P Blevins

    Full Text Available We report a rapid, higher throughput method for measuring neutralizing antibody to herpes simplex virus (HSV in human sera. Clinical isolates and sera from the Herpevac Trial for Women were used in a colorimetric assay in which infection of tissue culture (lack of neutralization was indicated by substrate metabolism by beta-galactosidase induced in the ELVIS cell line. The neutralization assay was optimized by addition of guinea pig complement, which particularly enhanced neutralizing antibody titers to HSV-2. Higher neutralizing antibody titers were also achieved using virus particles isolated from the supernatant of infected cells rather than lysate of infected cells as the source of virus. The effect of assay incubation time and incubation time with substrate were also optimized. We found that incubating with substrate until a standard optical density of 1.0 was reached permitted a better comparison among virus isolates, and achieved reliable measurement of neutralizing antibody activity. Interestingly, in contrast to results in the absence of complement, addition of complement allowed sera from HSV-2 gD-vaccinated subjects to neutralize HSV-1 and HSV-2 clinical and laboratory isolates with equal potency.

  8. Whole Blood Polymerase Chain Reaction in a Neonate with Disseminated Herpes Simplex Virus Infection and Liver Failure

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    Jennifer A. Scoble

    2013-10-01

    Full Text Available A late preterm neonate born by cesarean section with intact membranes presented at 9 days of life with shock and liver failure. Surface cultures were negative but whole blood polymerase chain reaction was positive for herpes simplex virus type 2, underscoring the value of this test in early diagnosis of perinatally acquired disseminated herpes simplex virus infection without skin lesions.

  9. Herpes zoster is associated with herpes simplex and other infections in under 60 year-olds.

    Science.gov (United States)

    Ogunjimi, Benson; Buntinx, Frank; Bartholomeeusen, Stephaan; Terpstra, Ita; De Haes, Inke; Willem, Lander; Elli, Steven; Bilcke, Joke; Van Damme, Pierre; Coenen, Samuel; Beutels, Philippe

    2015-02-01

    We assessed the association between herpes zoster (HZ) and herpes simplex (HS) occurrence whilst controlling for risk factors of HZ. Using a Belgian general practitioner network, a retrospective cohort study with 3736 HZ patients and 14,076 age-gender-practice matched controls was performed, covering over 1.5 million patient-years. Multiple logistic regression was used with HZ as outcome and several diagnoses (malignancy, depression, diabetes mellitus, auto-immune diseases, asthma, multiple sclerosis, HIV, fractures), medications (systemic corticosteroids, biologicals, vaccination), HS and other infections as variables. HS was significantly associated with HZ for all analysed time intervals (up to five years) post HZ (OR of 3.51 [2.09 5.88] 95%CI one year post HZ) and to a lesser extent for time ranges pre HZ. Registration of other infections was significantly associated with HZ in all time intervals pre and post HZ (OR up to 1.37). Malignancy up to five years pre HZ, depression up to one year pre or post HZ, fractures up to two years pre HZ, asthma, auto-immune diseases, and immunosuppressive medication one year pre or post HZ were also associated with HZ. HZ and HS occurrences are significantly associated and potentially share a common susceptibility beyond the known risk factors. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  10. Bilateral herpes simplex keratitis in a patient with chronic graft-versus-host disease

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    Takahiko Hayashi

    2008-06-01

    Full Text Available Takahiko Hayashi1, Misaki Ishioka2, Norihiko Ito1, Yoko Kato1, Hisashi Nakagawa3, Hiroshi Hatano4, Nobuhisa Mizuki11Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan; 2Ryogoku Eye Clinic, Tokyo, Japan; 3Tokushima Eye Clinic, Higashimurayama-shi, Tokyo, Japan; 4Lumine Hatano Eye Clinic, Fujisawa, Fujisawa-shi, Kanagawa, JapanPurpose: To describe a case of bilateral herpes simplex keratitis accompanying chronic graft-versus-host disease (GVHD.Design: Observational case report.Case report: An 11-year-old boy with myelocytic leukemia underwent allogeneic bone marrow transplantation. He developed symptoms of the skin, eyes, and mouth, and lip biopsy indicated chronic GVHD. Persistent keratitis with corneal filaments and neovascularization was noted in both eyes. Sodium hyaluronate, autoserum, and 0.1% fluorometholone eyedrops were instilled for approximately 2 years to treat this keratitis, and there were no other ocular changes. Bilateral herpes simplex keratitis developed with geographic ulcers after topical betamethasone therapy, but responded to acyclovir ointment.Conclusions: Herpes keratitis should be considered in the differential diagnosis of bilateral keratitis in patients with reduced immunocompetence. During the course of chronic GVHD, corneal herpes may occur, so ocular treatment with topical corticosteroids should be managed by an ophthalmologist to monitor sight-threatening conditions such as corneal herpes.Keywords: chronic graft-versus-host disease, bone marrow transplant, corneal herpes, bilateral herpes simplex keratitis, dry eyes

  11. Anterior opercular syndrome as a first presentation of herpes simplex encephalitis.

    Science.gov (United States)

    De Kleermaeker, Floriaan G C M; Bouwmans, Angela E P; Nicolai, Joost; Klinkenberg, Sylvia

    2014-04-01

    We report a 5-year-old girl who presented with fever, drooling, dysphagia, and anarthria. Moreover, voluntary facial movements were disturbed, but the emotional facial movements were completely normal. This clinical phenomenon is known as the anterior opercular syndrome. There was a positive polymerase chain reaction for herpes simplex in the cerebrospinal fluid. The diagnosis herpes simplex encephalitis was supported by both magnetic resonance images (MRI) as by electroencephalogram (EEG). Herpes simplex encephalitis is a rare, but severe, cause of the anterior opercular syndrome that demands treatment as soon as possible in order to prevent high morbidity or mortality. The phenomenon of autonomic-voluntary dissociation, associated with other clinical and radiologic findings related to an underlying neurologic disorder, alerts clinicians to the anterior opercular syndrome as a critical diagnostic observation with time-dependent therapeutic consequences.

  12. Association between recent herpes zoster but not herpes simplex infection and subsequent risk of malignancy in women: a retrospective cohort study.

    Science.gov (United States)

    Buntinx, F; Bartholomeeusen, S; Belmans, A; Mathei, C; Opdenakker, G; Sweldens, K; Truyers, C; Van Ranst, M

    2014-05-01

    The association between herpes zoster and subsequent cancer risk is still unclear. Consequently, doubts remain regarding the need for investigation of herpes patients for co-existing or subsequent malignancy. This is a retrospective cohort study comparing cancer risk in patients after herpes zoster and age-/sex-matched non-herpes zoster patients, in a primary care-based continuous morbidity database. We tested for interaction by gender, age, diabetes, HRT use or antiviral therapy. Analyses were repeated for patients with and without herpes simplex. The hazard ratio (HR) comparing cancer risk in herpes zoster vs. control patients was significant in all women, women aged > 65 years and subgroups of breast and colorectal cancer (HRs 1·60, 1·82, 2·14, 2·19, respectively). For men, a significant association was found for haematological cancers (HR 2·92). No associations were found with herpes simplex. No interaction was identified with antiviral therapy, diabetes or HRT treatment. We concluded that there was a moderate significant association between herpes zoster and subsequent cancer risk in women aged > 65 years, without any influence of antiviral therapy. No association was found with herpes simplex. There is insufficient reason for extensively testing older patients with herpes zoster or herpes simplex for the presence of occult cancer.

  13. A Case of Fetal Herpes Simplex Encephalitis Diagnosed Prenatally by Ultrasonography in the Third Trimester

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mi Bum; Kim, Yu Ri; Hwang, Han Sung; Park, Yong Won; Kim, Young Han [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-12-15

    Almost all reported incidences of herpes simplex virus (HSV) infection in newborns result as a complication of rupture of the amniotic membranes or the delivery of the baby, but infection via the placenta and amniotic membranes is rare. Ventriculomegaly was detected at 36 weeks of gestation by prenatal ultrasonography, and an emergency cesarean section was then performed at 36 weeks of gestation. We report a case of herpes simplex encephalitis detected at 36 weeks of gestation by prenatal ultrasonography, which was confirmed by a postnatal serologic test and CSF test with a brief review of literature

  14. Herpes simplex encephalitis: MRI findings in two cases confirmed by polymerase chain reaction assay

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J.W.; Kim, I.O.; Kim, W.S.; Yeon, K.M. [Dept. of Radiology and the Institute of Radiation Medicine, Seoul National University Hospital, Seoul (Korea); Lee, H.-J.; Hwang, Y.S. [Dept. of Paediatrics, Seoul National University College of Medicine, Seoul (Korea)

    2001-09-01

    Herpes simplex virus (HSV) type I causes a fulminant necrotising meningoencephalitis distinguished from other encephalitides by its focal and often haemorrhagic nature. Specific antiviral therapy with acyclovir can significantly improve the prognosis. We present MRI findings of two cases of herpes simplex encephalitis (HSE) confirmed by PCR analysis, focusing on the serial changes after acyclovir therapy: gyral swelling, high signal intensity on T2-weighted images in the subfrontal region, temporal lobe and insula in the initial stage, then regional extension with enhancement and haemorrhage despite appropriate acyclovir therapy, and finally encephalomalacia and brain atrophy. (orig.)

  15. Concurrent Reactivation of Herpes Simplex and Varicella Zoster Viruses Confirmed by the Loop-Mediated Isothermal Amplification Assay

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    Tsukane Kobayashi

    2014-01-01

    Full Text Available Concurrent reactivation of herpes simplex and varicella zoster viruses is rare. Here, we describe the case of an elderly patient with herpes labialis and herpes zoster manifesting as a right-side facial eruption with vesicles and crusting. The loop-mediated isothermal amplification (LAMP assay demonstrated the presence of both herpes simplex virus type 1 and varicella zoster virus in swab samples taken from the face, which was confirmed by real-time PCR, suggesting concurrent reactivation of both viruses. The use of the LAMP assay in the present case indicates its usefulness in the diagnosis of atypical herpes infections.

  16. A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

    OpenAIRE

    2015-01-01

    Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephaliti...

  17. Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

    OpenAIRE

    Vadlapudi, Aswani D.; Vadlapatla, Ramya K.; Mitra, Ashim K.

    2013-01-01

    Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly i...

  18. Piroxicam inhibits herpes simplex virus type 1 infection in vitro.

    Science.gov (United States)

    Astani, A; Albrecht, U; Schnitzler, P

    2015-05-01

    Piroxicam is a potent, nonsteroidal, anti-inflammatory agent (NSAID) which also exhibits antipyretic activity. The antiviral effect of piroxicam against herpes simplex virus type 1 (HSV-1) was examined in vitro on RC-37 monkey kidney cells using a plaque reduction assay. Piroxicam was dissolved in ethanol or dimethylsulfoxide (DMSO) and the 50% inhibitory concentration (IC50) was determined at 4 μg/ml and 75 μg/ml, respectively. The IC50 for the standard antiherpetic drug acyclovir was determined at 1.6 μM. At non-cytotoxic concentrations of these piroxicam solutions, plaque formation was significantly reduced by 62.4% for ethanolic piroxicam and 72.8% for piroxicam in DMSO. The mode of antiviral action of these drugs was assessed by time-on-addition assays. No antiviral effect was observed when cells were incubated with piroxicam prior to infection with HSV-1 or when HSV-1 infected cells were treated with dissolved piroxicam. Herpesvirus infection was, however, significantly inhibited when HSV-1 was incubated with piroxicam prior to the infection of cells. These results indicate that piroxicam affected the virus before adsorption, but not after penetration into the host cell, suggesting that piroxicam exerts a direct antiviral effect on HSV-1. Free herpesvirus was sensitive to piroxicam in a concentration-dependent manner and the inhibition of HSV-1 appears to occur before entering the cell but not after penetration of the virus into the cell. Considering the lipophilic nature of piroxicam, which enables it to penetrate the skin, it might be suitable for topical treatment of herpetic infections.

  19. Effect of combinations of antiviral drugs on herpes simplex encephalitis

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    Bryan M Gebhardt

    2009-12-01

    Full Text Available Bryan M Gebhardt1, Federico Focher2, Richard Eberle3, Andrzej Manikowski4, George E Wright41LSU Eye Center, Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA, USA; 2Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy; 3Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA; 4GLSynthesis Inc., Worcester, MA, USAAbstract: 2-Phenylamino-6-oxo-9-(4-hydroxybutylpurine (HBPG is a thymidine kinase inhibitor that prevents encephalitic death in mice caused by herpes simplex virus (HSV types 1 and 2, although its potency is somewhat less than that of acyclovir (ACV. The present study was undertaken to determine the effect of combinations of HBPG and either ACV, phosphonoformate (PFA, or cidofovir (CDF against HSV encephalitis. BALB/c mice were given ocular infections with HSV-1 or HSV-2, and treated twice daily intraperitoneally for five days with HBPG, alone or in combination with ACV, PFA, or CDF. Animals were observed daily for up to 30 days, and the day of death of each was recorded. All of the combinations showed additivity, and the combination of HBPG + ACV appeared to be synergistic, ie, protected more mice against HSV-1 encephalitis compared with each drug given alone. Delay of treatment with HBPG for up to two days was still effective in preventing HSV-2 encephalitis. The combination of the thymidine kinase inhibitor HBPG and the antiherpes drug ACV may have synergistic activity against HSV encephalitis. The development of a potent and safe combination therapy for the prevention and/or treatment of HSV infection of the central nervous system can improve the outcome of this infection in humans.Keywords: antivirals, herpetic encephalitis

  20. Can we differentiate between herpes simplex encephalitis and Japanese encephalitis?

    Science.gov (United States)

    Kalita, Jayantee; Misra, Usha Kant; Mani, Vinita Elizabeth; Bhoi, Sanjeev Kumar

    2016-07-15

    Herpes simplex encephalitis (HSE) occurs without regional and seasonal predilections. HSE is important to differentiate from arboviral encephalitis in endemic areas because of therapeutic potential of HSE. This study evaluates clinical features, MRI and laboratory findings which may help in differentiating HSE from Japanese encephalitis (JE). Confirmed patients with JE and HSE in last 10years were included. The presenting clinical symptoms including demographic information, seizure, behavioral abnormality, focal weakness and movement disorders were noted. Cranial MRI was done and location and nature of signal alteration were noted. Electroencephalography (EEG), cerebrospinal fluid (CSF), blood counts and serum chemistry were done. Outcome was measured by modified Rankin Scale (mRS). Death, functional outcome and neurological sequelae were noted at 3, 6 and 12months follow up, and compared between HSE and JE. Outcome was categorized as poor (mRS;>2) and good (mRS≤2). 97 patients with JE and 40 HSE were included. JE patients were younger than HSE and occurred in post monsoon period whereas HSE occurred throughout the year. Seizure (86% vs 40%) and behavioral abnormality (48% vs 10%) were commoner in HSE; whereas movement disorders (76% vs 0%) and focal reflex loss (42% vs 10%) were commoner in JE. CSF findings and laboratory parameters were similar in both the groups. Thalamic involvement in JE and temporal involvement in HSE were specific markers of respective encephalitis. Delta slowing on EEG was more frequent in JE than HSE. 20% JE and 30% HSE died in the hospital, and at 1year follow up JE patients showed better outcome compared to HSE (48% vs 24%). Memory loss (72% vs 22%) was the predominant sequelae in HSE. Seizure and behavioral abnormality are common features in HSE whereas focal reflex loss is commoner in JE. In a patient with acute encephalitis, thalamic lesion suggests JE and temporal lobe involvement HSE. Long term outcome in JE is better compared to

  1. Imaging findings of neonatal herpes simplex virus type 2 encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Vossough, Arastoo; Zimmerman, Robert A.; Bilaniuk, Larissa T.; Schwartz, Erin M. [University of Pennsylvania, Children' s Hospital of Philadelphia, Philadelphia, PA (United States)

    2008-04-15

    The CT, MR, and diffusion-weighted initial and follow-up imaging findings in neonatal herpes simplex virus type 2 (HSV-2) encephalitis were assessed. The clinical, laboratory and imaging findings in 12 patients (eight girls and four boys) with proven neonatal HSV-2 encephalitis with follow-up were retrospectively reviewed. Patterns of brain involvement and distribution of lesions were studied and the contribution of diffusion-weighted imaging to the imaging diagnosis of this disease was explored. A total of 24 CT and 22 MRI studies were performed with a mean follow-up time of 38 months. Neonatal HSV-2 encephalitis can be multifocal or limited to only the temporal lobes, brainstem, or cerebellum. The deep gray matter structures were involved in 57% of patients, and hemorrhage was seen in more than half of the patients. CT images were normal or showed mild abnormalities in the early stages of the disease. Conventional MR images may be normal in the early stages of the disease. Lesions were initially seen only by diffusion-weighted imaging in 20% of the patients and this modality showed a substantially more extensive disease distribution in an additional 50% of patients. In 40% of patients, watershed distribution ischemic changes were observed in addition to areas of presumed direct herpetic necrosis. Neonatal HSV-2 encephalitis has a variable imaging appearance. Diffusion-weighted MRI is an important adjunct in the imaging evaluation of this disease. Watershed distribution ischemia in areas remote from the primary herpetic lesions may be seen. (orig.)

  2. Estudio de sensibilidad antiviral de Virus Herpes simplex en pacientes trasplantados Antiviral sensitivity of Herpes simplex virus in immunocompromised patients

    Directory of Open Access Journals (Sweden)

    H. Illán

    2004-06-01

    Full Text Available La resistencia de virus Herpes simplex (VHS a Aciclovir (ACV ocurre en aproximadamente un 5% de los pacientes inmunocomprometidos. El tratamiento con análogos de nucleósidos, provoca la aparición de cepas VHS-ACV resistentes (ACVr. El mecanismo responsable de la resistencia a ACV son las mutaciones en los genes que codifican las enzimas timidina quinasa y/o ADN- polimerasa. En un estudio de aislamientos clinicos de pacientes inmunodeficientes, se encontró que el 96% de los VHS ACVr son debidos a una baja producción o ausencia de la enzima y un4% son cepas con alteración de la especificidad por el sustrato, casi no se obtuvieron cepas mutantes en la ADN-polimerasa (15. Los análogos de Pirofosfatos generan resistencia por mutación en el gen de la ADN-polimerasa. En este trabajo se presenta la metodología empleada para el estudio de los perfiles de sensibilidad a ACV y a Foscarnet (PFA en una población de inmunosuprimidos. Se estudiaron 46 aislamientos de VHS en fibroblastos humanos, provenientes de muestras de trasplantados con lesiones vesiculares. De los 46 aislamientos, 26 resultaron VHS-1 y 20 VHS-2, tipificados por Inmunofluorescencia (IF con anticuerpos monoclonales. Posteriormente se amplificaron y se les determinó su perfíl de sensibilidad en células Vero, utilizando 100 Dosis infectivas en cultivo de tejidos 50% (DICT50 de cada cepa viral y las drogas antivirales en diferentes concentraciones. La concentración inhibitoria 50%(CI50 se calculó a partir del porcentaje de inhibición del efecto citopático en función de la concentración de la droga. Ninguno de los aislamientos resultó resistente al PFA y solo dos de ellos, uno de VHS-1 y uno de VHS-2, fueron resistentesa ACV.The Herpes simplex Virus (HSV resistance to acyclovir (ACV occurs in a 5% of the inmunocompromised patients, approximately. The treatment with analogs of nucleosides, causes the appearance of resistent HSV-ACV stocks(ACVr which can be produced by

  3. Cutaneous neonatal herpes simplex virus infection type 2: a case report*

    Science.gov (United States)

    Bittencourt, Maraya de Jesus Semblano; Freitas, Lívia Karlla Marinho; Drago, Marion Guimarães; Carvalho, Alessandra Haber; do Nascimento, Bianca Angelina Macêdo

    2016-01-01

    Neonatal herpes is a serious condition. Newborns can be contaminated in utero via transplacental hematogenic transmission, upon delivery (the most frequent route), or during the postnatal period (indirect transmission). Optimal management requires prompt and accurate recognition, particularly in newborns, in order to prevent complications. Acyclovir is the treatment of choice, but its implementation is often delayed while awaiting test results, such as PCR and serology. Cytology for diagnostic purposes is rarely used in dermatology, despite the quick and reliable results. We report a case of neonatal herpes caused by type 2 herpes simplex virus diagnosed by cytology. PMID:27192523

  4. Molecular and serologic diagnostic approaches; the prevalence of herpes simplex in idiopathic men infertile

    Science.gov (United States)

    Amirjannati, Nasser; Yaghmaei, Farhad; Akhondi, Mohammad Mehdi; Nasiri, Mahboubeh; Heidari-Vala, Hamed; Sehhat, Zahra

    2014-01-01

    Background: Human pathogens that can cause infertility may also affect sperm count and quality. Viral infections can be considered as direct and/or indirect cause of male factor infertility. Objective: Our goal was to investigate the prevalence of herpes simplex virus in the semen of infertile men attending the Avicenna Infertility Clinic, and to compare it with the herpes virus serology results. Materials and Methods: This cross sectional study was conducted during 2009-2010. Infertile men participating without any clinical signs of infection with herpes simplex virus, and no obvious cause for their infertility were included. Semen and blood samples were used for Polymerase Chain Reaction (PCR) and serologic testing for these people. Two samples were collected: one ml semen sample to verify the existence of genital herpes simplex virus in infertile men, and blood samples of 217 individuals tested for antibodies to herpes simplex virus. Data were analyzed by SPSS 16. Results: According to the PCR results of semen samples the prevalence of herpes simplex in semen was 12% and serologic test showed 3.2% prevalence within blood. Nine to 10% of IgM negative were PCR positive and only 2-3% of IgM positive were PCR positive. Between herpes serologic studies with positive controls and negative controls by using both tests, there was a significant positive relationship (r=0.718 and p<0.001). The relationship between semen PCR test results and serological survey of herpes patients with a negative control in both Pearson and Spearman tests was positive and significant (r=0.229 and p=0.001). Correlation between the PCR results of semen samples with two positive control subjects and a positive IgM test was statistically confirmed (r=0.235 and p<0.001). Conclusion: We recommend that if there is suspicion to herpes simplex as a microorganism that theoretically could impact semen parameters and cause infertility it is prudent to use PCR technique on semen sample rather than ELISA

  5. Identification and Characterization of the UL37 Protein of Herpes Simplex Virus Type 1 and Demonstration that it Interacts with ICP8, the Major DNA Binding Protein of Herpes Simplex Virus

    Science.gov (United States)

    1992-10-20

    simplex. J.A.M.A. 117:999-1005 . Segal, A.L. t A.H. Katcher, V.J. Brightman, and M. F . Miller. 1974. Recurrent herpes labialis , recurrent aphthous...AII’I fORCE MEDICAL C(NTEIt Title of Dissertation : "Ideatification and Characterization of the UL37 Protein of Herpes Simplex Virus Type 1 and...Demonstration that It Interacts with reps. the Major DNA Binding Protein of Herpes Simplex Virus" Name of Candidate: Lisa Shelton Doctor of

  6. Concomitant herpes simplex virus colitis and hepatitis in a man with ulcerative colitis: Case report and review of the literature.

    Science.gov (United States)

    Phadke, Varun K; Friedman-Moraco, Rachel J; Quigley, Brian C; Farris, Alton B; Norvell, J P

    2016-10-01

    Herpesvirus infections often complicate the clinical course of patients with inflammatory bowel disease; however, invasive disease due to herpes simplex virus is distinctly uncommon. We present a case of herpes simplex virus colitis and hepatitis, review all the previously published cases of herpes simplex virus colitis, and discuss common clinical features and outcomes. We also discuss the epidemiology, clinical manifestations, diagnosis, and management of herpes simplex virus infections, focusing specifically on patients with inflammatory bowel disease. A 43-year-old man with ulcerative colitis, previously controlled with an oral 5-aminosalicylic agent, developed symptoms of a colitis flare that did not respond to treatment with systemic corticosteroid therapy. One week later he developed orolabial ulcers and progressive hepatic dysfunction, with markedly elevated transaminases and coagulopathy. He underwent emergent total colectomy when imaging suggested bowel micro-perforation. Pathology from both the colon and liver was consistent with herpes simplex virus infection, and a viral culture of his orolabial lesions and a serum polymerase chain reaction assay also identified herpes simplex virus. He was treated with systemic antiviral therapy and made a complete recovery. Disseminated herpes simplex virus infection with concomitant involvement of the colon and liver has been reported only 3 times in the published literature, and to our knowledge this is the first such case in a patient with inflammatory bowel disease. The risk of invasive herpes simplex virus infections increases with some, but not all immunomodulatory therapies. Optimal management of herpes simplex virus in patients with inflammatory bowel disease includes targeted prophylactic therapy for patients with evidence of latent infection, and timely initiation of antiviral therapy for those patients suspected to have invasive disease.

  7. Herpes Simplex Virus (HSV-1 Encephalitis Mimicking Glioblastoma: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Burke A. Cunha

    2014-12-01

    Full Text Available Glioblastoma multiforme (GBM often presents as a brain mass with encephalitis. In a patient with GBM, subsequent presentation with new onset encephalitis may be due to another GBM or Herpes simplex virus 1 (HSV-1 encephalitis. We present a case of HSV-1 encephalitis mimicking GBM in a patient with previous GBM.

  8. Molecular requirement for sterols in herpes simplex virus entry and infectivity

    Science.gov (United States)

    Herpes simplex virus 1 (HSV-1) required cholesterol for virion-induced membrane fusion. HSV successfully entered DHCR24-/-cells, which lack a desmosterol-to-cholesterol conversion enzyme, indicating entry can occur independently of cholesterol. Depletion of desmosterol from these cells resulted in d...

  9. Oncolytic Herpes Simplex Viral Therapy: A Stride toward Selective Targeting of Cancer Cells.

    Science.gov (United States)

    Sanchala, Dhaval S; Bhatt, Lokesh K; Prabhavalkar, Kedar S

    2017-01-01

    Oncolytic viral therapy, which makes use of replication-competent lytic viruses, has emerged as a promising modality to treat malignancies. It has shown meaningful outcomes in both solid tumor and hematologic malignancies. Advancements during the last decade, mainly genetic engineering of oncolytic viruses have resulted in improved specificity and efficacy of oncolytic viruses in cancer therapeutics. Oncolytic viral therapy for treating cancer with herpes simplex virus-1 has been of particular interest owing to its range of benefits like: (a) large genome and power to infiltrate in the tumor, (b) easy access to manipulation with the flexibility to insert multiple transgenes, (c) infecting majority of the malignant cell types with quick replication in the infected cells and (d) as Anti-HSV agent to terminate HSV replication. This review provides an exhaustive list of oncolytic herpes simplex virus-1 along with their genetic alterations. It also encompasses the major developments in oncolytic herpes simplex-1 viral therapy and outlines the limitations and drawbacks of oncolytic herpes simplex viral therapy.

  10. Herpes Simplex Virus Infection in a University Health Population: Clinical Manifestations, Epidemiology, and Implications

    Science.gov (United States)

    Horowitz, Robert; Aierstuck, Sara; Williams, Elizabeth A.; Melby, Bernette

    2010-01-01

    Objective: The authors described clinical presentations of oral and genital herpes simplex virus (HSV) infections in a university health population and implications of these findings. Participants and Methods: Using a standardized data collection tool, 215 records of patients with symptomatic culture-positive HSV infections were reviewed. Results:…

  11. Herpes Simplex Virus Infection in a University Health Population: Clinical Manifestations, Epidemiology, and Implications

    Science.gov (United States)

    Horowitz, Robert; Aierstuck, Sara; Williams, Elizabeth A.; Melby, Bernette

    2010-01-01

    Objective: The authors described clinical presentations of oral and genital herpes simplex virus (HSV) infections in a university health population and implications of these findings. Participants and Methods: Using a standardized data collection tool, 215 records of patients with symptomatic culture-positive HSV infections were reviewed. Results:…

  12. 75 FR 59611 - Microbiology Devices; Reclassification of Herpes Simplex Virus Types 1 and 2 Serological Assays...

    Science.gov (United States)

    2010-09-28

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 Microbiology Devices; Reclassification of Herpes Simplex Virus Types 1 and 2 Serological Assays; Confirmation of Effective Date AGENCY: Food and...

  13. N-Methyl-D-Aspartate Receptor Antibodies in Herpes Simplex Encephalitis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-02-01

    Full Text Available Researchers at Charite University Medicine Berlin, and other centers in Germany, Spain and the US performed a retrospective analysis of 44 patients with polymerase chain reaction-proven herpes simplex encephalitis (HSE for the presence of onconeuronal and synaptic receptor antibodies.

  14. Monitoring of herpes simplex virus thymidine kinase enzyme activity using positron emission tomography

    NARCIS (Netherlands)

    Hospers, GAP; Calogero, Anna; van Waarde, A; Doze, P; Vaalburg, W; Mulder, NH; de Vries, EFJ

    2000-01-01

    9-[(1-[F-18]Fluoro-3-hydroxy-2-propoxy)methyl]guanine ([F-18]FHPG) wasevaluated as a tracer for noninvasive positron emission tomography (PET) imaging of herpes simplex virus type 1 thymidine kinase (HSV-tk) gene expression. C6 rat glioma cells with and without the HSV-tk gene were incubated with

  15. Prevalence and clinical consequences of herpes simplex virus type 1 DNA in human cornea tissues

    NARCIS (Netherlands)

    L. Remeijer (Lies); R. Duan (Rui); J.M. van Dun (Jessica); M.A.W. Bettink; A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George)

    2009-01-01

    textabstractBackground. We determined the prevalence and clinical consequences of herpes simplex virus (HSV) type 1 (HSV-1), HSV type 2 (HSV-2), and varicella-zoster virus (VZV) in cornea tissues obtained after penetrating keratoplasty (PKP) was performed. Methods. The excised corneas of 83 patients

  16. Hypertrophic herpes simplex simulating anal neoplasia in AIDS patients: report of five cases.

    Science.gov (United States)

    Nadal, Sidney R; Calore, Edenilson E; Manzione, Carmen R; Horta, Sergio C; Ferreira, Aurea F; Almeida, Lis V

    2005-12-01

    Five patients (4 males; mean age, 46.4 years) with painful verrucous perianal lesions caused by herpes simplex virus are described. All patients had had AIDS for a long time and were using highly active antiretroviral therapy. CD4+ counts ranged from 73 to 370/mm3. All lesions were submitted to resection under subdural anesthesia. Histologic examinations revealed epithelial hyperplasia and dense inflammatory process, composed mainly of lymphocytes and plasma cells, extended just to the hypodermis. Immunohistochemistry was positive for herpes simplex virus Type 2 in four patients and for herpes simplex virus Type 1 in one patient, and did not detect human papillomavirus antigens. Three patients had recurrences after 3, 10, and 12 months. Resection was performed on two patients; one had a new recurrence after three months. Oral acyclovir eliminated the lesion in the third patient. The analysis of our patients suggests that herpes simplex virus, Types 1 and 2, may cause verrucous lesions simulating neoplasia in patients with AIDS using antiretroviral therapy.

  17. Herpes simplex virus type 2 infections of the central nervous system

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; Vestergaard, Bent Faber; Wandall, Johan

    2008-01-01

    Herpes simplex virus type 2 (HSV-2) infections of the central nervous system (CNS) are rare with meningitis as the most common clinical presentation. We have investigated the clinical spectrum of CNS infections in 49 adult consecutive patients with HSV-2 genome in the cerebrospinal fluid (CSF). HSV...

  18. Membrane prteins of herpes simplex infected cells. Immunological and biochemical studies

    NARCIS (Netherlands)

    Welling-Wester, Sijtske

    1981-01-01

    As a consequence of infection with herpes simplex virus (HSV), cells exhibit a number of alterations. One of these is expressed as a change in the polypeptide composition of the surface of the infected cells. In this study several methods used for the isolation of these polypeptides expressed on the

  19. Prevalence and clinical consequences of herpes simplex virus type 1 DNA in human cornea tissues

    NARCIS (Netherlands)

    L. Remeijer (Lies); R. Duan (Rui); J.M. van Dun (Jessica); M.A.W. Bettink; A.D.M.E. Osterhaus (Ab); G.M.G.M. Verjans (George)

    2009-01-01

    textabstractBackground. We determined the prevalence and clinical consequences of herpes simplex virus (HSV) type 1 (HSV-1), HSV type 2 (HSV-2), and varicella-zoster virus (VZV) in cornea tissues obtained after penetrating keratoplasty (PKP) was performed. Methods. The excised corneas of 83 patients

  20. Herpes simplex virus infections among rural residents in eastern China

    Directory of Open Access Journals (Sweden)

    Chen Li

    2011-03-01

    Full Text Available Abstract Background Herpes simplex virus (HSV has two types: HSV-1 and HSV-2. Both infect epithelial cells and establish latent infections in neurons causing an infection that persists for life. Information on age- and gender-specific seroprevalence of HSV-1 and HSV-2 is valuable for understanding HSV transmission dynamics and designing population-based prevention and intervention programs for HSV. However, such information is not available for China. Methods Cryopreserved serum samples of all subjects aged 5 to 60 years from two randomly selected rural villages in Zhejiang province in Eastern China who had participated in the China national seroepidemiological survey of hepatitis B virus (HBV infection conducted in 2006 were tested. Seroprevalence of HSV-1 and HSV-2 infections were determined by type-specific IgG antibody tests using an ELISA technique. Their 95% confidence intervals adjusted for the sampling fraction were calculated according to the Clopper-Pearson method. Results A total of 2,141 residents participated in the survey, with a response rate of 82.3%. HSV-1 seroprevalence was 92.0% overall, 89.1% for males and 94.2% for females. HSV-1 seroprevalence was 61.6% among children aged 5-9 years, 90.3% among 25-29 years, and nearly 100% among those aged > = 40 years. HSV-2 seroprevalence was 13.2% overall, 10.5% for males and 15.3% for females. No children aged 5-14 years were HSV-2 positive, and HSV-2 seroprevalence was 7.1% among 15-19 years and peaked at 24.3% among those aged 45-49 years. Neither HSV-1 nor HSV-2 infections were significantly different by gender. About 11.8% of study subjects were co-infected with both types of HSV. Among 549 participating couples, 8.6% were HSV-1 serodiscordant and 11.8% were HSV-2 serodiscordant. No one tested positive for HIV. The overall prevalence of HBsAg was 16.2%, 16.9% for males and 15.4% for females. Conclusions HSV-1 was highly prevalent among all rural residents aged between 5-60 years in

  1. Structural basis for the antibody neutralization of Herpes simplex virus

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Cheng-Chung; Lin, Li-Ling [Academia Sinica, Taipei 115, Taiwan (China); Academia Sinica, Taipei 115, Taiwan (China); Chan, Woan-Eng [Development Center for Biotechnology, New Taipei City 221, Taiwan (China); Ko, Tzu-Ping [Academia Sinica, Taipei 115, Taiwan (China); Academia Sinica, Taipei 115, Taiwan (China); Lai, Jiann-Shiun [Development Center for Biotechnology, New Taipei City 221, Taiwan (China); Ministry of Economic Affairs, Taipei 100, Taiwan (China); Wang, Andrew H.-J., E-mail: ahjwang@gate.sinica.edu.tw [Academia Sinica, Taipei 115, Taiwan (China); Academia Sinica, Taipei 115, Taiwan (China); Taipei Medical University, Taipei 110, Taiwan (China)

    2013-10-01

    The gD–E317-Fab complex crystal revealed the conformational epitope of human mAb E317 on HSV gD, providing a molecular basis for understanding the viral neutralization mechanism. Glycoprotein D (gD) of Herpes simplex virus (HSV) binds to a host cell surface receptor, which is required to trigger membrane fusion for virion entry into the host cell. gD has become a validated anti-HSV target for therapeutic antibody development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was previously raised against HSV gD for viral neutralization. To understand the structural basis of antibody neutralization, crystals of the gD ectodomain bound to the E317 Fab domain were obtained. The structure of the complex reveals that E317 interacts with gD mainly through the heavy chain, which covers a large area for epitope recognition on gD, with a flexible N-terminal and C-terminal conformation. The epitope core structure maps to the external surface of gD, corresponding to the binding sites of two receptors, herpesvirus entry mediator (HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the gD–nectin-1 interface and occludes the HVEM contact site of gD to block its binding to either receptor. The binding of E317 to gD also prohibits the formation of the N-terminal hairpin of gD for HVEM recognition. The major E317-binding site on gD overlaps with either the nectin-1-binding residues or the neutralizing antigenic sites identified thus far (Tyr38, Asp215, Arg222 and Phe223). The epitopes of gD for E317 binding are highly conserved between two types of human herpesvirus (HSV-1 and HSV-2). This study enables the virus-neutralizing epitopes to be correlated with the receptor-binding regions. The results further strengthen the previously demonstrated therapeutic and diagnostic potential of the E317 antibody.

  2. Surgical excision for recurrent herpes simplex virus 2 (HSV-2) anogenital infection in a patient with human immunodeficiency virus (HIV).

    Science.gov (United States)

    Arinze, Folasade; Shaver, Aaron; Raffanti, Stephen

    2017-05-15

    Recurrent anogenital herpes simplex virus infections are common in patients with human immunodeficiency virus (HIV), of whom approximately 5% develop resistance to acyclovir. We present a case of a 49-year-old man with HIV who had an 8-year history of recurrent left inguinal herpes simplex virus type 2 ulcerations. He initially responded to oral acyclovir, but developed resistance to acyclovir and eventually foscarnet. The lesion progressed to a large hypertrophic mass that required surgical excision, which led to resolution without recurrences. Our case highlights the importance of surgical excision as a treatment option in refractory herpes simplex virus anogenital infections.

  3. Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents.

    Science.gov (United States)

    Tsatsos, Michael; MacGregor, Cheryl; Athanasiadis, Ioannis; Moschos, Marilita M; Hossain, Parwez; Anderson, David

    2016-12-01

    Ophthalmic herpes simplex viral keratitis is responsible for a range of ocular manifestations from superficial epithelial disease to stromal keratitis and endotheliitis. The Herpetic Eye Disease Study has guided the management of herpetic eye disease for almost twenty years, but newer medications such as valacyclovir are now available and are considered to have better bioavailability than acyclovir. In this review, we examine the existing evidence on the pathogenesis of different ophthalmic herpes simplex viral keratitis disease modalities and the role of oral and topically administered antiviral drugs in the treatment of herpes simplex viral keratitis.

  4. The etiology of idiopathic sudden sensorineural hearing loss - Experimental herpes simplex virus infections of the inner ear

    NARCIS (Netherlands)

    Stokroos, RJ; Albers, FWJ; Schirm, J

    Hypothesis: Experimentally induced herpes simplex virus type 1 (HSV-1) labyrinthitis provides a suitable model for idiopathic sudden sensorineural hearing loss (ISSHL). Background: Viral labyrinthitis has been postulated to play a role in the pathophysiology of ISSHL. Circumstantial evidence is

  5. Validity of the coding for herpes simplex encephalitis in the Danish National Patient Registry

    DEFF Research Database (Denmark)

    Jørgensen, Laura Krogh; Dalgaard, Lars Skov; Østergaard, Lars Jørgen

    2016-01-01

    BACKGROUND: Large health care databases are a valuable source of infectious disease epidemiology if diagnoses are valid. The aim of this study was to investigate the accuracy of the recorded diagnosis coding of herpes simplex encephalitis (HSE) in the Danish National Patient Registry (DNPR...... (7.3%) as probable cases providing an overall PPV of 58.0% (95% confidence interval [CI]: 53.0-62.9). For "Encephalitis due to herpes simplex virus" (ICD-10 code B00.4), the PPV was 56.6% (95% CI: 51.1-62.0). Similarly, the PPV for "Meningoencephalitis due to herpes simplex virus" (ICD-10 code B00.4A......) was 56.8% (95% CI: 39.5-72.9). "Herpes viral encephalitis" (ICD-10 code G05.1E) had a PPV of 75.9% (95% CI: 56.5-89.7), thereby representing the highest PPV. The estimated sensitivity was 95.5%. CONCLUSION: The PPVs of the ICD-10 diagnosis coding for adult HSE in the DNPR were relatively low. Hence...

  6. An Unusual Presentationof Herpes Simplex Virus Type 1Infection in a Child

    Directory of Open Access Journals (Sweden)

    Hale Sakallı

    2013-02-01

    Full Text Available We describe an 11-year-old girl presenting with lichen simplex chronicus (LSC and acute bilateral carpal tunnel syndrome (CTS following herpes simplex virus type 1 (HSV-1 infection as evidenced by serological data and by detection of HSV-1 DNA in the blood with the use of PCR. Based on the literature search, this case represents the first childhood case of LSC and acute bilateral CTS following HSV-1 infection. The experience with this patient emphasizes the importance of serological tests and PCR as well as the other laboratory techniques for the accurate diagnosis and management of the disease.

  7. Herpes simplex Virus Esophagitis in an Immunocompetent Patient with Ebstein-Barr Virus Infection

    Directory of Open Access Journals (Sweden)

    M. Tzouvala

    2008-11-01

    Full Text Available Epstein-Barr virus infectious mononucleosis can cause transient immune deficiency which may predispose to reactivation of latent herpes simplex virus (HSV infection in the immunocompetent host. We report the case of a 15-year-old male who presented with severe odynophagia and herpes labialis during the course of Epstein-Barr virus infectious mononucleosis that had been diagnosed ten days before. Esophagoscopy revealed extensive ulcerations with distinct borders and whitish exudates at the mid and distal esophagus. Polymerase chain reaction detected HSV-1 DNA in the biopsy specimens. The patient was treated with intravenous acyclovir. The symptoms resolved rapidly within 3 days, in accordance with improved endoscopic findings.

  8. Synthetic analogues of bovine bactenecin dodecapeptide reduce herpes simplex virus type 2 infectivity in mice

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Shestakov, Andrey; Hancock, Robert E. W

    2013-01-01

    We have evaluated the potential of four synthetic peptides (denoted HH-2, 1002, 1006, 1018) with a distant relationship to the host defense peptide bovine bactenecin dodecapeptide for their ability to prevent genital infections with herpes simplex virus type 2 (HSV-2) in mice. All four peptides...... infectious doses of HSV-2. These data show that peptides HH-2 and 1018 have antiviral properties and can be used to prevent genital herpes infection in mice. (C) 2013 Elsevier B.V. All rights reserved....

  9. Angiogenesis inhibition using an oncolytic herpes simplex virus expressing endostatin in a murine lung cancer model.

    Science.gov (United States)

    Goodwin, Jonathan M; Schmitt, Anthony D; McGinn, Christopher M; Fuchs, Bryan C; Kuruppu, Darshini; Tanabe, Kenneth K; Lanuti, Michael

    2012-03-01

    Herpes-mediated viral oncolysis alone is not sufficient to completely eradicate tumors. In this study we used a replication conditional, endostatin-expressing herpes simplex virus-1 mutant (HSV-Endo) in a murine lung cancer model. We hypothesized that the anti-angiogenic action of endostatin would improve upon the oncolytic effect of HSV-1. HSV-Endo was evaluated in a pulmonary metastases and orthotopic flank model, where there was significantly less tumor burden and reduced microvessel density compared to a control virus. Endostatin expression appears to improve the anti-tumor effect of HSV-1 in a lung cancer model.

  10. Virion component of herpes simplex virus type 1 KOS interferes with early shutoff of host protein synthesis induced by herpes simplex virus type 2 186.

    OpenAIRE

    Hill, T M; Sadler, J R; Betz, J L

    1985-01-01

    Herpes simplex virus (HSV) strains HSV type 1 (HSV-1) KOS and HSV-2 186 are representative of delayed and early shutoff strains, respectively, with regard to their ability to inhibit protein synthesis in Friend erythroleukemia cells. When these cells were simultaneously infected with HSV-1 KOS and HSV-2 186, HSV-1 KOS interfered with the rapid suppression of globin synthesis induced by HSV-2 186. The observed interference was competitive and not due to exclusion of HSV-2 by HSV-1 at the level...

  11. Penile herpes simplex virus type 1 infection presenting two and a half years after Jewish ritual circumcision of an infant.

    Science.gov (United States)

    Yossepowitch, Orit; Gottesman, Tamar; Schwartz, Orna; Stein, Michal; Serour, Francis; Dan, Michael

    2013-06-01

    The association between Jewish ritual circumcision and genital herpes simplex virus type 1 infection has been well described. We report a case of genital herpes that first presented at the age of 2½ years. We believe that the infection was acquired asymptomatically through direct orogenital suction performed during circumcision in the newborn period.

  12. Gene expression of herpes simplex virus. II. Uv radiological analysis of viral transcription units

    Energy Technology Data Exchange (ETDEWEB)

    Millette, R. L.; Klaiber, R.

    1980-06-01

    The transcriptional organization of the genome of herpes simplex virus type 1 was analyzed by measuring the sensitivity of viral polypeptide synthesis to uv irradiation of the infecting virus. Herpes simplex virus type 1 was irradiated with various doses of uv light and used to infect xeroderma pigmentosum fibroblasts. Immediate early transcription units were analyzed by having cycloheximide present throughout the period of infection, removing the drug at 8 h postinfection, and pulse-labeling proteins with (355)methionine. Delayed early transcription units were analyzed in similar studies by having 9-beta-D-arabinofuranosyladenine present during the experiment to block replication of the input irradiated genome. The results indicate that none of the immediate early genes analyzed can be cotranscribed, whereas some of the delayed early genes might be cotranscribed. No evidence was found for the existence of large, multigene transcription units.

  13. Herpes simplex virus-mediated human hypoxanthine-guanine phosphoribosyltransferase gene transfer into neuronal cells.

    Science.gov (United States)

    Palella, T D; Silverman, L J; Schroll, C T; Homa, F L; Levine, M; Kelley, W N

    1988-01-01

    The virtually complete deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) results in a devastating neurological disease, Lesch-Nyhan syndrome. Transfer of the HPRT gene into fibroblasts and lymphoblasts in vitro and into hematopoietic cells in vivo has been accomplished by other groups with retroviral-derived vectors. It appears to be necessary, however, to transfer the HPRT gene into neuronal cells to correct the neurological dysfunction of this disorder. The neurotropic virus herpes simplex virus type 1 has features that make it suitable for use as a vector to transfer the HPRT gene into neuronal tissue. This report describes the isolation of an HPRT-deficient rat neuroma cell line, designated B103-4C, and the construction of a recombinant herpes simplex virus type 1 that contained human HPRT cDNA. These recombinant viruses were used to infect B103-4C cells. Infected cells expressed HPRT activity which was human in origin.

  14. Herpes simplex virus-mediated human hypoxanthine-guanine phosphoribosyltransferase gene transfer into neuronal cells

    Energy Technology Data Exchange (ETDEWEB)

    Palella, T.D.; Silverman, L.J.; Schroll, C.T.; Homa, F.L.; Levine, M.; Kelley, W.N.

    1988-01-01

    The virtually complete deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) results in a devastating neurological disease, Lesch-Nyhan syndrome. Transfer of the HPRT gene into fibroblasts and lymphoblasts in vitro and into hematopoietic cells in vivo has been accomplished by other groups with retroviral-derived vectors. It appears to be necessary, however, to transfer the HPRT gene into neuronal cells to correct the neurological dysfunction of this disorder. The neurotropic virus herpes simplex virus type 1 has features that make it suitable for use as a vector to transfer the HPRT gene into neuronal tissue. This report describes the isolation of an HPRT-deficient rat neuroma cell line, designated B103-4C, and the construction of a recombinant herpes simplex virus type 1 that contained human HPRT cDNA. These recombinant viruses were used to infect B103-4C cells. Infected cells expressed HPRT activity which was human in origin.

  15. Feasibility of herpes simplex virus type 1 mutants labeled with radionuclides for tumor treatment

    Institute of Scientific and Technical Information of China (English)

    Yan-Xia Mi; Ya-Hong Long; Yun-Chun Li

    2008-01-01

    For over one hundred years,viruses have been recognized as capable of killing tumor cells.At present,people are still researching and constructing more suitable oncolytic viruses for treating different malignant tumors.Although extensive studies have demonstrated that herpes simplex virus type 1 (HSV-1) is the most potential oncolytic virus,therapies based on herpes simplex virus type 1 vectors still arouse bio-safety and risk management issues.Researchers have therefore introduced the new idea of treating cancer with HSV-1 mutants labeled with radionuclides,combining radionuclide and oncolytic virus therapies.This overview briefly summarizes the status and mechanisms by which oncolytic viruses kill tumor cells,discusses the application of HSV-1 and HSV-1 derived vectors for tumor therapy,and demonstrates the feasibility and prospect of HSV-1 mutants labeled with radionuclides for treating tumors.

  16. Oncolytic virotherapy using herpes simplex virus: how far have we come?

    Directory of Open Access Journals (Sweden)

    Sokolowski NAS

    2015-11-01

    Full Text Available Nicolas AS Sokolowski,1 Helen Rizos,2 Russell J Diefenbach1 1Centre for Virus Research, Westmead Millennium Institute for Medical Research, The University of Sydney, 2Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia Abstract: Oncolytic virotherapy exploits the properties of human viruses to naturally cause cytolysis of cancer cells. The human pathogen herpes simplex virus (HSV has proven particularly amenable for use in oncolytic virotherapy. The relative safety of HSV coupled with extensive knowledge on how HSV interacts with the host has provided a platform for manipulating HSV to enhance the targeting and killing of human cancer cells. This has culminated in the approval of talimogene laherparepvec for the treatment of melanoma. This review focuses on the development of HSV as an oncolytic virus and where the field is likely to head in the future. Keywords: herpes simplex virus, cancer, immunity, combination therapy, oncolysis

  17. Which plant for which skin disease? Part 1: Atopic dermatitis, psoriasis, acne, condyloma and herpes simplex.

    Science.gov (United States)

    Reuter, Juliane; Wölfle, Ute; Weckesser, Steffi; Schempp, Christoph

    2010-10-01

    Plant extracts and isolated compounds are increasingly used in cosmetics and food supplements to improve skin conditions. We first introduce the positive plant monographs with dermatological relevance of the former German Commission E. Subsequently clinical studies with botanicals for atopic dermatitis, psoriasis, acne, condylomata acuminata and herpes simplex are discussed. The best studies have been conducted with atopic dermatitis and psoriasis patients. Mahonia aquifolium, Hypericum perforatum, Glycyrrhiza glabra and certain traditional Chinese therapies have been shown to be effective in the treatment of atopic dermatitis. Mahonia aquifolium, Indigo naturalis and Capsicum frutescens are effective treatments for psoriasis. Green tea extract and tea tree oil have been investigated in the treatment of acne. Podophyllin and green tea extract are effective treatments for condylomata acuminata. Balm mint and a combination of sage and rhubarb have been shown to be effective in the treatment of herpes simplex in proof of concept studies.

  18. Calcium spirulan derived from Spirulina platensis inhibits herpes simplex virus 1 attachment to human keratinocytes and protects against herpes labialis.

    Science.gov (United States)

    Mader, Julia; Gallo, Antonio; Schommartz, Tim; Handke, Wiebke; Nagel, Claus-Henning; Günther, Patrick; Brune, Wolfram; Reich, Kristian

    2016-01-01

    Chronic infections with herpes simplex virus (HSV) type 1 are highly prevalent in populations worldwide and cause recurrent oral lesions in up to 40% of infected subjects. We investigated the antiviral activity of a defined Spirulina platensis microalga extract and of purified calcium spirulan (Ca-SP), a sulfated polysaccharide contained therein. The inhibitory effects of HSV-1 were assessed by using a plaque reduction assay and quantitative PCR in a susceptible mammalian epithelial cell line and confirmed in human keratinocytes. Time-of-addition and attachment experiments and fluorescence detection of the HSV-1 tegument protein VP16 were used to analyze the mechanism of HSV-1 inhibition. Effects of Ca-SP on Kaposi sarcoma-associated herpesvirus/human herpes virus 8 replication and uptake of the ORF45 tegument protein were tested in human retinal pigment epithelial cells. In an observational trial the prophylactic effects of topically applied Ca-SP were compared with those of systemic and topical nucleoside analogues in 198 volunteers with recurrent herpes labialis receiving permanent lip makeup. Ca-SP inhibited HSV-1 infection in vitro with a potency at least comparable to that of acyclovir by blocking viral attachment and penetration into host cells. Ca-SP also inhibited entry of Kaposi sarcoma-associated herpesvirus/human herpes virus 8. In the clinical model of herpes exacerbation, the prophylactic effect of a Ca-SP and microalgae extract containing cream was superior to that of acyclovir cream. These data indicate a potential clinical use of Ca-SP containing Spirulina species extract for the prophylactic treatment of herpes labialis and suggest possible activity of Ca-SP against infections caused by other herpesviruses. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. Alexia without either agraphia or hemianopia in temporal lobe lesion due to herpes simplex encephalitis.

    Science.gov (United States)

    Erdem, S; Kansu, T

    1995-06-01

    We report a case of alexia without either agraphia or hemianopia following herpes simplex encephalitis. The patient had a temporal lobe lesion with involvement of the occipitotemporal gyrus. This is an unusual cause of alexia without agraphia. The location of the lesion supports the view that transcallosal fibers from the right hemisphere to the left angular gyrus course inferior to the posterior horn of the left lateral ventricle and pass close to the left occipitotemporal gyrus.

  20. Recent advances in vaccine development for herpes simplex virus types I and II

    OpenAIRE

    Coleman, Jeffrey L.; Shukla, Deepak

    2013-01-01

    Despite recent advances in vaccine design and strategies, latent infection with herpes simplex virus (HSV) remains a formidable challenge. Approaches involving live-attenuated viruses and inactivated viral preparations were popular throughout the twentieth century. In the past ten years, many vaccine types, both prophylactic or therapeutic, have contained a replication-defective HSV, viral DNA or glycoproteins. New research focused on the mechanism of immune evasion by the virus has involved ...

  1. Herpes simplex virus type 1 ribonucleotide reductase null mutants induce lesions in guinea pigs.

    Science.gov (United States)

    Turk, S R; Kik, N A; Birch, G M; Chiego, D J; Shipman, C

    1989-12-01

    Two herpes simplex virus type 1 ribonucleotide reductase null mutants, hrR3 and ICP6 delta, produced cutaneous lesions in guinea pigs as severe as those of wild-type strains. The lesions induced by hrR3 resulted from in vivo replication of the mutant virus, suggesting that this virus-encoded enzyme is nonessential for virus replication in guinea pigs.

  2. Contributions of herpes simplex virus type 1 envelope proteins to entry by endocytosis

    Science.gov (United States)

    Herpes simplex virus (HSV) proteins specifically required for endocytic entry but not direct penetration have not been identified. HSVs deleted of gE, gG, gI, gJ, gM, UL45, or Us9 entered cells via either pH-dependent or pH-independent endocytosis and were inactivated by mildly acidic pH. Thus, the ...

  3. Topical and systemic therapies for oral and perioral herpes simplex virus infections.

    Science.gov (United States)

    Stoopler, Eric T; Balasubramaniam, Ramesh

    2013-04-01

    Oral and perioral herpes simplex virus (HSV) infections in healthy individuals often present with signs and symptoms that are clearly recognized by oral health care providers (OHCPs). Management of these infections is dependent upon a variety of factors and several agents may be used for treatment to accelerate healing and decrease symptoms associated with lesions. This article will review the pertinent aspects of topical and systemic therapies of HSV infections for the OHCP.

  4. Possible Neonatal Herpes Simplex Virus (HSV) Acquired Postpartum from Maternal Oral HSV Reactivation after Neuraxial Morphine.

    Science.gov (United States)

    De Guzman, M Cecilia; Chawla, Rupesh; Duttchen, Kaylene

    2014-05-01

    In this report, we describe a case of a neonatal oral herpes simplex virus (HSV) infection possibly acquired from a mother who had oral HSV reactivation in association with neuraxial morphine. Neuraxial morphine is commonly administered for postpartum analgesia after cesarean delivery. While there is evidence that neuraxial morphine increases the risks of oral HSV reactivation in parturients, there has been no report of neonatal HSV infection directly acquired from a mother who had HSV recurrence from neuraxial morphine.

  5. Epidermodysplasia verruciformis with Hansen′s disease, herpes simplex labialis and multiple eccrine hidradenoma

    Directory of Open Access Journals (Sweden)

    Padmavathy L

    2009-01-01

    Full Text Available Epidermodysplasia verruciformis (EV - a rare, lifelong heritable disease due to a unique susceptibility to human papilloma virus. The disseminated verrucous lesions or pityriasis versicolor like lesions persist from early childhood and can transform into a cutaneous malignancy in a fourth of patients. The association of EV with multiple eccrine hidradenoma, herpes simplex labialis and Hansen′s disease is a very rare occurrence and is reported in a 25-year-old woman.

  6. Susceptibility of human iris stromal cells to herpes simplex virus 1 entry.

    Science.gov (United States)

    Baldwin, John; Park, Paul J; Zanotti, Brian; Maus, Erika; Volin, Michael V; Shukla, Deepak; Tiwari, Vaibhav

    2013-04-01

    Ocular herpes simplex virus 1 (HSV-1) infection can lead to multiple complications, including iritis, an inflammation of the iris. Here, we use human iris stroma cells as a novel in vitro model to demonstrate HSV-1 entry and the inflammatory mediators that can damage the iris. The upregulated cytokines observed in this study provide a new understanding of the intrinsic immune mechanisms that can contribute to the onset of iritis.

  7. Effect of the extract of Annona muricata and Petunia nyctaginiflora on Herpes simplex virus.

    Science.gov (United States)

    Padma, P; Pramod, N P; Thyagarajan, S P; Khosa, R L

    1998-05-01

    Annona muricata (Annonaceae) and Petunia nyctaginiflora (Solanaceae) were screened for their activity against Herpes simplex virus-1 (HSV-1) and clinical isolate (obtained from the human keratitis lesion). We have looked at the ability of extract(s) to inhibit the cytopathic effect of HSV-1 on vero cells as indicative of anti-HSV-1 potential. The minimum inhibitory concentration of ethanolic extract of A. muricata and aqueous extract of P. nyctaginiflora was found to be 1 mg/ml.

  8. Computed Tomography Perfusion Usefulness in Early Imaging Diagnosis of Herpes Simplex Virus Encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Marco de Lucas, E.; Mandly, Gonzalez A.; Gutierrez, A.; Sanchez, E.; Arnaiz, J.; Piedra, T.; Rodriguez, E.; Diez, C. [Hospital Univ. Marques de Valdecilla, Santander (Spain). Depts. of Radiology and Neurology

    2006-10-15

    An early diagnosis is crucial in herpes simplex virus encephalitis patients in order to institute acyclovir therapy and reduce mortality rates. Magnetic resonance imaging (MRI) is considered the gold standard for evaluation of these patients, but is frequently not available in the emergency setting. We report the first case of a computed tomography (CT) perfusion study that helped to establish a prompt diagnosis revealing abnormal increase of blood flow in the affected temporoparietal cortex at an early stage.

  9. The identities and anti-herpes simplex virus activity of Clinacanthus nutans and Clinacanthus siamensis

    OpenAIRE

    Paween Kunsorn; Nijsiri Ruangrungsi; Vimolmas Lipipun; Ariya Khanboon; Kanchana Rungsihirunrat

    2013-01-01

    Objective: To distinguish the difference among the Clinacanthus nutans (Burm. f.) Lindau (C. nutans) and Clinacanthus siamensis Bremek (C. siamensis) by assessing pharmacognosy characteristics, molecular aspect and also to evaluate their anti-herpes simplex virus (HSV) type 1 and type 2 activities. Methods: Macroscopic and microscopic evaluation were performed according to WHO Geneva guideline. Stomatal number, stomatal index and palisade ratio of leaves were evaluated. Genomic DNA was ext...

  10. Herpes Simplex Virus Hepatitis in an Immunocompetent Adult: A Fatal Outcome due to Liver Failure

    Directory of Open Access Journals (Sweden)

    Rachel A. Poley

    2011-01-01

    Full Text Available Objective. To present a case of a healthy 41-year-old female who developed fulminant hepatic failure leading to death. The cause of hepatic failure identified on postmortem exam was herpes simplex virus hepatitis. Design. Observation of a single patient. Setting. Intensive care unit of a tertiary care university teaching hospital in Canada. Patient. 41-year-old previously healthy female presenting with a nonspecific viral illness and systemic inflammatory response syndrome. Intervention. The patient was treated with intravenous fluids and broad-spectrum antibiotics. On the second day of admission, she was found to have elevated transaminases, and, over 48 hours, she progressed to fulminant liver failure with disseminated intravascular coagulopathy, refractory lactic acidosis, and shock. She progressed to respiratory failure requiring intubation and mechanical ventilation. She was started on N-acetylcysteine, a bicarbonate infusion, hemodialysis, and multiple vasopressors and inotropes. Measurements and Main Results. Despite treatment, the patient died roughly 70 hours after her initial presentation to hospital. Her postmortem liver biopsy revealed herpes simplex virus hepatitis as her cause of death. Conclusions. Herpes simplex virus must be considered in all patients presenting with liver failure of unknown cause. If suspected, prompt treatment with acyclovir should be initiated.

  11. Herpes simplex virus type 1 in peptic ulcer disease: An inverse association with Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Klisthenis Tsamakidis; Efstathia Panotopoulou; Dimitrios Dimitroulopoulos; Dimitrios Xinopoulos; Maria Christodoulou; Alexandra Papadokostopoulou; Ioannis Karagiannis; Elias Kouroumalis; Emmanuel Paraskevas

    2005-01-01

    AIM: To assess the frequency of herpes simplex virus type Ⅰ in upper gastrointestinal tract ulcers and normal mucosa with the modern and better assays and also with a larger number of well characterized patients and controls and its relationship to Helicobacter pylori(H pylori).METHODS: Biopsy specimens from 90 patients (34 with gastric ulcer of the prepyloric area and 56 with duodenal ulcer) were evaluated. Biopsies from 50 patients with endoscopically healthy mucosa were considered as the control group. The method used to identify herpes simplex virus-1 (HSV-1) was polymerase chain reaction.H pylori was detected by the CLO-test and by histological method.RESULTS: Herpes simplex virus-1 was detected in 28 of 90 patients with peptic ulcer (31%) [11 of 34 patients with gastric ulcer (32.4%) and 17 of 56 with duodenal ulcer (30.4%)] exclusively close to the ulcerous lesion.All control group samples were negative for HSV-1.The likelihood of H pylori negativity among peptic ulcer patients was significantly higher in HSV-1 positive cases than in HSV-1 negative cases (P = 0.009). Gastric ulcer patients with HSV-1 positivity were Strongly associated with an increased possibility of Helicobacter pylori negativity compared to duodenal ulcer patients (P= 0.010).CONCLUSION: HSV-1 is frequent in upper gastrointestinal tract ulcers but not in normal gastric and duodenal mucosa. There is an inverse association between HSV-1 and H pylori infection.

  12. Herpes Simplex Vaccines: Prospects of Live-attenuated HSV Vaccines to Combat Genital and Ocular infections

    Science.gov (United States)

    Stanfield, Brent; Kousoulas, Konstantin Gus

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) and its closely related type-2 (HSV-2) viruses cause important clinical manifestations in humans including acute ocular disease and genital infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no vaccines available against herpes simplex viral infections. However, a number of promising vaccine approaches are being explored in pre-clinical investigations with few progressing to early phase clinical trials. Consensus research findings suggest that robust humoral and cellular immune responses may partially control the frequency of reactivation episodes and reduce clinical symptoms. Live-attenuated viral vaccines have long been considered as a viable option for generating robust and protective immune responses against viral pathogens. Varicella zoster virus (VZV) belongs to the same alphaherpesvirus subfamily with herpes simplex viruses. A live-attenuated VZV vaccine has been extensively used in a prophylactic and therapeutic approach to combat primary and recurrent VZV infection indicating that a similar vaccine approach may be feasible for HSVs. In this review, we summarize pre-clinical approaches to HSV vaccine development and current efforts to test certain vaccine approaches in human clinical trials. Also, we discuss the potential advantages of using a safe, live-attenuated HSV-1 vaccine strain to protect against both HSV-1 and HSV-2 infections. PMID:27114893

  13. Case of herpes simplex encephalitis(HSE) with a thalamic lesion

    Energy Technology Data Exchange (ETDEWEB)

    Fujimori, K.; Koike, R.; Yuasa, T.; Miyatake, T.; Ito, J.

    1987-02-01

    A case of herpes simplex encephalitis (HSE) with thalamic involvement was reported. The patient, a 27-year-old man, was admitted because of abnormal behavior and fever. He exhibited a disturbance of consciousness, meningial signs, and hyperreflexia. A CT scan of the head revealed diffuse brain edema. Acute encephalitis, especially HSE, was suspected, and so the intravenous administration of acyclovir and steroid therapy were started. The titer of herpes simplex Type 1 virus, as measured by CF and ELISA, was found to have increased amounts of serum and cerebrospinal fluid. 5 days after the onset, his consciousness worsened. He could not tell his name and scarely opened his eyes upon pain stimulation. A CT scan at this time showed low-density lesions in the left thalamus, cingulate gyrus, and the posterior portion of the putamen. About 5 days later, his consciousness level was increased, but he was mute. This symptom was thought to be thalamic aphasia, which might be correlative with the low-density lesions shown in the left thalamus by the CT scan. About 30 days after the onset of the disease, his speech became normal, and a CT scan at 51 hospital days showed no abnormality. The etiology of low-density lesions of the left thalamus in the CT scan is speculated to be as follows: firstly, vascular damage of circulation disturbance, and secondly a special affinity of herpes simplex Type 1 virus to the thalamus.

  14. Extreme sensitivity of enveloped viruses, including herpes simplex, to long-chain unsaturated monoglycerides and alcohols

    Energy Technology Data Exchange (ETDEWEB)

    Sands, J.; Auperin, D.; Snipes, W.

    1979-01-01

    Unsaturated monoglycerides and alcohols of chain lengths of 16 to 18 carbons were found to be extremely potent inactivators of two enveloped viruses, herpes simplex virus type 2 and bacteriophage phi 6. The lipid-containing bacteriophage PM2 was also inactivated by some of these amphiphilic molecules. Treatment of herpes simplex virus type 2 with these compounds at concentrations as low as 0.2 ..mu..M reduced virus survival to 50% in 30 min, making these agents the most potent inactivators of herpes simplex viruses discovered that are not cytotoxic to mammalian cells. Detailed characterizations of the effects of unsaturated monoglycerides and alcohols on bacteriophages phi 6 and PM2 showed that the inactivated phi 6 virion remained nearly intact but that PM2 was almost completely disrupted by the inactivating treatment. Some of the compounds inactivate the viruses even at low temperature (0/sup 0/C). Excess amounts of diglycerides and phospholipids interfere with the inactivating abilities of some of the unsaturated monoglycerides and alcohols against phi 6 and PM2. Our findings suggest that the unsaturated monoglycerides and some of the unsaturated alcohols should be further studied as potential antiviral agents. Particularly for application to herpesvirus-infected areas of the skin and accessible epithelium.

  15. Chronic ulcerating genital herpes simplex virus infection: A diagnosis mislead by HIV infection

    Directory of Open Access Journals (Sweden)

    Sudip Parajuli

    2014-07-01

    Full Text Available We report a case of chronic herpes simplex in a 27 year old lady presenting with a history of persistent verrucous ulcer in the natal cleft of nine months duration. The patient was diagnosed and treated initially as a case of Tuberculosis Verrucosa Cutis (TVC based on the chronicity of the ulcer, negative HIV serological tests and histopathological findings. The diagnosis had to be revised as the lesion was increasing in size and the patient was not responding to treatment even after completing antituberculous treatment for six months. Repeat histopathological examination and immunohistochemistry showed DNA of herpes simplex. Based on this finding a repeat HIV serology was sent which was positive. The ulcer healed after a course of acyclovir. The case is being reported to highlight the importance of considering chronic herpes simplex infection in a case of chronic genital ulcer. In addition this case reminds us the nature of HIV infection to mislead the diagnosis by altering the natural course of the disease process.

  16. Valaciclovir versus aciclovir for the treatment of primary genital herpes simplex: a cost analysis.

    Science.gov (United States)

    Pinder, Melissa; Wright, Alison

    2015-11-01

    The current guidelines for the treatment of primary herpes simplex in the Genito-urinary department in Sheffield Teaching Hospitals NHS Foundation Trust, recommend valaciclovir as a first-line medication. This is a prodrug of aciclovir, which has been used for many years as a treatment for primary herpes simplex virus. The basis of the recommendation largely relates to valaciclovir being more bioavailable than aciclovir. However, there is no evidence to suggest this has an effect on overall outcome with regard to symptom control and viral shedding. The purpose of the service evaluation was to discover if significant cost savings could be made by changing the prescribing policy to make aciclovir the drug of choice for primary herpes simplex virus. Based on 160 patients receiving valaciclovir (500 mg BD) during April 2013 and March 2014, if they had been treated with aciclovir (400 mg TDS) instead, a saving of £828.80 (66% reduction) could have been made.

  17. Diagnosis of Herpes Simplex Encephalitis by ELISA Using Antipeptide Antibodies Against Type-Common Epitopes of Glycoprotein B of Herpes Simplex Viruses.

    Science.gov (United States)

    Bhullar, Shradha S; Chandak, Nitin H; Baheti, Neeraj N; Purohit, Hemant J; Taori, Girdhar M; Daginawala, Hatim F; Kashyap, Rajpal S

    2016-01-01

    Herpes simplex encephalitis (HSE) represents one of the most severe infectious diseases of the central nervous system (CNS). As effective antiviral drugs are available, an early, rapid, and reliable diagnosis has become important. The objective of this article was to develop a sensitive ELISA protocol for herpes simplex viruses (HSV) antigen detection and quantitation by assessing the usefulness of antipeptide antibodies against potential peptides of HSV glycoprotein B (gB). A total of 180 cerebrospinal fluid (CSF) samples of HSE and non-HSE patients were analyzed using a panel of antipeptide antibodies against synthetic peptides of HSV glycoprotein gB. The cases of confirmed and suspected HSE showed 80% and 51% positivity for antipeptide against synthetic peptide QLHDLRF and 77% and 53% positivity for antipeptide against synthetic peptide MKALYPLTT, respectively for the detection of HSV antigen in CSF. The concentration of HSV antigen was found to be higher in confirmed HSE as compared to suspected HSE group and the viral load correlated well with antigen concentration obtained using the two antipeptides in CSF of confirmed HSE group. This is the first article describing the use of antibodies obtained against synthetic peptides derived from HSV in diagnostics of HSE using patients' CSF samples.

  18. Oral herpes simplex virus infection in pregnancy: what are the concerns?

    Science.gov (United States)

    Ficarra, Giuseppe; Birek, Catalena

    2009-09-01

    Although epidemiologic data and the potentially serious effects of transmission of genital herpes from mother to infant during birth have been widely reported, published reports on oral herpes disease in pregnancy remain scarce and no clear management guidelines exist. Thus, questions remain about acquisition, transmission and outcome of infection, especially with respect to acute gingivostomatitis in pregnancy. In response to these questions, we summarize previous reports on herpes simplex virus 1 (HSV-1) oral disease in pregnancy and, briefly, present 2 cases of primary gingivostomatitis in the first trimester of pregnancy, resulting in a favourable outcome for both mother and infant. We also point out the most recent data on rare, potentially severe in outcome, but treatable, primary central nervous system HSV-1 infection in later stages of pregnancy. Finally, we emphasize a multidisciplinary approach to oral HSV disease in pregnancy, with dentist participation in the diagnosis and treatment.

  19. Susceptibility of herpes simplex virus isolated from genital herpes lesions to ASP2151, a novel helicase-primase inhibitor.

    Science.gov (United States)

    Katsumata, Kiyomitsu; Weinberg, Adriana; Chono, Koji; Takakura, Shoji; Kontani, Toru; Suzuki, Hiroshi

    2012-07-01

    ASP2151 (amenamevir) is a helicase-primase inhibitor against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus. To evaluate the anti-HSV activity of ASP2151, susceptibility testing was performed on viruses isolated from patients participating in a placebo- and valacyclovir-controlled proof-of-concept phase II study for recurrent genital herpes. A total of 156 HSV strains were isolated prior to the dosing of patients, and no preexisting variants with less susceptibility to ASP2151 or acyclovir (ACV) were detected. ASP2151 inhibited HSV-1 and HSV-2 replication with mean 50% effective concentrations (EC(50)s) of 0.043 and 0.069 μM, whereas ACV exhibited mean EC(50)s of 2.1 and 3.2 μM, respectively. Notably, the susceptibilities of HSV isolates to ASP2151 and ACV were not altered after dosing with the antiviral agents. Taken together, these results demonstrate that ASP2151 inhibits the replication of HSV clinical isolates more potently than ACV, and HSV resistant to this novel helicase-primase inhibitor as well as ACV may not easily emerge in short-term treatment for recurrent genital herpes patients.

  20. Leflunomide in the Treatment of a Pseudotumoral Genital Herpes Simplex Virus Infection in an HIV Patient.

    Science.gov (United States)

    Roger, Marie R; Anstead, Gregory M

    2017-01-01

    The patient is a 52-year-old African American man with a past medical history of HIV infection (on antiretroviral therapy, CD4 count 399 cells/µL, and undetectable HIV viral load) and recurrent genital herpes. While on valacyclovir, the patient presented with four tumorous lesions on the perineum and scrotum. A biopsy specimen stained positively with HSV-1 and HSV-2 immunostains and displayed a lymphoplasmacytic infiltrate. The patient received foscarnet and imiquimod for two weeks with minimal improvement. Based on the previous activity of leflunomide, which has both antiviral and immunomodulatory properties, in cytomegalovirus and herpes simplex infections, leflunomide 20 mg orally twice daily was started. The patient received 23 days of foscarnet, 14 days of topical imiquimod, and 11 days of leflunomide with approximately 80% reduction in the size of the perineal lesion. After nine months on leflunomide there was complete regression of the large perineal lesion and only two small ulcerations remained on the scrotum. Pseudotumoral herpes lesions in HIV patients represent an immune reconstitution event and are poorly responsive to the usual anti-herpes agents. This report demonstrates the successful use of leflunomide in the treatment of an HIV patient with pseudotumoral herpes. Thalidomide has also been used with some success.

  1. Leflunomide in the Treatment of a Pseudotumoral Genital Herpes Simplex Virus Infection in an HIV Patient

    Directory of Open Access Journals (Sweden)

    Marie R. Roger

    2017-01-01

    Full Text Available The patient is a 52-year-old African American man with a past medical history of HIV infection (on antiretroviral therapy, CD4 count 399 cells/µL, and undetectable HIV viral load and recurrent genital herpes. While on valacyclovir, the patient presented with four tumorous lesions on the perineum and scrotum. A biopsy specimen stained positively with HSV-1 and HSV-2 immunostains and displayed a lymphoplasmacytic infiltrate. The patient received foscarnet and imiquimod for two weeks with minimal improvement. Based on the previous activity of leflunomide, which has both antiviral and immunomodulatory properties, in cytomegalovirus and herpes simplex infections, leflunomide 20 mg orally twice daily was started. The patient received 23 days of foscarnet, 14 days of topical imiquimod, and 11 days of leflunomide with approximately 80% reduction in the size of the perineal lesion. After nine months on leflunomide there was complete regression of the large perineal lesion and only two small ulcerations remained on the scrotum. Pseudotumoral herpes lesions in HIV patients represent an immune reconstitution event and are poorly responsive to the usual anti-herpes agents. This report demonstrates the successful use of leflunomide in the treatment of an HIV patient with pseudotumoral herpes. Thalidomide has also been used with some success.

  2. Herpes simplex virus 1 and 2 educational assessment of young adults in rural southwest Virginia.

    Science.gov (United States)

    Hover, Shantal S; Bertke, Andrea S

    2017-01-01

    Herpes simplex virus 2 (HSV-2) causes genital herpes, one of the most common sexually transmitted infections (STIs) in the U.S. HSV-1, commonly associated with cold sores, is increasing as a cause of genital herpes. Abstinence-only sexual health classes, commonly taught in Virginia, generate young adults who are under-educated in sexual health, increasing STI risks. College students in southwest Virginia were surveyed to assess comprehensiveness of high school health education regarding HSV-1 and HSV-2 and to identify students' preferred methods for STI education. To obtain data on knowledge of HSV, comprehensiveness of sexual health education in high school, and preferred learning methods, 237 college students participated in an online questionnaire and 28 students were interviewed using structured interviews. Questionnaire and interview data indicated that Family Life Education classes need to include more comprehensive information on prevention, viral transmission, and differences between HSV-1 and HSV-2. The majority of total respondents (both the questionnaire and interview) (65%) reported non-comprehensive high school sexual health education. The majority of interview (79%) and questionnaire (55%) respondents wished they had learned more about herpes and other STIs in high school. Education preferences of both interviewed and surveyed respondents included interactive internet programs or games, more realistic lectures, and learning about STIs later in high school when students reported greater sexual activity. Our results indicate that more comprehensive sexual health education is needed and wanted by students in southwest Virginia. More relevant educational programs should be implemented for VA high school students utilizing technology and interactive methods to improve student engagement in sexual health education. These studies provide information on knowledge of herpes simplex viruses among college students, comprehensiveness of sexual health education

  3. Validity of the coding for herpes simplex encephalitis in the Danish National Patient Registry

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    Jørgensen LK

    2016-05-01

    Full Text Available Laura Krogh Jørgensen,1 Lars Skov Dalgaard,1 Lars Jørgen Østergaard,1 Nanna Skaarup Andersen,2 Mette Nørgaard,3 Trine Hyrup Mogensen1 1Department of Infectious Diseases, Aarhus University Hospital, Aarhus, 2Department of Clinical Microbiology, Odense University Hospital, Odense, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Background: Large health care databases are a valuable source of infectious disease epidemiology if diagnoses are valid. The aim of this study was to investigate the accuracy of the recorded diagnosis coding of herpes simplex encephalitis (HSE in the Danish National Patient Registry (DNPR. Methods: The DNPR was used to identify all hospitalized patients, aged ≥15 years, with a first-time diagnosis of HSE according to the International Classification of Diseases, tenth revision (ICD-10, from 2004 to 2014. To validate the coding of HSE, we collected data from the Danish Microbiology Database, from departments of clinical microbiology, and from patient medical records. Cases were classified as confirmed, probable, or no evidence of HSE. We estimated the positive predictive value (PPV of the HSE diagnosis coding stratified by diagnosis type, study period, and department type. Furthermore, we estimated the proportion of HSE cases coded with nonspecific ICD-10 codes of viral encephalitis and also the sensitivity of the HSE diagnosis coding. Results: We were able to validate 398 (94.3% of the 422 HSE diagnoses identified via the DNPR. Hereof, 202 (50.8% were classified as confirmed cases and 29 (7.3% as probable cases providing an overall PPV of 58.0% (95% confidence interval [CI]: 53.0–62.9. For “Encephalitis due to herpes simplex virus” (ICD-10 code B00.4, the PPV was 56.6% (95% CI: 51.1–62.0. Similarly, the PPV for “Meningoencephalitis due to herpes simplex virus” (ICD-10 code B00.4A was 56.8% (95% CI: 39.5–72.9. “Herpes viral encephalitis” (ICD-10 code G05.1E had a PPV

  4. Analysis of Herpes Simplex Virus in Suspected Encephalitis, Keratitis and Dermal Infections Using Real- Time PCR

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    Nasrin Aliabadi

    2014-03-01

    Full Text Available Background & Objectives: Herpes viruses can cause diseases in the clinical range. The virus can cause infection in various body parts, especially eyes and nervous system. The aim of this study was at evaluating  the Real-Time TaqMan probe PCR in diagnosing and monitoring of the patients with suspected HSV infections.Materials & Methods: More than a thousand patients with suspected HSV infections were collected. The samples were analyzed by Real-time PCR assays. DNA was extracted according to manufacturer’s instruction (Invisorb Spin Virus DNA mini Kit, Germany. The Real-Time PCR assay was performed with the primer Design TM genesis for herpes simplex virus (Primer Design, UK.  Results: Total of 44 (5.6%, 118 (26.8%, 23(11.7%, 13 (5.6 % and 65(45.5% patients out of  herpes simplex encephalitis suspected group, HSK suspected, patients with suspected systemic HSV infection, HSV skin suspected ones and oropharyngeal HSV infection suspected patients respectively were found to be positive by Real-time PCR assays..Conclusion: As indicated by the results, Real-time PCR assay, with high sensitivity and specificity, can help in early diagnosis. The viral load obtained by this method, can be the best marker in a person for following the therapeutic effect.

  5. Attachment and penetration of acyclovir-resistant herpes simplex virus are inhibited by Melissa officinalis extract.

    Science.gov (United States)

    Astani, Akram; Navid, Mojdeh Heidary; Schnitzler, Paul

    2014-10-01

    Medicinal plants are increasingly of interest as novel source of drugs for antiherpetic agents, because herpes simplex virus (HSV) might develop resistance to commonly used antiviral drugs. An aqueous extract of Melissa officinalis and the phenolic compounds caffeic acid, p-coumaric acid and rosmarinic acid were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) acyclovir-sensitive and clinical isolates of acyclovir-resistant strains in vitro. When drugs were added during the intracellular replication of HSV-1 infected cells, no antiviral effect was observed by plaque reduction assay. However, Melissa extract interacted directly with free viral particles of two acyclovir-resistant HSV strains at low IC50 values of 0.13 and 0.23 µg/mL and high selectivity indices of 2692 and 1522, respectively. The Melissa extract and rosmarinic acid inhibited HSV-1 attachment to host cells in a dose-dependent manner for acyclovir-sensitive and acyclovir-resistant strains. These results indicate that mainly rosmarinic acid contributed to the antiviral activity of Melissa extract. Penetration of herpes viruses into cells was inhibited by Melissa extract at 80% and 96% for drug-sensitive and drug-resistant viruses, respectively. Melissa extract exhibits low toxicity and affects attachment and penetration of acyclovir-sensitive and acyclovir-resistant HSVs in vitro. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Treatment of herpes simplex labialis with low power laser therapy.

    Directory of Open Access Journals (Sweden)

    Bianka M. González

    2009-11-01

    Full Text Available Introducción: El herpes simple es causado por Herpes virus hominis, que produce una afección eruptiva aguda de uno o más grupos de vesículas sobre una base eritematosa; puede localizarse en cualquier parte del cuerpo preferentemente en la boca y los genitales precedida y acompañada de ardor y prurito. Objetivos: Se evaluó la efectividad del tratamiento con láser de baja potencia en relación al tratamiento convencional según la evolución clínica, desaparición de síntomas y signos en los pacientes con herpes simple labial. Metodología: La muestra comprendió 60 pacientes que asistieron a la consulta de dermatología por dicha entidad, en cuatro policlínicos de la capital cubana en el transcurso del año 2006. Se llevó a cabo un estudio explicativo de tipo experimental y prospectivo, donde se aplicaron dos tipos de tratamientos, el convencional con aciclovir por vía oral y tópica y el láser de baja potencia, como único tratamiento. Resultados: Hubo predominio del sexo femenino con 78.3%; el grupo de edad más afectado estaba entre 28 y 37 años (45.5%, la media del número de sesiones necesarias para la desaparición de síntomas y signos en el tratamiento convencional fue 7.3 sesiones mientras que en el tratamiento con láser fue 5.2 sesiones y se pudo evidenciar que sí existen diferencias estadísticamente significativas entre las medias de ambos tratamientos; en cuanto a la evolución clínica ambos tratamientos tuvieron mayor porcentaje de pacientes curados. Se recomienda evaluar a largo plazo la presencia de recidivas y que se utilice esta técnica como una opción de tratamiento para mejorar la calidad de vida de los pacientes afectados.

  7. Physical mapping of the herpes simplex virus type 2 nuc- lesion affecting alkaline exonuclease activity by using herpes simplex virus type 1 deletion clones.

    Science.gov (United States)

    Wathen, M W; Hay, J

    1984-07-01

    The nuc- lesion affecting alkaline exonuclease activity in the herpes simplex virus type 2 (HSV-2) mutant ts1348 had previously been mapped to the EcoRI-D restriction enzyme fragment of HSV-1. Eight clones with deletions representing most of HSV-1 EcoRI fragment D were selected with lambda gtWES hybrids. These clones were tested for their ability to rescue the alkaline exonuclease activity of HSV-2 nuc- ts1348 virus. The sequences colinear with the HSV-2 nuc- lesion were found to map between 0.169 and 0.174 map units on the HSV-1 Patton genome, representing an 0.8-kilobase-pair region that is 12.9 to 13.7 kilobase pairs from the left end of HSV-1 EcoRI fragment D.

  8. Herpes simplex virus infection in pregnancy and in neonate: status of art of epidemiology, diagnosis, therapy and prevention

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    Barucca Valentina

    2009-04-01

    Full Text Available Abstract Herpes simplex virus (HSV infection is one of the most common viral sexually transmitted diseases worldwide. The first time infection of the mother may lead to severe illness in pregnancy and may be associated with virus transmission from mother to foetus/newborn. Since the incidence of this sexually transmitted infection continues to rise and because the greatest incidence of herpes simplex virus infections occur in women of reproductive age, the risk of maternal transmission of the virus to the foetus or neonate has become a major health concern. On these purposes the Authors of this review looked for the medical literature and pertinent publications to define the status of art regarding the epidemiology, the diagnosis, the therapy and the prevention of HSV in pregnant women and neonate. Special emphasis is placed upon the importance of genital herpes simplex virus infection in pregnancy and on the its prevention to avoid neonatal HSV infections.

  9. Eritema multiforme ampollar extenso asociado a infección por virus herpes simplex Extended Bullous Erythema Multiforme Associated To Herpes Simplex Virus Infection

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    A Elgueta-Noy

    2009-12-01

    Full Text Available El Eritema Multiforme (EM es una reacción cutánea aguda generalmente benigna y autolimitada, asociada a la infección por Virus Herpes Simplex (HSV. Se caracteriza por lesiones polimorfas y tipo diana en extremidades y mucosas. Presentamos un paciente de 22 años con pápulas, vesículas y ampollas, que evoluciona con un 90% de la superficie corporal comprometida en tres semanas. Se realizó una reacción de polimerasa en cadena para HSV, resultando positiva en una costra. La biopsia de piel y la tinción de inmunohistoquímica positiva para linfocitos T CD4, fueron compatibles con EM ampollar asociado a HSV. Destacamos la importancia de la correlación clínico patológica, apoyada por el estudio virológico, en el diagnóstico de este caso de presentación atípica. Los hallazgos de laboratorio confirmaron lo descrito en la literatura respecto de la patogenia del EM asociado a HSV.Erythema Multiforme (EM is a generally benign and self-limited acute cutaneous reaction, associated with Herpes Simplex Virus (HSV infection. It is characterized by polymorphic "target" lesions in extremities and mucosal tissues. We report a 22-year old patient with papules, vesicles and blisters, which evolved to cover 90% of the body in three weeks. We performed a PCR study for HSV, which was positive in a crust. A skin biopsy and positive immunohistochemical stain for LT CD4+ were compatible with bullous EM associated with HSV. We underline the importance of pathological clinical correlation, reinforced by a virological study, in the diagnosis of this case with atypical symptoms. The laboratory findings confirmed literature descriptions with respect to the pathogenicity of EM associated with HSV.

  10. Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review

    Directory of Open Access Journals (Sweden)

    Nebel Almut

    2010-01-01

    Full Text Available Abstract Apolipoprotein E is a polymorphic and multifunctional protein with numerous roles in lipoprotein metabolism. The three common isoforms apoE2, apoE3 and apoE4 show isoform-specific functional properties including different susceptibilities to diseases. ApoE4 is an accepted risk factor for Alzheimer's disease and cardiovascular disorders. Recently, associations between apoE4 and infectious diseases have been demonstrated. This review summarises how apoE4 may be involved in the infection incidence and associated pathologies of specific infectious diseases, namely hepatitis C, human immunodeficiency virus disease and herpes simplex. ApoE4 seems to be protective against chronic hepatitis C virus infection and retards fibrosis progression. In contrast apoE4 enhances the fusion rate of human immunodeficiency virus with target cell membranes, resulting in accelerated cell entry and faster disease progression. Its association with human immunodeficiency virus-associated dementia remains controversial. Regarding herpes simplex virus infection, apoE4 intensifies virus latency and is associated with increased oxidative damage of the central nervous system, and there is some evidence that herpes simplex virus infection in combination with the apoE4 genotype may be associated with an increased risk of Alzheimer's disease. In addition to reviewing available data from human trials, evidence derived from a variety of cell culture and animal models are considered in this review in order to provide mechanistic insights into observed association between apoE4 genotype and viral disease infection and pathology.

  11. The Challenges and Opportunities for Development of a T-Cell Epitope-Based Herpes Simplex Vaccine

    Science.gov (United States)

    Kuo, Tiffany; Wang, Christine; Badakhshan, Tina; Chilukuri, Sravya; BenMohamed, Lbachir

    2014-01-01

    The infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a half billion individuals worldwide. HSV-2 infections cause painful genital herpes, encephalitis, and death in newborns. HSV-1 infections are more prevalent than HSV-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. While genital herpes in mainly caused by HSV-2 infections, in recent years, there is an increase in the proportion of genital herpes caused by HSV-1 infections in young adults, which reach 50% in some western societies. While prophylactic and therapeutic HSV vaccines remain urgently needed for centuries their development has been notoriously difficult. During the most recent National Institute of Health (NIH) workshop titled "Next Generation Herpes Simplex Virus Vaccines: The Challenges and Opportunities", basic researchers, funding agencies, and pharmaceutical representatives gathered: (i) to assess the status of herpes vaccine research; and (ii) to identify the gaps and propose alternative approaches in developing a safe and efficient herpes vaccine. One “common denominator” among previously failed clinical herpes vaccine trials is that they either used a whole virus or whole viral proteins, which contain both pathogenic “symptomatic” and protective “asymptomatic” antigens/epitopes. In this report, we continue to advocate that using an “asymptomatic” epitope-based vaccine strategy that selectively incorporates protective epitopes which: (i) are exclusively recognized, in vitro, by effector memory CD4+ and CD8+ TEM cells from “naturally” protected seropositive asymptomatic individuals; and (ii) protect, in vivo, human leukocyte antigen (HLA) transgenic animal models from ocular and genital herpes infections and diseases, could be the answer to many of the scientific challenges facing HSV vaccine

  12. Social Stress and the Reactivation of Latent Herpes Simplex Virus Type 1

    Science.gov (United States)

    Padgett, David A.; Sheridan, John F.; Dorne, Julianne; Berntson, Gary G.; Candelora, Jessica; Glaser, Ronald

    1998-06-01

    Psychological stress is thought to contribute to reactivation of latent herpes simplex virus (HSV). Although several animal models have been developed in an effort to reproduce different pathogenic aspects of HSV keratitis or labialis, until now, no good animal model existed in which application of a psychological laboratory stressor results in reliable reactivation of the virus. Reported herein, disruption of the social hierarchy within colonies of mice increased aggression among cohorts, activated the hypothalamic-pituitary-adrenal axis, and caused reactivation of latent HSV type 1 in greater than 40% of latently infected animals. However, activation of the hypothalamic-pituitary-adrenal axis using restraint stress did not activate the latent virus. Thus, the use of social stress in mice provides a good model in which to investigate the neuroendocrine mechanisms that underlie behaviorally mediated reactivation of latent herpes-viruses.

  13. Spectroscopic investigation of herpes simplex viruses infected cells and their response to antiviral therapy

    Science.gov (United States)

    Erukhimovitch, Vitaly; Talyshinsky, Marina; Souprun, Yelena; Huleihel, Mahmoud

    2006-07-01

    In the present study, we used microscopic Fourier transform infrared spectroscopy (FTIR) to evaluate the antiviral activity of known antiviral agents against herpes viruses. The antiviral activity of Caffeic acid phenethyl ester (CAPE) (which is an active compound of propolis) against herpes simplex type 1 and 2 was examined in cell culture. The advantage of microscopic FTIR spectroscopy over conventional FTIR spectroscopy is that it facilitates inspection of restricted regions of cell culture or tissue. Our results showed significant spectral differences at early stages of infection between infected and non-infected cells, and between infected cells treated with the used antiviral agent and those not treated. In infected cells, there was a considerable increase in phosphate levels. Our results show that treatment with used antiviral agent considerably abolish the spectral changes induced by the viral infection. In addition, it is possible to track by FTIR microscopy method the deferential effect of various doses of the drug.

  14. Cellular Players in the Herpes Simplex Virus Dependent Apoptosis Balancing Act

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    John A. Blaho

    2009-11-01

    Full Text Available Apoptosis is triggered as an intrinsic defense against numerous viral infections. Almost every virus encodes apoptotic modulators, and the herpes simplex viruses (HSV are no exception. During HSV infection, there is an intricate balance between pro- and anti-apoptotic factors that delays apoptotic death until the virus has replicated. Perturbations in the apoptotic balance can cause premature cell death and have the potential to dramatically alter the outcome of infection. Recently, certain cellular genes have been shown to regulate sensitivity to HSV-dependent apoptosis. This review summarizes current knowledge of the cellular genes that impact the apoptotic balance during HSV infection.

  15. Activation and Evasion of Innate Antiviral Immunity by Herpes Simplex Virus

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    Søren R. Paludan

    2009-11-01

    Full Text Available Herpes simplex virus (HSV, a human pathogenic virus, has evolved several strategies to evade the production and function of interferons (IFNs and cytokines generated by the innate immune system to restrict the virus. Equilibrium exists between the virus and the immune response, and a shift in this delicate balance either restricts the virus or enhances virus spread and tissue damage. Therefore, understanding of the cytokine response generated after HSV infection and the underlying virus-cell interactions is essential to improve our understanding of viral pathogenesis. This review summarizes the current knowledge on induction and evasion of the innate immune response by HSV.

  16. Conjunctival geographic ulcer: an overlooked sign of herpes simplex virus infection.

    Science.gov (United States)

    Hung, Jia-Horung; Chu, Chang-Yao; Lee, Chaw-Ning; Hsu, Chao-Kai; Lee, Julia Yu-Yun; Wang, Jen-Ren; Chang, Kung-Chao; Huang, Fu-Chin

    2015-03-01

    Herpes simplex virus (HSV) ocular infection causes significant visual burden worldwide. Despite the fact that dendritic or geographic corneal ulcers are typical findings in HSV epithelial keratitis, conjunctival ulcer as a sign of HSV infection has rarely been reported. Although easily overlooked, this important sign could be enhanced by fluorescein staining. We report two cases of conjunctival geographic ulcers proven to be HSV infection by viral isolation and polymerase chain reaction (PCR). One patient had bilateral disease and blepharitis, and the other had unilateral involvement without skin lesions. With timely diagnosis and proper management, excellent visual outcome can be expected.

  17. Optimization of Substitution Matrix for Sequence Alignment of Major Capsid Proteins of Human Herpes Simplex Virus

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    Vipan Kumar Sohpal

    2011-12-01

    Full Text Available Protein sequence alignment has become an informative tool in modern molecular biology research. A number of substitution matrices have been readily available for sequence alignments, but it is challenging task to compute optimal matrices for alignment accuracy. Here, we used the parameter optimization procedure to select the optimal Q of substitution matrices for major viral capsid protein of human herpes simplex virus. Results predict that Blosum matrix is most accurate on alignment benchmarks, and Blosum 60 provides the optimal Q in all substitution matrices. PAM 200 matrices results slightly below than Blosum 60, while VTML matrices are intermediate of PAM and VT matrices under dynamic programming.

  18. Dense amnesia in a professional musician following herpes simplex virus encephalitis.

    Science.gov (United States)

    Wilson, B A; Baddeley, A D; Kapur, N

    1995-10-01

    We describe the memory functioning of C, a professional musician who became amnesic following herpes simplex encephalitis in 1985. Although transient amnesia in a professional musician has previously been described, this is the first reported case of chronic amnesia in a highly talented professional musician. C is unusual in three respects. First, his amnesia is particularly severe. Second, his amnesia includes semantic as well as episodic memory deficits. Third, he believes he has just woken up and his preoccupation with this state of 'just wakening' has persisted for over 9 years. This appears to be the result of a delusion rather than the consequence of his amnesia.

  19. Oral mucosal diseases in the office setting--part I: Aphthous stomatitis and herpes simplex infections.

    Science.gov (United States)

    Sciubba, James J

    2007-01-01

    This article is an update and review of the most common nontraumatic ulcerative and vesicular lesions of the oral cavity. Details concerning their etiology, pathogenesis, clinical presentation, differential diagnosis, and management are included. Comparisons are made between the various forms of aphthous ulcerations and their viral counterparts. Lesions of herpes simplex origin are described for both primary and recurrent or secondary forms and differentiation from aphthous ulcerations is made. Treatment options for both the chronic and more acute forms of this condition are discussed.

  20. Herpes simplex virus 1 counteracts viperin via its virion host shutoff protein UL41.

    Science.gov (United States)

    Shen, Guanghui; Wang, Kezhen; Wang, Shuai; Cai, Mingsheng; Li, Mei-li; Zheng, Chunfu

    2014-10-01

    The interferon (IFN)-inducible viperin protein restricts a broad range of viruses. However, whether viperin plays a role during herpes simplex virus 1 (HSV-1) infection is poorly understood. In the present study, it was shown for the first time that wild-type (WT) HSV-1 infection couldn't induce viperin production, and ectopically expressed viperin inhibited the replication of UL41-null HSV-1 but not WT viruses. The underlying molecular mechanism is that UL41 counteracts viperin's antiviral activity by reducing its mRNA accumulation.

  1. Seroepidemiology of Herpes Simplex Virus Type 1 and 2 in Anzali city 2010-2011

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    Sara Rezaei-Chaparpordi

    2012-08-01

    Full Text Available Background: Objective of this study was to determine the seroprevalence of herpes simplex virus type 1 and 2 in Anzali city for the first time. Materials and Methods: 200 persons selected randomely and demographic data gathered. HSV-1, 2 and HSV-2 ELISA kits used to determine IgG type specific antibodies.Results: HSV-1 and HSV-2 IgG antibodies were positive in 131 (65.5% and 7(3.5% subjects. Conclusion: HSV-1 Was more prevalent than HSV-2 and seropositivity increased with age

  2. Herpes simplex virus type 1 and type 2 in the Netherlands : seroprevalence, risk factors and changes during a 12-year period

    NARCIS (Netherlands)

    Woestenberg, Petra J; Tjhie, Jeroen H T; de Melker, Hester E; van der Klis, Fiona R M; van Bergen, Jan E A M; van der Sande, Marianne A B; van Benthem, Birgit H B

    2016-01-01

    BACKGROUND: Genital herpes results in considerable morbidity, including risk of neonatal herpes, and is increasingly being caused by Herpes Simplex Virus (HSV) type 1. Possibly children are less often HSV-1 infected, leaving them susceptible until sexual debut. We assessed changes in the Dutch HSV-1

  3. Radioimmunoassay for herpes simplex virus (HSV) thymidine kinase

    Energy Technology Data Exchange (ETDEWEB)

    McGuirt, P.V.; Keller, P.M.; Elion, G.B.

    1982-01-30

    A sensitive RIA for HSV-1 thymidine kinase (TK) has been developed. This assay is based on competition for the binding site of a rabbit antibody against purified HSV-1 TK, between a purified /sup 3/H-labeled HSV-1 TK and a sample containing an unknown amount of viral TK. The assay is capable of detecting 8 ng or more of the HSV enzyme. Purified HSV-1 TK denatured to <1% of its original kinase activity is as effective in binding to the antibody as is native HSV-1 TK. Viral TK is detectable at ranges of 150-460 ng/mg protein of cell extract from infected cells or cells transformed by HSV or HSV genetic material. HSV-2 TK appears highly cross-reactive, VZV TK is slightly less so, and the vaccinia TK shows little or no cross-reactivity. This RIA may serve as a tool for monitoring the expression of the HSV TK during an active herpes virus infection, a latent ganglionic infection, or in neoplastic cells which may have arisen by viral transformation.

  4. Genital Herpes

    Science.gov (United States)

    Genital herpes is a sexually transmitted disease (STD) caused by a herpes simplex virus (HSV). It can cause sores on ... also infect their babies during childbirth. Symptoms of herpes are called outbreaks. You usually get sores near ...

  5. Herpes simplex type 2 encephalitis and methotrexate medication: a fortuitous or causative association in a patient with spondyloarthritis?

    Science.gov (United States)

    Lupo, Julien; Dos Santos, Ophélie; Germi, Raphaele; Baccard-Longère, Monique; Stahl, Jean-Paul; Epaulard, Olivier; Morand, Patrice

    2016-11-23

    It is unclear whether immunosuppression is a risk factor for herpes encephalitis. Herein, we describe a rare case of herpes simplex virus (HSV) type 2 encephalitis in a patient treated with low-dose methotrexate for HLA-B27-associated spondyloarthritis. The patient was successfully treated with acyclovir but presented sequelae of encephalitis. Here we discuss the possible role of low-dose MTX therapy as a risk factor of neurological herpes reactivation and severe disease. The host-related and viral risk factors are also addressed.

  6. Seroepidemiology of Rubella, Cytomegalovirus, Herpes simplex & Varicella zoster virus in college women of Bushehr.

    Directory of Open Access Journals (Sweden)

    Afshin Barazesh

    2014-01-01

    Full Text Available Abstract Background: Acute viral infections such as cytomegalovirus, Rubella, Herpes simplex and varicella zoster virus in pregnant women can cause congenital infection with increased risk of developing congenital anomalies and morbidity. We aimed to identify young women susceptible to these viral infections in Bushehr. Materials and Methods: In 2009, 180 female were randomly selected from high schools and college students who were been assisted in marriage consulting clinics. In this cross sectional study, IgG antibodies against varicella zoster virus (VZV, Herpes simplex virus I,II (HSV I,II , Rubella & cytomegalovirus (CMV were determined by indirect enzyme immunoassay (ELISA technique. Results: Mean age of the participants was 18.72 years old. %99.4 and %95 of sera were positive for cytomegalovirus & Rubella respectively and also Antibodies against VZV & HSV were detected in %74.5 & %69.4 of samples. There were no significant correlation between antibody seropositivity and education level, living places (rural or urban and occupation. (P<0/05. Conclusion: Although, The findings of this study indicated that high prevalence rate of VZV &HSV 1,2 in child bearing age women, but 1/3 -1/4 of them, are still susceptible to these infections, so routine screening of these viruses is suggested in antenatal care.

  7. Melissa officinalis extract inhibits attachment of herpes simplex virus in vitro.

    Science.gov (United States)

    Astani, Akram; Reichling, Jürgen; Schnitzler, Paul

    2012-01-01

    Extracts and essential oils of medicinal plants are increasingly of interest as novel drugs for antiherpetic agents, since the herpes simplex virus (HSV) might develop resistance to commonly used antiviral drugs. An aqueous extract of Melissa officinalis as well as phenolic extract compounds, i.e. caffeic acid, p-coumaric acid and rosmarinic acid were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. When drugs were added to HSV-1-infected cells, no antiviral effect was observed as determined by plaque reduction assay and analysis of expression of viral protein ICP0. However, the Melissa extract demonstrated a high virucidal activity against HSV-1, even at very low concentrations of 1.5 μg/ml, whereas similar results for phenolic compounds were only achieved at 100 times higher concentrations. Besides the virucidal activity, the Melissa extract and rosmarinic acid inhibited HSV-1 attachment to host cells in a dose-dependent manner. These results indicate that rosmarinic acid was the main contributor to the antiviral activity of Melissa extract. However, the selectivity index of Melissa extract of 875 against HSV is superior to the selectivity indices of single constituents. Melissa extract exhibits low toxicity, is virucidal and affects HSV-1 attachment to host cells in vitro. Copyright © 2012 S. Karger AG, Basel.

  8. Rad51 and Rad52 are involved in homologous recombination of replicating herpes simplex virus DNA.

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    Ka-Wei Tang

    Full Text Available Replication of herpes simplex virus 1 is coupled to recombination, but the molecular mechanisms underlying this process are poorly characterized. The role of Rad51 and Rad52 recombinases in viral recombination was examined in human fibroblast cells 1BR.3.N (wild type and in GM16097 with replication defects caused by mutations in DNA ligase I. Intermolecular recombination between viruses, tsS and tsK, harboring genetic markers gave rise to ∼17% recombinants in both cell lines. Knock-down of Rad51 and Rad52 by siRNA reduced production of recombinants to 11% and 5%, respectively, in wild type cells and to 3% and 5%, respectively, in GM16097 cells. The results indicate a specific role for Rad51 and Rad52 in recombination of replicating herpes simplex virus 1 DNA. Mixed infections using clinical isolates with restriction enzyme polymorphisms in the US4 and US7 genes revealed recombination frequencies of 0.7%/kbp in wild type cells and 4%/kbp in GM16097 cells. Finally, tandem repeats in the US7 gene remained stable upon serial passage, indicating a high fidelity of recombination in infected cells.

  9. Antiviral activity of mycosynthesized silver nanoparticles against herpes simplex virus and human parainfluenza virus type 3

    Directory of Open Access Journals (Sweden)

    Gaikwad S

    2013-11-01

    Full Text Available Swapnil Gaikwad,1 Avinash Ingle,1 Aniket Gade,1 Mahendra Rai,1 Annarita Falanga,3 Novella Incoronato,2 Luigi Russo,2 Stefania Galdiero,3 Massimilano Galdiero2 1Department of Biotechnology, Sant Gadge Baba Amravati University, Amravati, Maharashtra, India; 2Department of Experimental Medicine, Division of Microbiology, II University of Naples, 3Department of Pharmacy, University of Naples “Federico II”, DFM and Institute of Biostructures and Bioimages, Naples, Italy Abstract: The interaction between silver nanoparticles and viruses is attracting great interest due to the potential antiviral activity of these particles, and is the subject of much research effort in the treatment of infectious diseases. In this work, we demonstrate that silver nanoparticles undergo a size-dependent interaction with herpes simplex virus types 1 and 2 and with human parainfluenza virus type 3. We show that production of silver nanoparticles from different fungi is feasible, and their antiviral activity is dependent on the production system used. Silver nanoparticles are capable of reducing viral infectivity, probably by blocking interaction of the virus with the cell, which might depend on the size and zeta potential of the silver nanoparticles. Smaller-sized nanoparticles were able to inhibit the infectivity of the viruses analyzed. Keywords: silver nanoparticles, antiviral, herpes simplex virus, parainfluenza virus

  10. Striated muscle involvement in experimental oral infection by herpes simplex virus type 1.

    Science.gov (United States)

    Gonzalez, María Inés; Sanjuan, Norberto A

    2013-07-01

    Herpes simplex virus type 1 is one of the most frequent causes of oral infection in humans, especially during early childhood. Several experimental models have been developed to study the pathogenesis of this virus but all of them employed adult animals. In this work, we developed an experimental model that uses mice younger than 4 days old, to more closely resemble human infection. Mice were infected subcutaneously with the prototype strain McIntyre of Herpes simplex-1, and the progression of infection was studied by immunoperoxidase. All animals died within 24-72 h post-infection, while viral antigens were found in the oral epithelium, nerves and brain. The most striking result was the finding of viral antigens in the nucleus and cytoplasm of cells belonging to striated muscles. Organotypic cultures of striated muscles were performed, and viral replication was observed in them by immunocytochemistry, electron microscopy and viral isolation. We conclude that the infection of striated muscles is present from the onset of oral infection and, eventually, could explain some clinical observations in humans.

  11. Specific Inhibition of Herpes Simplex Virus DNA Polymerase by Helical Peptides Corresponding to the Subunit Interface

    Science.gov (United States)

    Digard, Paul; Williams, Kevin P.; Hensley, Preston; Brooks, Ian S.; Dahl, Charles E.; Coen, Donald M.

    1995-02-01

    The herpes simplex virus DNA polymerase consists of two subunits-a catalytic subunit and an accessory subunit, UL42, that increases processivity. Mutations affecting the extreme C terminus of the catalytic subunit specifically disrupt subunit interactions and ablate virus replication, suggesting that new antiviral drugs could be rationally designed to interfere with polymerase heterodimerization. To aid design, we performed circular dichroism (CD) spectroscopy and analytical ultracentrifugation studies, which revealed that a 36-residue peptide corresponding to the C terminus of the catalytic subunit folds into a monomeric structure with partial α-helical character. CD studies of shorter peptides were consistent with a model where two separate regions of α-helix interact to form a hairpin-like structure. The 36-residue peptide and a shorter peptide corresponding to the C-terminal 18 residues blocked UL42-dependent long-chain DNA synthesis at concentrations that had no effect on synthesis by the catalytic subunit alone or by calf thymus DNA polymerase δ and its processivity factor. These peptides, therefore, represent a class of specific inhibitors of herpes simplex virus DNA polymerase that act by blocking accessory-subunit-dependent synthesis. These peptides or their structures may form the basis for the synthesis of clinically effective drugs.

  12. Disparities in herpes simplex virus type 2 infection between black and white men who have sex with men in Atlanta, GA.

    Science.gov (United States)

    Okafor, Netochukwu; Rosenberg, Eli S; Luisi, Nicole; Sanchez, Travis; del Rio, Carlos; Sullivan, Patrick S; Kelley, Colleen F

    2015-09-01

    HIV disproportionately affects black men who have sex with men, and herpes simplex virus type 2 is known to increase acquisition of HIV. However, data on racial disparities in herpes simplex virus type 2 prevalence and risk factors are limited among men who have sex with men in the United States. InvolveMENt was a cohort study of black and white HIV-negative men who have sex with men in Atlanta, GA. Univariate and multivariate cross-sectional associations with herpes simplex virus type 2 seroprevalence were assessed among 455 HIV-negative men who have sex with men for demographic, behavioural and social determinant risk factors using logistic regression. Seroprevalence of herpes simplex virus type 2 was 23% (48/211) for black and 16% (38/244) for white men who have sex with men (p = 0.05). Education, poverty, drug/alcohol use, incarceration, circumcision, unprotected anal intercourse, and condom use were not associated with herpes simplex virus type 2. In multivariate analyses, black race for those ≤25 years, but not >25 years, and number of sexual partners were significantly associated. Young black men who have sex with men are disproportionately affected by herpes simplex virus type 2, which may contribute to disparities in HIV acquisition. An extensive assessment of risk factors did not explain this disparity in herpes simplex virus type 2 infection suggesting differences in susceptibility or partner characteristics. © The Author(s) 2014.

  13. The etiology of idiopathic sudden sensorineural hearing loss - Experimental herpes simplex virus infections of the inner ear

    NARCIS (Netherlands)

    Stokroos, RJ; Albers, FWJ; Schirm, J

    1998-01-01

    Hypothesis: Experimentally induced herpes simplex virus type 1 (HSV-1) labyrinthitis provides a suitable model for idiopathic sudden sensorineural hearing loss (ISSHL). Background: Viral labyrinthitis has been postulated to play a role in the pathophysiology of ISSHL. Circumstantial evidence is pain

  14. Quantification of viral DNA and liver enzymes in plasma improves early diagnosis and management of herpes simplex virus hepatitis

    NARCIS (Netherlands)

    M.F.C. Beersma (Thijs); G.M.G.M. Verjans (George); H.J. Metselaar (Herold); A.D.M.E. Osterhaus (Albert); W.R. Berrington; G.J.J. van Doornum (Gerard)

    2011-01-01

    textabstractHerpes simplex virus (HSV) hepatitis is a rare and potential life-threatening disease. The diagnosis of HSV hepatitis is hampered by its indifferent clinical presentation, which necessitates confirmatory laboratory data to identify HSV in the affected liver. However, liver biopsies are o

  15. Long Term Neuropsychological Follow-Up in Patients With Herpes Simplex Encephalitis and Predominantly Left-Sided Lesions

    Directory of Open Access Journals (Sweden)

    B. Laurent

    1991-01-01

    Full Text Available Five patients with predominantly dominant cerebral hemisphere lesions due to herpes simplex encephalitis are described. Verbal amnesia was the main deficit but amnesic aphasia sometimes associated with impairment of remote memory also occurred. Semantic and episodic memory deficits were also explored in one case and the role of the right cerebral hemisphere in facilitating recovery of learning is discussed.

  16. Quantification of viral DNA and liver enzymes in plasma improves early diagnosis and management of herpes simplex virus hepatitis

    NARCIS (Netherlands)

    M.F.C. Beersma (Thijs); G.M.G.M. Verjans (George); H.J. Metselaar (Herold); A.D.M.E. Osterhaus (Albert); W.R. Berrington; G.J.J. van Doornum (Gerard)

    2011-01-01

    textabstractHerpes simplex virus (HSV) hepatitis is a rare and potential life-threatening disease. The diagnosis of HSV hepatitis is hampered by its indifferent clinical presentation, which necessitates confirmatory laboratory data to identify HSV in the affected liver. However, liver biopsies are

  17. Evaluation of new transport medium for detection of herpes simplex virus by culture and direct enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Ogburn, J R; Hoffpauir, J T; Cole, E; Hood, K; Michael, D; Nguyen, T; Raden, S; Raju, B; Reisinger, V; Oefinger, P E

    1994-12-01

    The transport medium Multi-Microbe Media (M4) was evaluated prospectively by culture and direct enzyme-linked immunosorbent assay (ELISA) for detection of herpes simplex virus from 473 specimens. In addition, 377 specimens in Bartels Viral Transport Medium were evaluated. By using culture as a "gold standard," the ELISA sensitivity was approximately 85%, while the specificities exceeded 96% for both media.

  18. Longitudinal study on oral shedding of herpes simplex virus 1 and varicella-zoster virus in individuals infected with HIV

    NARCIS (Netherlands)

    M. van Velzen (Monique); W.J.D. Ouwendijk (Werner ); S. Selke (Stacy); S.D. Pas (Suzan); F.B. van Loenen (Freek); A.D.M.E. Osterhaus (Albert); A. Wald (Anna); G.M.G.M. Verjans (George)

    2013-01-01

    textabstractPrimary herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) infection leads to a life-long latent infection of ganglia innervating the oral mucosa. HSV-1 and VZV reactivation is more common in immunocompromised individuals and may result in viral shedding in saliva. We determ

  19. Detection of varicella-zoster virus and herpes simplex virus by the polymerase chain reaction with degenerate primers

    NARCIS (Netherlands)

    Jacobs, J.J.L.; Folkers, E.; Vreeswijk, J.

    1999-01-01

    Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are human pathogens of significance involved in multiple diseases with either typical or atypical clinical features. In neonates and immunocompromised patients these alphaherpesviruses may cause life-threatening diseases such as

  20. [F-18]FHPG positron emission tomography for detection of herpes simplex virus (HSV) in experimental HSV encephalitis

    NARCIS (Netherlands)

    Buursma, AR; de Vries, EFJ; Garssen, J; Kegler, D; van Waarde, A; Schirm, J; Hospers, GAP; Mulder, NH; Vaalburg, W; Klein, HC

    2005-01-01

    Herpes simplex virus type 1 (HSV-1) is one of the most common causes of sporadic encephalitis. The initial clinical course of HSV encephalitis (HSE) is highly variable, and the infection may be rapidly fatal. For effective treatment with antiviral medication, an early diagnosis of HSE is crucial. Su

  1. Herpes simplex virus type 2 induces rapid cell death and functional impairment of murine dendritic cells in vitro

    NARCIS (Netherlands)

    Jones, CA; Fernandez, M; Herc, K; Bosnjak, L; Miranda-Saksena, M; Boadle, RA; Cunningham, A

    2003-01-01

    Dendritic cells (DC) are critical for stimulation of naive T cells. Little is known about the effect of herpes simplex virus type 2 (HSV-2) infection on DC structure or function or if the observed effects of HSV-1 on human DC are reproduced in murine DC. Here, we demonstrate that by 12 h

  2. Anaesthesia For Caesarean Section of Single Umbilical Artery and Herpes Simplex Virus Type 1 Ig M Positive Obstetric Patient

    OpenAIRE

    Gülhaş, Nurçin; Toğal, Türkan; Demirbilek, Semra; Köroğlu, Ahmet; YÜCEL, Aytaç; Ersoy, M. Özcan

    2003-01-01

    Single umbilical artery is associated with multiple organ malformations, fetoplacental insufficiency and intrauterine fetal growth retardation. During anaesthesia severe hypotension can cause decrease of uteroplacental blood flow and fetal distress. Herpes Simplex (HSV) infection is activated by exogeneous factors such as sunlight, wind, trauma and fever or endogenous physcological factors such as stress especially in immune deficiency. The choice of anaesthetic technique for ...

  3. TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice

    DEFF Research Database (Denmark)

    Reinert, Line S; Harder, Louis; Holm, Christian K

    2012-01-01

    Herpes simplex viruses (HSVs) are highly prevalent neurotropic viruses. While they can replicate lytically in cells of the epithelial lineage, causing lesions on mucocutaneous surfaces, HSVs also establish latent infections in neurons, which act as reservoirs of virus for subsequent reactivation ...

  4. Detection of varicella-zoster virus and herpes simplex virus by the polymerase chain reaction with degenerate primers

    NARCIS (Netherlands)

    Jacobs, J.J.L.; Folkers, E.; Vreeswijk, J.

    1999-01-01

    Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are human pathogens of significance involved in multiple diseases with either typical or atypical clinical features. In neonates and immunocompromised patients these alphaherpesviruses may cause life-threatening diseases such as encephaliti

  5. A Strategy for O-Glycoproteomics of Enveloped Viruses-the O-Glycoproteome of Herpes Simplex Virus Type 1

    DEFF Research Database (Denmark)

    Bagdonaite, Ieva; Nordén, Rickard; Joshi, Hiren J

    2015-01-01

    present a novel proteome-wide discovery strategy for O-glycosylation sites on viral envelope proteins using herpes simplex virus type 1 (HSV-1) as a model. We identified 74 O-linked glycosylation sites on 8 out of the 12 HSV-1 envelope proteins. Two of the identified glycosites found in glycoprotein B...

  6. Glycoprotein I of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region

    DEFF Research Database (Denmark)

    Norberg, Peter; Olofsson, Sigvard; Tarp, Mads Agervig

    2007-01-01

    Glycoprotein I (gI) of herpes simplex virus type 1 (HSV-1) contains a tandem repeat (TR) region including the amino acids serine and threonine, residues that can be utilized for O-glycosylation. The length of this TR region was determined for 82 clinical HSV-1 isolates and the results revealed...

  7. Diagnosis of genital herpes simplex virus infection in the clinical laboratory

    Science.gov (United States)

    2014-01-01

    Since the type of herpes simplex virus (HSV) infection affects prognosis and subsequent counseling, type-specific testing to distinguish HSV-1 from HSV-2 is always recommended. Although PCR has been the diagnostic standard method for HSV infections of the central nervous system, until now viral culture has been the test of choice for HSV genital infection. However, HSV PCR, with its consistently and substantially higher rate of HSV detection, could replace viral culture as the gold standard for the diagnosis of genital herpes in people with active mucocutaneous lesions, regardless of anatomic location or viral type. Alternatively, antigen detection—an immunofluorescence test or enzyme immunoassay from samples from symptomatic patients--could be employed, but HSV type determination is of importance. Type-specific serology based on glycoprotein G should be used for detecting asymptomatic individuals but widespread screening for HSV antibodies is not recommended. In conclusion, rapid and accurate laboratory diagnosis of HSV is now become a necessity, given the difficulty in making the clinical diagnosis of HSV, the growing worldwide prevalence of genital herpes and the availability of effective antiviral therapy. PMID:24885431

  8. SEROEPIDEMIOLOGY OF TOXOPLASMA, RUBELLA, CYTOMEGALOVIRUS AND HERPES SIMPLEX VIRUS -2 IN WOMEN WITH BAD OBSTETRIC HISTORY. PART II. CYTOMEGALOVIRUS AND HERPES SIMPLEX VIRUS INFECTIONS

    Directory of Open Access Journals (Sweden)

    Abdulghani Mohamed Alsamarai

    2013-10-01

    Full Text Available Bad obstetric history (BOH is reported worldwide and is associated with social and psychological impacts. Cytomegalovirus and herpes simplex virus play an important role in the induction of adverse outcomes of pregnancy. Highest CMV IgG prevalence rate was reported for India (91.05%, while the lowest rate was reported for Iran (14.28%. Unfortunately, six studies in Iraq reported a high prevalence of CMV IgM in non-married, pregnant and women with BOH. The range of recent CMV infection in pregnant women with BOH was from 1.4% in Jordan to 60.2% in Iraq. In women with BOH, the highest HSV 2 prevalence (16.8% was noted in India, while the lowest rate (1.69% was reported in India also. In Arab countries, among women with BOH, HSV 2 IgG and IgM seroprevalence higher rates were reported for Iraq. This literature review highlights the high bacterial and viral maternal infection rate in the developing world. Urgent, concerted action is required to reduce the burden of these infections. In addition to raising awareness about the severity of the problem of maternal infections in the developing world, data from this review will be beneficial in guiding public health policy, research interests and donor funding towards achieving improvement in health care delivery.

  9. Herpes simplex induced necrotizing tonsillitis in an immunocompromised patient with ulcerative colitis

    Science.gov (United States)

    Jansen, Laura; Vos, Xander G; Löwenberg, Mark

    2016-01-01

    We here present the case of a 22-year-old female of Suriname ethnicity with ulcerative colitis who received treatment with mercaptopurine and infliximab. She presented herself with a severe necrotizing tonsillitis due to herpes simplex virus type-1 (HSV-1). Combination therapy consisting of immunomodulators and anti-tumor necrosis factor (TNF) agents is increasingly being used. Anti-TNF therapy is associated with an increased risk of developing serious infections, and especially patients receiving combination treatment with thiopurines are at an increased risk. We here show that HSV infections can cause a severe tonsillitis in immunocompromised patients. Early recognition is essential when there is no improvement with initial antibiotic therapy within the first 24 to 72 h. HSV infections should be in the differential diagnosis of immunocompromised patients presenting with a necrotizing tonsillitis and can be confirmed by polymerase chain reaction. Early treatment with antiviral agents should be considered especially if antibiotic treatment fails in such patients. PMID:26881193

  10. Latent acyclovir-resistant herpes simplex virus type 1 in trigeminal ganglia of immunocompetent individuals.

    Science.gov (United States)

    van Velzen, Monique; van Loenen, Freek B; Meesters, Roland J W; de Graaf, Miranda; Remeijer, Lies; Luider, Theo M; Osterhaus, Albert D M E; Verjans, Georges M G M

    2012-05-15

    Specific mutations within the hypervariable herpes simplex virus (HSV) gene thymidine kinase (TK) gene lead to acyclovir (ACV) resistance. To uncover the existence of latent ACV-resistant (ACV(R)) HSV-1, we determined the genetic and functional variability of the HSV-1 TK gene pool in paired trigeminal ganglia (TG) of 5 immunocompetent individuals. The latent virus pool consisted of a donor-specific HSV-1 quasispecies, including one major ACV-sensitive (ACV(S)) and multiple phylogenetic-related minor ACV(S) and ACV(R) TK variants. Contrary to minor variants, major TK variants were shared between paired TG. The data demonstrate the coexistence of phylogenetic-related ACV(S) and ACV(R) latent HSV-1 in human TG.

  11. Aciclovir resistance among indian strains of Herpes simplex virus as determined using a dye uptake assay

    Directory of Open Access Journals (Sweden)

    Abraham A

    2007-01-01

    Full Text Available Resistance to aciclovir (ACV among Herpes simplex virus (HSV isolates is increasingly being reported in the literature particularly in immunocompromised patients. However, there is only limited data available from India despite widespread use of ACV in our hospital. A cross-sectional study was hence conducted to determine the aciclovir (ACV susceptibility of HSV 1 and 2 isolates using a dye uptake (DU assay. This study showed a 3.0% prevalence of ACV resistance among HSV-1 strains (2/66, median IC 50 0.098 µg/mL while in HSV-2 strains, it was 7.8% (5/64, median IC 50 0.195 µg/mL. The IC 50 for the HSV-1 and HSV-2 strains resistant to ACV was greater than or equal to 6.25 µg/mL.

  12. The Herpes Simplex Virus Type 1 Multiple Function Protein ICP27

    Institute of Scientific and Technical Information of China (English)

    Lei ZHAO; Wen-bo ZHU; Qiong DING; Gui-qiang PENG; Chun-fu ZHENG

    2008-01-01

    The herpes simplex virus type 1 (HSV-1) infected-cell protein 27 (ICP27) is an essential,highly conserved protein involved in various steps of HSV-1 gene regulation as well as in the shut-off of host gene expression during infection.It functions primarily at the post-transcriptional level in inhibiting precursor mRNA splicing and in promoting nuclear export of viral transcripts.Recently,many novel functions performed by the HSV-1 ICP27 protein were shown,including leptomycin B resistance,inhibition of the type I interferon signaling,regulation of the viral mRNA translation and determining the composition of HSV-1 virions.

  13. A Multiple Functional Protein: the Herpes Simplex Virus Type 1 Tegument Protein VP22

    Institute of Scientific and Technical Information of China (English)

    Mei-li LI; Hong GUO; Qiong DING; Chun-fu ZHENG

    2009-01-01

    The herpes simplex virus type 1 (HSV-1) VP22, is one of the most abundant HSV-1 tegument proteins with an average stoichiometry of 2 400 copies per virion and conserved among alphaherpesvirinae. Many functions are attributed to VP22, including nuclear localization, chromatin binding, microtubule binding, induction of microtubule reorganization, intercellular transport, interaction with cellular proteins, such as template activating factor I (TAF-I) and nonmuscle myosin II A (NMIIA), and viral proteins including tegument protein VP16, pUS9 and pUL46, glycoprotein E (gE) and gD. Recently, many novel functions performed by the HSV-1 VP22 protein have been shown, including promotion of protein synthesis at late times in infection, accumulation of a subset of viral mRNAs at early times in infection and possible transcriptional regulation function.

  14. Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated?

    Science.gov (United States)

    Al-Dujaili, Lena J; Clerkin, Patrick P; Clement, Christian; McFerrin, Harris E; Bhattacharjee, Partha S; Varnell, Emily D; Kaufman, Herbert E; Hill, James M

    2012-01-01

    Most humans are infected with herpes simplex virus (HSV) type 1 in early childhood and remain latently infected throughout life. While most individuals have mild or no symptoms, some will develop destructive HSV keratitis. Ocular infection with HSV-1 and its associated sequelae account for the majority of corneal blindness in industrialized nations. Neuronal latency in the peripheral ganglia is established when transcription of the viral genome is repressed (silenced) except for the latency-associated transcripts and microRNAs. The functions of latency-associated transcripts have been investigated since 1987. Roles have been suggested relating to reactivation, establishment of latency, neuronal protection, antiapoptosis, apoptosis, virulence and asymptomatic shedding. Here, we review HSV-1 latent infections, reactivation, recurrent disease and antiviral therapies for the ocular HSV diseases. PMID:21861620

  15. Status of vaccine research and development of vaccines for herpes simplex virus.

    Science.gov (United States)

    Johnston, Christine; Gottlieb, Sami L; Wald, Anna

    2016-06-03

    Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries.

  16. Herpes Simplex Proctitis Mimicking Inflammatory Bowel Disease in a Teenaged Male

    Directory of Open Access Journals (Sweden)

    Kristen E. Sandgren

    2017-01-01

    Full Text Available We report the case of a 17-year-old male who was initially assessed for pain with defecation, bloody rectal discharge, and diarrhea, consistent with proctitis. Though proctitis is most commonly due to inflammatory bowel disease (IBD, infectious etiologies must also be considered, including sexually transmitted causes of infectious proctitis. In discussion of his sexual history, he identified as homosexual and acknowledged engaging in receptive anal intercourse. Rectal biopsies obtained via colonoscopy were culture-positive for herpes simplex virus (HSV, leading to a diagnosis of HSV proctitis and treatment with an appropriate antiviral medication. HSV proctitis is more common in individuals with high-risk sexual practices, including men who have sex with men. While this may be an uncommon diagnosis for pediatricians to make in practice, a high clinical index of suspicion for sexually transmitted infectious proctitis in those with risk factors must be maintained in order to facilitate appropriate testing, treatment, and counseling of affected individuals.

  17. Synthesis and anti-herpes simplex viral activity of monoglycosyl diglycerides.

    Science.gov (United States)

    Janwitayanuchit, Wicharn; Suwanborirux, Khanit; Patarapanich, Chamnan; Pummangura, Sunibhond; Lipipun, Vimolmas; Vilaivan, Tirayut

    2003-12-01

    Based on the discovery of antiviral beta-galactosyl diglycerides from Clinacanthus nutans leaves, 19 monoglycosyl diglycerides were synthesized and examined for inhibitory effect on herpes simplex virus types 1 and 2 (HSV-1, HSV-2). A study of the structure-activity relationships of the synthetic monoglycosyl diglycerides indicated that the fatty acyl moieties were critical for inhibitory action with higher activity displayed as the acyl groups became more olefinic in character. The sugar moiety was also important for anti-HSV action; however, the type of sugar (glucose or galactose) did not affect activity. The stereochemistry at C-2 of the glycerol backbone displayed no significant effect on anti-HSV activity. Among the compounds synthesized, 1,2-O-dilinolenoyl-3-O-beta-D-glucopyranosyl-sn-glycerol showed the highest inhibitory activity against HSV-1 and HSV-2 with IC50 values of 12.5+/-0.5 and 18.5+/-1.5 microg/ml, respectively.

  18. Electroencephalographic and computed X-ray tomographic findings in 99 Japanese cases of herpes simplex encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Satoshi; Takasu, Toshiaki; Tamura, Masato; Otani, Sugishi.

    1988-10-01

    This is a retrospective analysis of electroencephalograms (EEG) and computed tomograms (CT) obtained from 99 Japanese patients with herpes simplex encephalitis (HSE). Abnormal findings of EEG were seen in 89 patients (99 %). Focal abnormality, which was frequently detected in the first EEG recording, was seen in 68 patients (76 %). Periodic synchronous discharge was observed in 25 patients (28 %). There were abnormal findings on CT in 88 patients (81 %). Low and high density areas were seen in 64 patients (73 %) and 26 patients (37 %), respectively, with the most frequent site being the temporal lobe. Mass effect was demonstrated in 33 patients (37 %). Electroencephalography detected the abnormal findings earlier than CT during the early stage of HSE in many instances. There was concordance between EEG and CT in the detection of HSE lesions in 45 patients (58 %). (Namekawa, K.).

  19. Case of herpes simplex encephalitis without neurologic symptoms. A comparison between CT scan and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kawabata, N.; Tanaka, T.; Hiramoto, N.; Takazuka, K.; Komatsu, T.

    1987-03-01

    The lack of neurologic symptoms is rare in herpes simplex encephalitis (HSE). A 42-year-old woman presented with psychiatric features alone, such as Korsakoff syndrome and abortive type Kluver-Bucy syndrome. The diagnosis of HSE was confirmed by serologically elevated antibody titer. The patient underwent both X-ray computed tomography and magnetic resonance imaging (MRI). X-ray computed tomography showed transient contrast enhancement and low density area confined to the lateral lobe. Magnetic resonance imaging revealed diffuse areas with a high MRI signal intensity. Considering that the lack of neurologic features, as seen in the present HSE patient, may sometimes rule out the possibility of parenchymal disease, imaging modalities, especially MRI, may be of value in the detection of lesions for HSE.

  20. Synergism of herpes simplex virus and tobacco-specific N'-nitrosamines in cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Park, N.H.; Dokko, H.; Li, S.L.; Cherrick, H.M. (UCLA School of Dentistry (USA))

    1991-03-01

    Previous studies indicate that herpes simplex virus (HSV) enhances the carcinogenic activity of smokeless tobacco and tobacco-related chemical carcinogens in animals. Since tobacco-specific N'-nitrosamines (TSNAs) such as N'-nitrosonornicotine (NNN) and 4-(N-methyl-N'-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are major chemical carcinogens of smokeless tobacco and are known to be responsible for the development of oral cancers in smokeless tobacco users, the combined effects of TSNAs and HSV in cell transformation were investigated. Exposure of cells to NNN or NNK followed by virus infection resulted in a significant enhancement of transformation frequency when compared with that observed with chemical carcinogens or virus alone. This study suggests that TSNAs and HSV can interact together and show synergism in cell transformation.

  1. Construction and characterization of bacterial artificial chromosomes (BACs) containing herpes simplex virus full-length genomes.

    Science.gov (United States)

    Nagel, Claus-Henning; Pohlmann, Anja; Sodeik, Beate

    2014-01-01

    Bacterial artificial chromosomes (BACs) are suitable vectors not only to maintain the large genomes of herpesviruses in Escherichia coli but also to enable the traceless introduction of any mutation using modern tools of bacterial genetics. To clone a herpes simplex virus genome, a BAC replication origin is first introduced into the viral genome by homologous recombination in eukaryotic host cells. As part of their nuclear replication cycle, genomes of herpesviruses circularize and these replication intermediates are then used to transform bacteria. After cloning, the integrity of the recombinant viral genomes is confirmed by restriction length polymorphism analysis and sequencing. The BACs may then be used to design virus mutants. Upon transfection into eukaryotic cells new herpesvirus strains harboring the desired mutations can be recovered and used for experiments in cultured cells as well as in animal infection models.

  2. Inhibition of herpes simplex virus multiplication by activated macrophages: a role for arginase?

    Science.gov (United States)

    Wildy, P; Gell, P G; Rhodes, J; Newton, A

    1982-01-01

    Proteose-peptone-activated mouse macrophages can prevent productive infection by herpes simplex virus in neighboring cells in vitro whether or not those cells belong to the same animal species. The effect does not require contact between the macrophages and the infected cells, may be prevented by adding extra arginine to the medium, and may be reversed when extra arginine is added 24 h after the macrophages. Arginase activity was found both intracellularly and released from the macrophages. The extracellular enzyme is quite stable; 64% activity was found after 48 h of incubation at 37 degrees C in tissue culture medium. No evidence was found that the inefficiency of virus replication in macrophages was due to self-starvation by arginase. As might be predicted macrophages can, by the same mechanism, limit productive infection by vaccinia virus. PMID:6286497

  3. In vivo fitness and virulence of a drug-resistant herpes simplex virus 1 mutant.

    Science.gov (United States)

    Pesola, Jean M; Coen, Donald M

    2007-05-01

    Two important issues regarding a virus mutant that is resistant to an antiviral drug are its ability to replicate in animal hosts (in vivo fitness) relative to other genetic variants, including wild type, and its ability to cause disease. These issues have been investigated for a herpes simplex virus 1 mutant that is resistant to thiourea compounds, which inhibit encapsidation of viral DNA. Following corneal inoculation of mice, the mutant virus replicated very similarly to its wild-type parent in the eye, trigeminal ganglion and brain. The mutant virus was as lethal to mice as its wild-type parent following this route of inoculation. Indeed, it exhibited increased virulence. Thus, unlike most drug-resistant virus mutants, this mutant retained in vivo fitness and virulence.

  4. The effect of cyclin-dependent kinases inhibitor treatment on experimental herpes simplex encephalitis mice.

    Science.gov (United States)

    Zhou, Yu; Zeng, Yan-Ping; Zhou, Qin; Guan, Jing-Xia; Lu, Zu-Neng

    2016-08-01

    Herpes simplex encephalitis(HSE) is the most common and serious viral encephalitis in humans. There is a lack of effective medication to date for HSE. A better understanding of the mediators of tissue damage is essential for finding new targets for therapeutic intervention. In this project, we explored the effect of cyclin-dependent kinases inhibitor olomoucine treatment on experimental HSE mice. The following results were obtained: (1) olomoucine increased survival in HSE mice; (2) olomoucine inhibited microglial activation and reduced HSV-1-induced cytokines release; (3) olomoucine prevented neural cells apoptosis and attenuated brain tissue pathological changes following HSV-1 infection; (4) olomoucine reduced brain edema and improved neurological function in HSE. Overall, olomoucine can induce a blunted inflammatory response, maintain the blood vessel wall intact, improve neurological function and increase survival in HSE mice.

  5. Validity of the coding for herpes simplex encephalitis in the Danish National Patient Registry

    DEFF Research Database (Denmark)

    Jørgensen, Laura Krogh; Dalgaard, Lars Skov; Østergaard, Lars Jørgen;

    2016-01-01

    BACKGROUND: Large health care databases are a valuable source of infectious disease epidemiology if diagnoses are valid. The aim of this study was to investigate the accuracy of the recorded diagnosis coding of herpes simplex encephalitis (HSE) in the Danish National Patient Registry (DNPR......). METHODS: The DNPR was used to identify all hospitalized patients, aged ≥15 years, with a first-time diagnosis of HSE according to the International Classification of Diseases, tenth revision (ICD-10), from 2004 to 2014. To validate the coding of HSE, we collected data from the Danish Microbiology Database......, from departments of clinical microbiology, and from patient medical records. Cases were classified as confirmed, probable, or no evidence of HSE. We estimated the positive predictive value (PPV) of the HSE diagnosis coding stratified by diagnosis type, study period, and department type. Furthermore, we...

  6. Kyrieleis plaques associated with Herpes Simplex Virus type 1 acute retinal necrosis

    Directory of Open Access Journals (Sweden)

    Neha Goel

    2016-04-01

    Full Text Available We report the case of a 55-year-old immunocompetent male who presented with features typical of acute retinal necrosis (ARN. Polymerase chain reaction of the aqueous tap was positive for Herpes Simplex Virus (HSV – 1. Following therapy with intravenous Acyclovir, followed by oral Acyclovir and steroids, there was marked improvement in the visual acuity and clinical picture. At one week after initiation of treatment, Kyrieleis plaques were observed in the retinal arteries. They became more prominent despite resolution of the vitritis, retinal necrosis and vasculitis and persisted till six weeks of follow-up, when fluorescein angiography was performed. The appearance of this segmental retinal periarteritis also known as Kyrieleis plaques has not been described in ARN due to HSV-1 earlier.

  7. Herpes Simplex [corrected] Virus Type 2 Shedding From Male Circumcision Wounds in Rakai, Uganda.

    Science.gov (United States)

    Grabowski, Mary K; Kigozi, Godfrey; Gray, Ronald H; Armour, Benjamin; Manucci, Jordyn; Serwadda, David; Redd, Andrew D; Nalugoda, Fred; Patel, Eshan U; Wawer, Maria J; Quinn, Thomas C; Tobian, Aaron A R

    2015-11-15

    A prospective observational study of 176 men coinfected with human immunodeficiency virus and herpes simplex virus type 2 (HSV-2) was conducted to assess whether their sexual partners may be at an increased risk of HSV-2 from male circumcision (MC) wounds. Preoperative and weekly penile lavage samples were tested for penile HSV-2 shedding. Prevalence risk ratios (PRRs) were estimated using Poisson regression. Detectable penile HSV-2 shedding was present in 9.7% of men (17 of 176) before MC, compared with 12.9% (22 of 170) at 1 week (PRR, 1.33; 95% confidence interval [CI], .74-2.38) and 14.8% (23 of 155) at 2 weeks (PRR, 1.50; 95% CI, .86-2.62) after MC. HSV-2 shedding was lower among men with healed MC wounds (adjusted PRR, 0.62; 95% CI, .35-1.08). Men undergoing MC should be counseled on sexual abstinence and condom use.

  8. Herpes simplex virus infection in burned patients: epidemiology of 11 cases.

    Science.gov (United States)

    Bourdarias, B; Perro, G; Cutillas, M; Castede, J C; Lafon, M E; Sanchez, R

    1996-06-01

    Burned patients suffer significant immunosuppression during the first 3 or 4 weeks after hospitalization. Herpes simplex virus (HSV) infections are commonly seen in immunosuppressed patients and may account for considerable morbidity and some mortality. We studied retrospectively 11 patients with severe burn injury who became infected with HSV. We determined the prevalence of viral infection in this group of patients. Serological testing and viral culture was used to diagnose HSV infection. No general complications appeared in these 11 patients in association with HSV but two patients died of multiorgan failure. Locally, areas of active epidermal regeneration were most commonly affected. Acyclovir therapy was not used and the duration of hospitalization was normal in these 11 patients.

  9. An atypical case of herpes simplex virus endotheliitis presented as bullous keratopathy.

    Science.gov (United States)

    Papaioannou, Lamprini; Tsolkas, Georgios; Theodossiadis, Panagiotis; Papathanassiou, Miltiadis

    2013-12-01

    To present an atypical case of herpes simplex virus (HSV) endotheliitis. The authors report the case of a 62-year-old female patient who presented with unilateral diffuse corneal edema with Descemet's membrane folds and bullae, without keratic precipitates, iritis, significant anterior chamber reaction, or intraocular pressure (IOP) elevation. The patient had no documented positive history of ocular surgery and no abnormal findings were present in the fellow eye. Endotheliitis of viral origin was suspected and Goldmann-Witmer coefficient for HSV, cytomegalovirus, and varicela zoster virus was calculated. Goldmann-Witmer coefficient was positive for HSV. Treatment with oral valacyclovir and topical dexamethasone resulted in complete resolution of corneal edema within 1 week. HSV endotheliitis can present with bullous keratopathy as the only clinical manifestation, without typical findings such as keratic precipitates, iritis, and IOP elevation.

  10. The Herpes Simplex Virus Triplex Protein, VP23, Exists as a Molten Globule

    Science.gov (United States)

    Kirkitadze, Marina D.; Barlow, Paul N.; Price, Nicholas C.; Kelly, Sharon M.; Boutell, Christopher J.; Rixon, Frazer J.; McClelland, David A.

    1998-01-01

    Two proteins, VP19C (50,260 Da) and VP23 (34,268 Da), make up the triplexes which connect adjacent hexons and pentons in the herpes simplex virus type 1 capsid. VP23 was expressed in Escherichia coli and purified to homogeneity by Ni-agarose affinity chromatography. In vitro capsid assembly experiments demonstrated that the purified protein was functionally active. Its physical status was examined by differential scanning calorimetry, ultracentrifugation, size exclusion chromatography, circular dichroism, fluorescence spectroscopy, and 8-anilino-1-naphthalene sulfonate binding studies. These studies established that the bacterially expressed VP23 exhibits properties consistent with its being in a partially folded, molten globule state. We propose that the molten globule represents a functionally relevant intermediate which is necessary to allow VP23 to undergo interaction with VP19C in the process of capsid assembly. PMID:9811746

  11. Current Status of Natural Products from Plants as Anti-herpes Simplex Virus 1 Agents

    Institute of Scientific and Technical Information of China (English)

    Yang-fei XIANG; Ying PEI; Yi-fei WANG

    2008-01-01

    Nucleoside analogues have been the mainstay of clinical treatment of herpes simplex virus 1 (HSV-1) infections since their development. However, the emergence of drug resistant strains has underlined the urgency of the discovery of novel anti-HSV-1 drugs. Natural products, which provided many novel drug leads, are known to be an important source of anti-HSV-1 agents. Herein, we present an overview of natural products with anti-HSV-1 activities isolated from a variety of plants reported in recent years. Several different compounds, mainly belonging to the three groups of polysaccharides, polyphenols and terpenes, showed antiviral effects against HSV-1, indicating their potential to be promising anti-HSV-1 agents.

  12. T Cell Receptor Signaling Pathways:New Targets for Herpes Simplex Virus

    Institute of Scientific and Technical Information of China (English)

    You-jia CAO; Ya-peng LI; Ying-chi ZHANG; Cui-zhu ZHANG

    2008-01-01

    Herpes simplex viruses (HSV-1 and HSV-2) cause global morbidity and synergistically correlate with HIV infection.HSV exists life-long in a latent form in sensory neurons with intermittent reactivation,in despite of host immune surveillance.While abundant evidence for HSV interfering with innate immune responses so as to favor the replication and propagation of the virus,several lines of evidence declare that HSV attenuates adaptive immunity by various mechanisms,including but not limited to the ablation of antigen presentation,induction of apoptosis,and interruption of cellular signaling.In this review,we will focus on the perturbative role of HSV in Tcells signaling.

  13. Prevalence of Intrathecal Acyclovir Resistant Virus in Herpes Simplex Encephalitis Patients

    Science.gov (United States)

    Mitterreiter, Johanna G.; Titulaer, Maarten J.; van Nierop, Gijsbert P.; van Kampen, Jeroen J. A.; Aron, Georgina I.; Osterhaus, Albert D. M. E.; Verjans, Georges M. G. M.; Ouwendijk, Werner J. D.

    2016-01-01

    Herpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted thymidine kinase (TK) protein. Here, we determined the prevalence of intrathecal ACVR–associated HSV TK mutations in HSE patients and compared TK genotypes of sequential HSV isolates in paired cerebrospinal fluid (CSF) and blister fluid of mucosal HSV lesions. Clinical samples were obtained from 12 HSE patients, encompassing 4 HSV type 1 (HSV-1) and 8 HSV-2 encephalitis patients. HSV DNA load was determined by real-time PCR and complete HSV TK gene sequences were obtained by nested PCR followed by Sanger sequencing. All HSV-1 HSE patients contained viral TK mutations encompassing 30 unique nucleotide and 13 distinct amino acid mutations. By contrast, a total of 5 unique nucleotide and 4 distinct amino acid changes were detected in 7 of 8 HSV-2 patients. Detected mutations were identified as natural polymorphisms located in non-conserved HSV TK gene regions. ACV therapy did not induce the emergence of ACVR-associated HSV TK mutations in consecutive CSF and mucocutaneous samples of 5 individual patients. Phenotypic susceptibility analysis of these mucocutaneous HSV isolates demonstrated ACV-sensitive virus in 2 HSV-1 HSE patients, whereas in two HSV-2 HSE patients ACVR virus was detected in the absence of known ACVR-associated TK mutations. In conclusion, we did not detect intrathecal ACVR-associated TK mutations in HSV isolates obtained from 12 HSE patients. PMID:27171421

  14. Antimicrobial Activity of Biocompatible Microemulsions Against Aspergillus niger and Herpes Simplex Virus Type 2

    Science.gov (United States)

    Alkhatib, Mayson H; Aly, Magda M; Rahbeni, Rajaa A; Balamash, Khadijah S

    2016-01-01

    Background Microemulsions (MEs), which consist of oil, water, surfactants, and cosurfactants, have recently generated considerable interest as antimicrobial agents. Objectives To determine the antifungal and antiviral activities of three ME formulations (MEa, MEb, and MEc) that differ in their hydrophilicity. Methods The ME formulas were produced by mixing different fractions of Tween 80, Span 20, ethanol, oil, isopropyl myristate, and distilled water. The antifungal activity of the ME formulas against Aspergillus niger, A. flavus, Bacillus, Candida albicans, and C. glabrata were determined by the solid medium diffusion cytotoxicity test against the mitochondria, measuring the minimum inhibitory concentration, dry biomass, and leakage of potassium, and characterizing the cell morphology. The antiviral activities of the ME formulas against the herpes simplex virus type 2 (HSV-2) were determined using the cytopathic effect assay. Results Significant antimicrobial activities were recorded against A. niger and herpes simplex virus type 2 (HSV-2) when treated with MEb that had hydrophobic nanodroplets with an average diameter of 4.7 ± 1.22 nm. A volume of 0.1 mL of MEb (10 mL of potato dextrose broth) inhibited the germination of A. niger cells, reduced their dry biomass, enhanced the leakage of potassium from the cell membranes, affected their mitochondria, and altered the shape of their conidia, in addition to enlarging them. MEb was able to destroy the HSV-2 virus at a 200-fold dilution in Dulbecco’s modified eagle medium. Conclusions The water-in-oil ME with equivalent surfactant-to-oil ratio (MEb) has great potential as an antifungal and antiviral agent.

  15. Prevalence of Intrathecal Acyclovir Resistant Virus in Herpes Simplex Encephalitis Patients.

    Science.gov (United States)

    Mitterreiter, Johanna G; Titulaer, Maarten J; van Nierop, Gijsbert P; van Kampen, Jeroen J A; Aron, Georgina I; Osterhaus, Albert D M E; Verjans, Georges M G M; Ouwendijk, Werner J D

    2016-01-01

    Herpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted thymidine kinase (TK) protein. Here, we determined the prevalence of intrathecal ACVR-associated HSV TK mutations in HSE patients and compared TK genotypes of sequential HSV isolates in paired cerebrospinal fluid (CSF) and blister fluid of mucosal HSV lesions. Clinical samples were obtained from 12 HSE patients, encompassing 4 HSV type 1 (HSV-1) and 8 HSV-2 encephalitis patients. HSV DNA load was determined by real-time PCR and complete HSV TK gene sequences were obtained by nested PCR followed by Sanger sequencing. All HSV-1 HSE patients contained viral TK mutations encompassing 30 unique nucleotide and 13 distinct amino acid mutations. By contrast, a total of 5 unique nucleotide and 4 distinct amino acid changes were detected in 7 of 8 HSV-2 patients. Detected mutations were identified as natural polymorphisms located in non-conserved HSV TK gene regions. ACV therapy did not induce the emergence of ACVR-associated HSV TK mutations in consecutive CSF and mucocutaneous samples of 5 individual patients. Phenotypic susceptibility analysis of these mucocutaneous HSV isolates demonstrated ACV-sensitive virus in 2 HSV-1 HSE patients, whereas in two HSV-2 HSE patients ACVR virus was detected in the absence of known ACVR-associated TK mutations. In conclusion, we did not detect intrathecal ACVR-associated TK mutations in HSV isolates obtained from 12 HSE patients.

  16. Herpes Simplex

    Science.gov (United States)

    ... Boards study tools Online Learning Center Meetings and events Make a difference Career planning Media Relations Toolkit AAD apps Academy meeting Chronic urticaria—for members Chronic urticaria—for public Dermatology World Dialogues in Dermatology JAAD Mohs AUC ...

  17. Psychosis in a 15-Year-Old Female with Herpes Simplex Encephalitis in a Background of Mannose-Binding Lecithin Deficiency

    Directory of Open Access Journals (Sweden)

    Kenneth Asogwa

    2017-01-01

    Full Text Available Historically, psychotic disorder has been associated with viral infection. Herpes simplex infections and Epstein-Barr virus (EBV among other viral infections have been implicated in psychotic disorder. Of note in this case report is psychotic disorder that occurred following reactivation of herpes simplex infection in a background of mannose-binding lecithin (MBL deficiency, childhood EBV infection, and severe psychosocial stress. Herpes simplex encephalitis (HSE remains a significant cause of morbidity and mortality despite advancement in its treatment with intravenous acyclovir. Many studies have reported psychiatric and neurological manifestation of herpes simplex infection following primary or reactivated infection, while others suggest milder clinical course of herpes simplex encephalitis in a background of immunosuppression. Another contributory factor to psychotic disorder in this case is childhood EBV exposure which has been reported to increase the risk of psychosis in adolescence and adulthood. This case report describes a 15-year-old female with MBL deficiency who presented with psychosis caused by reactivated herpes simplex infection and had good clinical recovery. Based on childhood Epstein-Barr virus exposure and psychosis in adolescence (current case, she is at increased risk of psychotic disorder in adulthood, which underscores the importance of long-term monitoring.

  18. Expression of IFN-Inducible Genes with Antiviral Function OAS1 and MX1 in Health and under Conditions of Recurrent Herpes Simplex Infection.

    Science.gov (United States)

    Karaulov, A V; Shulzhenko, A E; Karsonova, A V

    2017-07-01

    We studied the expression of IFN-inducible genes OAS1 and Mx1 in lysates of peripheral blood mononuclear cells from patients suffering from recurrent Herpes simplex infections in comparison with healthy people. To induce the expression of the studied genes, blood mononuclears were incubated with recombinant IFN-α2b in concentrations of 1, 10, and 100 U/ml for 3 h and then the content of the studied transcripts was evaluated. Relative expression of OAS1 and Mx1 in patients with recurrent forms of Herpes simplex both during the acute stage and clinical remission did not differ significantly from that in healthy people after stimulation with IFN-α2b in a concentration of 1 U/ml and in higher concentrations (10 and 100 U/ml). It was concluded that intracellular signal transduction in IFN-α-activated cells in vitro was not disturbed in patients with recurrent forms of Herpes simplex infection. Thus, the reported phenomenon of IFN-signalling distortion by Herpes simplex virus proteins observed in experiments on model cell lines infected with Herpes simplex virus was not confirmed in our experiments on peripheral blood mononuclear cells from patients with Herpes simplex infection.

  19. Most Common Dermatologic Topics Published in Five High-Impact General Medical Journals, 1970–2012: Melanoma, Psoriasis, Herpes Simplex, Herpes Zoster, and Acne

    Science.gov (United States)

    Choi, Young M; Namavar, Aram A; Wu, Jashin J

    2014-01-01

    Context: General practitioners frequently encounter skin diseases and are accustomed to diagnosing the most common dermatologic conditions. Objective: We sought to determine the most common dermatologic topics published in five high-impact general medical journals (New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, British Medical Journal (now The BMJ), and Annals of Internal Medicine). Design: We conducted an independent search of the Thomson Reuters’ Science Citation Index for common dermatologic topics, limited to the period 1970 to 2012. Main Outcome Measure: Total number of publications dealing with each dermatologic topic considered. Results: The five most common dermatologic topics published were melanoma, psoriasis, herpes simplex, herpes zoster, and acne. Melanoma and psoriasis were the top two dermatologic topics published in each journal except for Annals of Internal Medicine. Conclusions: Internists frequently diagnose herpes simplex, herpes zoster, and acne, which are also common dermatologic topics published. Although internists infrequently diagnose melanoma and psoriasis, they are major topics for general medical journals because of their increased community awareness, major advancements in therapeutic research, and their nondermatologic manifestations. PMID:25662523

  20. Most common dermatologic topics published in five high-impact general medical journals, 1970-2012: melanoma, psoriasis, herpes simplex, herpes zoster, and acne.

    Science.gov (United States)

    Choi, Young M; Namavar, Aram A; Wu, Jashin J

    2014-01-01

    General practitioners frequently encounter skin diseases and are accustomed to diagnosing the most common dermatologic conditions. We sought to determine the most common dermatologic topics published in five high-impact general medical journals (New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, British Medical Journal (now The BMJ), and Annals of Internal Medicine). We conducted an independent search of the Thomson Reuters’ Science Citation Index for common dermatologic topics, limited to the period 1970 to 2012. Total number of publications dealing with each dermatologic topic considered. The five most common dermatologic topics published were melanoma, psoriasis, herpes simplex, herpes zoster, and acne. Melanoma and psoriasis were the top two dermatologic topics published in each journal except for Annals of Internal Medicine. Internists frequently diagnose herpes simplex, herpes zoster, and acne, which are also common dermatologic topics published. Although internists infrequently diagnose melanoma and psoriasis, they are major topics for general medical journals because of their increased community awareness, major advancements in therapeutic research, and their nondermatologic manifestations.

  1. Computational sensing of herpes simplex virus using a cost-effective on-chip microscope

    KAUST Repository

    Ray, Aniruddha

    2017-07-03

    Caused by the herpes simplex virus (HSV), herpes is a viral infection that is one of the most widespread diseases worldwide. Here we present a computational sensing technique for specific detection of HSV using both viral immuno-specificity and the physical size range of the viruses. This label-free approach involves a compact and cost-effective holographic on-chip microscope and a surface-functionalized glass substrate prepared to specifically capture the target viruses. To enhance the optical signatures of individual viruses and increase their signal-to-noise ratio, self-assembled polyethylene glycol based nanolenses are rapidly formed around each virus particle captured on the substrate using a portable interface. Holographic shadows of specifically captured viruses that are surrounded by these self-assembled nanolenses are then reconstructed, and the phase image is used for automated quantification of the size of each particle within our large field-of-view, ~30 mm2. The combination of viral immuno-specificity due to surface functionalization and the physical size measurements enabled by holographic imaging is used to sensitively detect and enumerate HSV particles using our compact and cost-effective platform. This computational sensing technique can find numerous uses in global health related applications in resource-limited environments.

  2. Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings From a Randomized Trial.

    Science.gov (United States)

    Bernstein, David I; Wald, Anna; Warren, Terri; Fife, Kenneth; Tyring, Stephen; Lee, Patricia; Van Wagoner, Nick; Magaret, Amalia; Flechtner, Jessica B; Tasker, Sybil; Chan, Jason; Morris, Amy; Hetherington, Seth

    2017-03-15

    Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant. Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose. One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P < .001] and from 15.0% to 10.3% for 100 µg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses. GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates. NCT01667341 (funded by Genocea).

  3. HERPES SIMPLEX VIRUS IN SALIVA OF PATIENTS WITH BELL'S PALSY

    Directory of Open Access Journals (Sweden)

    M.H. Harirchian

    2008-04-01

    Full Text Available Acute idiopathic peripheral facial paralysis (Bell's palsy is the most common disorder of the facial nerve. Most patients recover completely, although some have permanent disfiguring facial weakness. Many studies have attempted to identify an infectious etiology for this disease. Although the cause of Bell's palsy remains unknown, recent studies suggest a possible association with Herpes Simplex Virus-1(HSV-1 infection. In this case-control study we investigated the presence of DNA of HSV in the saliva of 26 patients with Bells palsy in first and second weeks of disorder compared to normal population who were matched in sex, age, as well as history of diabetes mellitus, hypertension and labial herpes. In the case group 3 and 7 patients had positive polymerase chain reaction (PCR for HSV in first and second weeks of disease respectively compared to 4 in controls. It means that there was not any relationship between Bell's palsy and HSV in saliva either in first or in second week. Two and 6 of positive results from the sample of first and second weeks were from patients with severe (grade 4-6 Bell's palsy. Although the positive results were more in second week in patient group and more in severe palsies, but a significant relationship between Bell's palsy or its severity and positive PCR for HSV was not detected (P >0.05.

  4. Preliminary study on Herpes simplex virus type 1 infection of human oral epithelial cell in vitro

    Institute of Scientific and Technical Information of China (English)

    Jie Zhao; Weibin Sun; Juan Wang

    2008-01-01

    Objective: To explore the functions and mechanisms of herpes simplex virus type 1(HSV-1) while infecting human oral epithelial cells in vitro(being similar to the infection in vivo). Methods:An abundance of HSV-1 strains amplified in Vero cells were used to infect human oral epithelial cells. The culture supernatant was collected to infect Veto cells again. Morphology of HSV-1 was identified by inverted microscope and transmission electron microscope. Nucleic acid of the virus was detected by PCR. Results:The infected human oral epithelial cells didn't display an obvious cytopathic effect(CPE) under inverted microscope(while Veto cells which were infected by the culture supematant showed typical(CPE). The virus particles were not observed in the cytoplasm nor in nucleus of human oral epithelial cells, however under transmission electron microscope in the cytoplasm of Vero cells, the nucleic acid of HSV-1 could be detected in infected human oral epithelial cells, by PCR. Conclusion:HSV-1 can successfully infect human oral epithelial cells. This model may provide a useful approach for studying the pathogenesis of herpes virus-associated periodontal disease.

  5. Herpes Simplex Virus Type 1 infection: overview on relevant clinico-pathological features.

    Science.gov (United States)

    Arduino, Paolo G; Porter, Stephen R

    2008-02-01

    Herpes Simplex Virus Type 1 (HSV-1) is a nuclear replicating enveloped virus, usually acquired through direct contact with infected lesions or body fluids (typically saliva). The prevalence of HSV-1 infection increases progressively from childhood, the seroprevalence being inversely related to socioeconomic background. Primary HSV-1 infections in children are either asymptomatic or following an incubation period of about 1 week gives rise to mucocutaneous vesicular eruptions. Herpetic gingivostomatitis typically affects the tongue, lips, gingival, buccal mucosa and the hard and soft palate. Most primary oro-facial HSV infection is caused by HSV-1, infection by HSV-2 is increasingly common. Recurrent infections, which occur at variable intervals, typically give rise to vesiculo-ulcerative lesions at mucocutaneous junctions particularly the lips (herpes labialis). Recurrent HSV-1 infection within the mouth is uncommon in otherwise healthy patients, although in immunocompromised patients, recurrent infection can be more extensive and/or aggressive. The diagnosis of common herpetic infection can usually be based upon the clinical history and presenting features. Confirmatory laboratory diagnosis is, however, required when patients are, or may be, immunocompromised.

  6. Long-Term Isoflurane Therapy for Refractory Bronchospasm Associated with Herpes Simplex Pneumonia in a Heart Transplant Patient

    Directory of Open Access Journals (Sweden)

    C. Hornuss

    2010-01-01

    Full Text Available A 47-year-old man with a history of heart transplant was admitted after severe traumatic brain injury and seizures. During mechanical ventilation, the patient developed bronchospasm that severely compromised respiratory function that led to cardiac arrest. After resuscitation, application of isoflurane through the Anaesthetic Conserving Device (AnaConDa in the ICU successfully treated bronchospasm, provided adequate sedation, and enabled appropriate ventilation and diagnostic bronchoscopy. A subsequent bronchoalveolar lavage revealed a high amount of Herpes simplex DNA. Herpes simplex pneumonia was diagnosed and treated with acyclovir. Isoflurane treatment was applied for twelve days total without side effects on renal and cerebral function. The patient recovered quickly after the termination of sedation. At discharge, he was fully awake without focal neurological deficiency and his long-term outcome was excellent. This case demonstrates that isoflurane is a treatment option in life-threatening cases of bronchospasm and a safe option for long-term sedation.

  7. In vivo gene therapy for pyridoxine-induced neuropathy by herpes simplex virus-mediated gene transfer of neurotrophin-3.

    Science.gov (United States)

    Chattopadhyay, Munmun; Wolfe, Darren; Huang, Shaohua; Goss, James; Glorioso, Joseph C; Mata, Marina; Fink, David J

    2002-01-01

    Neurotrophic factors have been demonstrated to prevent the development of peripheral neuropathy in animal models, but the therapeutic use of these factors in human disease has been limited by the short serum half-life and dose-limiting side effects of these potent peptides. We used peripheral subcutaneous inoculation with a replication-incompetent, genomic herpes simplex virus-based vector containing the coding sequence for neurotrophin-3 to transduce sensory neurons of the rat dorsal root ganglion in vivo, and found that expression of neurotrophin-3 from the vector protected peripheral sensory axons from neuropathy induced by intoxication with pyridoxine assessed by electrophysiological (foot sensory response amplitude, and conduction velocity, and H-wave), histological (nerve morphology and morphometry), and behavioral measures of proprioceptive function. In vivo gene transfer using herpes simplex virus vectors provides a unique option for treatment of diseases of the sensory peripheral nervous system.

  8. Virostatic potential of micro-nano filopodia-like ZnO structures against herpes simplex virus-1

    OpenAIRE

    Mishra, Yogendra Kumar; Adelung, Rainer; Roehl, Claudia; Shukla, Deepak; Spors, Frank; Tiwari, Vaibhav

    2011-01-01

    Herpes simplex virus type-1 (HSV-1) entry into target cell is initiated by the ionic interactions between positively charged viral envelop glycoproteins and a negatively charged cell surface heparan sulfate (HS). This first step involves the induction of HS-rich filopodia-like structures on the cell surface that facilitate viral transport during cell entry. Targeting this initial first step in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro-nano structures (MNSs) that were c...

  9. Successful Treatment of Corticosteroid with Antiviral Therapy for a Neonatal Liver Failure with Disseminated Herpes Simplex Virus Infection

    OpenAIRE

    Shinji Maeba; Shunji Hasegawa; Maiko Shimomura; Takuya Ichimura; Kazumasa Takahashi; Masashi Motoyama; Shinnosuke Fukunaga; Yoshinori Ito; Takashi Ichiyama; Shouichi Ohga

    2015-01-01

    Background - Herpes simplex virus (HSV) infection carries one of the poorest outcomes of neonatal liver failure (NLF). Neonates with disseminated HSV infection can develop hemophagocytic lymphohistiocytosis (HLH), and occasionally need orthotopic liver transplantation. Early interventions may be critical for the cure of NLF. Case Report - We describe herewith a 6-day-old neonate with fulminant hepatic failure due to disseminated HSV-1 infection, who successfully responded to high-dose cor...

  10. Detection and differentiation of herpes simplex viruses by use of the viper platform: advantages, limitations, and concerns.

    Science.gov (United States)

    Lang, Amanda L S; Roberts, Catherine; Mazzulli, Tony; Hatchette, Todd F; LeBlanc, Jason J

    2014-06-01

    The Viper HSV-Q(x) assay was evaluated for the detection of herpes simplex virus 1 (HSV-1) and HSV-2 in specimens from oral, anogenital, and other miscellaneous sites. The HSV-Q(x) assay was found to be highly sensitive and accurate; however, a gray zone may be required for specimens with values falling between 50 and 800 maximum relative fluorescence units.

  11. Expression of herpes simplex virus 1 microRNAs in cell culture models of quiescent and latent infection.

    Science.gov (United States)

    Jurak, Igor; Hackenberg, Michael; Kim, Ju Youn; Pesola, Jean M; Everett, Roger D; Preston, Chris M; Wilson, Angus C; Coen, Donald M

    2014-02-01

    To facilitate studies of herpes simplex virus 1 latency, cell culture models of quiescent or latent infection have been developed. Using deep sequencing, we analyzed the expression of viral microRNAs (miRNAs) in two models employing human fibroblasts and one using rat neurons. In all cases, the expression patterns differed from that in productively infected cells, with the rat neuron pattern most closely resembling that found in latently infected human or mouse ganglia in vivo.

  12. Neuropatia enterica in un modello murino di infezione del sistema nervoso enterico con Herpes simplex virus di tipo 1

    OpenAIRE

    2013-01-01

    Herpes simplex virus type 1 infection of murine enteric nervous system leads to gut neuropathy. The functional gastrointestinal disorders (FGIDs) are a heterogeneous group of chronic conditions characterized by disabling symptoms and decreased patients’ quality of life (Corazziari et al., 2004; Talley et al., 2008). Among these diseases, the Irritable Bowel Syndrome (IBS) is the most relevant for the severe prognosis and the high social and economic burden (Drossman, 2006; Fichna and Stor...

  13. Herpes simplex and human papillomavirus genital infections: controversy over obstetric management.

    Science.gov (United States)

    Osborne, N G; Adelson, M D

    1990-12-01

    Plasma inhibitory factors, high levels of sex hormones, and depression of cell-mediated immunity may interfere with the natural host resistance to viral infections during pregnancy. It is apparent that hormonal, immunologic, and vascular changes in pregnancy may account for increased replication of herpes and for enhanced growth of condylomatous lesions. The challenge is to develop a rational plan of management for pregnant patients with herpes simplex or human papilloma virus infection. There has been a reevaluation of previous recommendations for the management of herpes in pregnancy. Although the consequences of neonatal infection are severe or fatal, the value of routine weekly screening is questionable. This regimen is a poor predictor of neonatal exposure to herpes since only one fourth of women shedding virus at the time of delivery can be identified by routine cultures. The mode of delivery should therefore be based on the presence or absence of lesions at the time of confinement. Cesarean section should be reserved for patients with lesions or with prodromal symptoms of recurrent disease at the time of delivery. Patients with ruptured membranes and active genital lesions should also be delivered by cesarean section. The spectrum of HPV-related diseases in pregnancy is poorly understood. Many questions remain unanswered. It may not be practical to treat very large or extensive genital warts during pregnancy. A cesarean section may be the best choice in these cases. It may be premature to recommend cesarean section for delivery of all pregnant women with symptomatic genital HPV infection. More data are needed. We recommend laser ablation of condylomatous lesions when discovered during pregnancy. Laser vaporization is associated with minimal morbidity when used by experienced surgeons. Trichloroacetic acid is excellent for minimal disease or for treatment of recurrences in pregnancy. Since the immune system seems to play an important role in control of viral

  14. Herpes Simplex Virus Type 2 Encephalitis as a Cause of Ischemic Stroke: Case Report and Systematic Review of the Literature.

    Science.gov (United States)

    Zis, Panagiotis; Stritsou, Panagiota; Angelidakis, Panagiotis; Tavernarakis, Antonios

    2016-02-01

    Our objective is to describe a patient who developed an ischemic stroke as a complication of herpes simplex virus type 2 (HSV-2) encephalitis and to review the literature. A 45-year-old immune-competent Caucasian man presented with a 24-hour history of confusion and fever, and following clinical and laboratory examination was diagnosed with HSV-2 encephalitis. However, the brain magnetic resonance imaging also showed an acute ischemic infarct in the left frontal lobe corresponding to vascular territories of middle cerebral artery branches. Further screening failed to identify any other cause of the stroke. A systematic literature search was conducted in February 2015 using the PubMed database. Six more cases of herpes simplex virus (HSV) central nervous system (CNS) infection that developed a definite ischemic stroke as a complication of the infection were identified. Ischemic stroke, although infrequent, can complicate the evolution of herpes simplex meningitis or encephalitis. Clinicians should include HSV CNS infection as a possible cause of ischemic stroke, especially in young patients with ischemic stroke of unknown etiology. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Acute retinal necrosis results in low vision in a young patient with a history of herpes simplex virus encephalitis.

    Science.gov (United States)

    Shahi, Sanjeet K

    2016-08-31

    Acute retinal necrosis (ARN), secondary to herpes simplex encephalitis, is a rare syndrome that can present in healthy individuals, as well as immuno-compromised patients. Most cases are caused by a secondary infection from the herpes virus family, with varicella zoster virus being the leading cause of this syndrome. Potential symptoms include blurry vision, floaters, ocular pain and photophobia. Ocular findings may consist of severe uveitis, retinal vasculitis, retinal necrosis, papillitis and retinal detachment. Clinical manifestations of this disease may include increased intraocular pressure, optic disc oedema, optic neuropathy and sheathed retinal arterioles. A complete work up is essential to rule out cytomegalovirus retinitis, herpes simplex encephalitis, herpes virus, syphilis, posterior uveitis and other conditions. Depending on the severity of the disease, the treatment options consist of anticoagulation therapy, cycloplegia, intravenous acyclovir, systemic steroids, prophylactic laser photocoagulation and pars plana vitrectomy with silicon oil for retinal detachment. An extensive history and clinical examination is crucial in making the correct diagnosis. Also, it is very important to be aware of low vision needs and refer the patients, if expressing any sort of functional issues with completing daily living skills, especially reading. In this article, we report one case of unilateral ARN 20 years after herpetic encephalitis.

  16. Quantitative Evaluation of Protein Heterogeneity within Herpes Simplex Virus 1 Particles.

    Science.gov (United States)

    El Bilali, Nabil; Duron, Johanne; Gingras, Diane; Lippé, Roger

    2017-05-15

    Several virulence genes have been identified thus far in the herpes simplex virus 1 genome. It is also generally accepted that protein heterogeneity among virions further impacts viral fitness. However, linking this variability directly with infectivity has been challenging at the individual viral particle level. To address this issue, we resorted to flow cytometry (flow virometry), a powerful approach we recently employed to analyze individual viral particles, to identify which tegument proteins vary and directly address if such variability is biologically relevant. We found that the stoichiometry of the UL37, ICP0, and VP11/12 tegument proteins in virions is more stable than the VP16 and VP22 tegument proteins, which varied significantly among viral particles. Most interestingly, viruses sorted for their high VP16 or VP22 content yielded modest but reproducible increases in infectivity compared to their corresponding counterparts containing low VP16 or VP22 content. These findings were corroborated for VP16 in short interfering RNA experiments but proved intriguingly more complex for VP22. An analysis by quantitative Western blotting revealed substantial alterations of virion composition upon manipulation of individual tegument proteins and suggests that VP22 protein levels acted indirectly on viral fitness. These findings reaffirm the interdependence of the virion components and corroborate that viral fitness is influenced not only by the genome of viruses but also by the stoichiometry of proteins within each virion.IMPORTANCE The ability of viruses to spread in animals has been mapped to several viral genes, but other factors are clearly involved, including virion heterogeneity. To directly probe whether the latter influences viral fitness, we analyzed the protein content of individual herpes simplex virus 1 particles using an innovative flow cytometry approach. The data confirm that some viral proteins are incorporated in more controlled amounts, while others

  17. Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring

    Science.gov (United States)

    Mahic, Milada; Mjaaland, Siri; Bøvelstad, Hege Marie; Gunnes, Nina; Susser, Ezra; Bresnahan, Michaeline; Øyen, Anne-Siri; Levin, Bruce; Che, Xiaoyu; Hirtz, Deborah; Reichborn-Kjennerud, Ted; Schjølberg, Synnve; Roth, Christine; Magnus, Per; Stoltenberg, Camilla; Surén, Pål; Hornig, Mady

    2017-01-01

    ABSTRACT Maternal infections during pregnancy are associated with risk of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Proposed pathogenetic mechanisms include fetal infection, placental inflammation, and maternal cytokines or antibodies that cross the placenta. The Autism Birth Cohort comprises mothers, fathers, and offspring recruited in Norway in 1999 to 2008. Through questionnaire screening, referrals, and linkages to a national patient registry, 442 mothers of children with ASD were identified, and 464 frequency-matched controls were selected. Immunoglobulin G (IgG) antibodies to Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and HSV-2 in plasma collected at midpregnancy and after delivery were measured by multiplexed immunoassays. High levels of HSV-2 IgG antibodies in maternal midpregnancy plasma were associated with increased risk of ASD in male offspring (an increase in HSV-2 IgG levels from 240 to 640 arbitrary units/ml was associated with an odds ratio of 2.07; 95% confidence interval, 1.06 to 4.06; P = 0.03) when adjusted for parity and child’s birth year. No association was found between ASD and the presence of IgG antibodies to Toxoplasma gondii, rubella virus, CMV, or HSV-1. Additional studies are needed to test for replicability of risk and specificity of the sex effect and to examine risk associated with other infections. IMPORTANCE The cause (or causes) of most cases of autism spectrum disorder is unknown. Evidence from epidemiological studies and work in animal models of neurodevelopmental disorders suggest that both genetic and environmental factors may be implicated. The latter include gestational infection and immune activation. In our cohort, high levels of antibodies to herpes simplex virus 2 at midpregnancy were associated with an elevated risk of autism spectrum disorder in male offspring. These findings provide support for the hypothesis that gestational infection

  18. Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring.

    Science.gov (United States)

    Mahic, Milada; Mjaaland, Siri; Bøvelstad, Hege Marie; Gunnes, Nina; Susser, Ezra; Bresnahan, Michaeline; Øyen, Anne-Siri; Levin, Bruce; Che, Xiaoyu; Hirtz, Deborah; Reichborn-Kjennerud, Ted; Schjølberg, Synnve; Roth, Christine; Magnus, Per; Stoltenberg, Camilla; Surén, Pål; Hornig, Mady; Lipkin, W Ian

    2017-01-01

    Maternal infections during pregnancy are associated with risk of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Proposed pathogenetic mechanisms include fetal infection, placental inflammation, and maternal cytokines or antibodies that cross the placenta. The Autism Birth Cohort comprises mothers, fathers, and offspring recruited in Norway in 1999 to 2008. Through questionnaire screening, referrals, and linkages to a national patient registry, 442 mothers of children with ASD were identified, and 464 frequency-matched controls were selected. Immunoglobulin G (IgG) antibodies to Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and HSV-2 in plasma collected at midpregnancy and after delivery were measured by multiplexed immunoassays. High levels of HSV-2 IgG antibodies in maternal midpregnancy plasma were associated with increased risk of ASD in male offspring (an increase in HSV-2 IgG levels from 240 to 640 arbitrary units/ml was associated with an odds ratio of 2.07; 95% confidence interval, 1.06 to 4.06; P = 0.03) when adjusted for parity and child's birth year. No association was found between ASD and the presence of IgG antibodies to Toxoplasma gondii, rubella virus, CMV, or HSV-1. Additional studies are needed to test for replicability of risk and specificity of the sex effect and to examine risk associated with other infections. IMPORTANCE The cause (or causes) of most cases of autism spectrum disorder is unknown. Evidence from epidemiological studies and work in animal models of neurodevelopmental disorders suggest that both genetic and environmental factors may be implicated. The latter include gestational infection and immune activation. In our cohort, high levels of antibodies to herpes simplex virus 2 at midpregnancy were associated with an elevated risk of autism spectrum disorder in male offspring. These findings provide support for the hypothesis that gestational infection may

  19. Disseminated cutaneous Herpes Simplex Virus-1 in a woman with rheumatoid arthritis receiving Infliximab: A case report

    Directory of Open Access Journals (Sweden)

    Justice Elizabeth

    2008-08-01

    Full Text Available Abstract Introduction We present the case of a 49-year-old woman with a seronegative rheumatoid arthritis who developed pustular psoriasis whilst on etanercept and subsequently developed disseminated herpes simplex on infliximab. Case presentation Our patient presented with an inflammatory arthritis which failed to respond to both methotrexate and leflunomide, and sulphasalazine treatment led to side effects. She was started on etanercept but after 8 months of treatment developed scaly pustular lesions on her palms and soles typical of pustular psoriasis. Following the discontinuation of etanercept, our patient required high doses of oral prednisolone to control her inflammatory arthritis. A second biologic agent, infliximab, was introduced in addition to low-dose methotrexate and 15 mg of oral prednisolone. However, after just 3 infusions of infliximab, she was admitted to hospital with a fever, widespread itchy vesicular rash and worsening inflammatory arthritis. Fluid from skin vesicles examined by polymerase chain reaction showed Herpes Simplex Virus type 1. Blood cultures were negative and her chest X-ray was normal. Her infliximab was discontinued and she was started on acyclovir, 800 mg five times daily for 2 weeks. She made a good recovery with improvement in her skin within 48 hours. She continued for 2 months on a prophylactic dose of 400 mg bd. Her rheumatoid arthritis became increasingly active and a decision was made to introduce adalimumab alongside acyclovir. Acyclovir prophylaxis has been continued but the dose tapered so that she is taking only 200 mg of acyclovir on alternate days. There has been no recurrence of Herpes Simplex Virus lesions despite increasing adalimumab to 40 mg weekly 3 months after starting treatment. Conclusion We believe this to be the first reported case of widespread cutaneous Herpes Simplex Virus type 1 infection following treatment with infliximab. We discuss the clinical manifestations of Herpes

  20. The herpes simplex virus 2 UL21 protein is essential for virus propagation.

    Science.gov (United States)

    Le Sage, Valerie; Jung, Masany; Alter, Jake D; Wills, Elizabeth G; Johnston, Susan M; Kawaguchi, Yasushi; Baines, Joel D; Banfield, Bruce W

    2013-05-01

    Herpes simplex virus 2 (HSV-2) is an important human pathogen that is the major cause of genital herpes infections and a significant contributor to the epidemic spread of human immunodeficiency virus infections. The UL21 gene is conserved throughout the Alphaherpesvirinae subfamily and encodes a tegument protein that is dispensable for HSV-1 and pseudorabies virus replication in cultured cells; however, its precise functions have not been determined. To investigate the role of UL21 in the HSV-2 replicative cycle, we constructed a UL21 deletion virus (HSV-2 ΔUL21) using an HSV-2 bacterial artificial chromosome, pYEbac373. HSV-2 ΔUL21 was unable to direct the production of infectious virus in noncomplementing cells, whereas the repaired HSV-2 ΔUL21 strain grew to wild-type (WT) titers, indicating that UL21 is essential for virus propagation. Cells infected with HSV-2 ΔUL21 demonstrated a 2-h delay in the kinetics of immediate early viral gene expression. However, this delay in gene expression was not responsible for the inability of cells infected with HSV-2 ΔUL21 to produce virus insofar as late viral gene products accumulated to WT levels by 24 h postinfection (hpi). Electron and fluorescence microscopy studies indicated that DNA-containing capsids formed in the nuclei of ΔUL21-infected cells, while significantly reduced numbers of capsids were located in the cytoplasm late in infection. Taken together, these data indicate that HSV-2 UL21 has an early function that facilitates viral gene expression as well as a late essential function that promotes the egress of capsids from the nucleus.

  1. Mechanism of herpes simplex virus type 2 suppression by propolis extracts.

    Science.gov (United States)

    Nolkemper, Silke; Reichling, Jürgen; Sensch, Karl Heinz; Schnitzler, Paul

    2010-02-01

    Genital herpes caused by herpes simplex virus type 2 (HSV-2) is a chronic, persistent infection spreading efficiently and silently as sexually transmitted disease through the population. Antiviral agents currently applied for the treatment of herpesvirus infections include acyclovir and derivatives. Aqueous and ethanolic extracts of propolis were phytochemically analysed, different polyphenols, flavonoids and phenylcarboxylic acids were identified as major constituents. The aqueous propolis extract revealed a relatively high amount of phenylcarboxylic acids and low concentrations flavonoids when compared to the ethanolic special extract GH 2002. The cytotoxic and antiherpetic effect of propolis extracts against HSV-2 was analysed in cell culture, and revealed a moderate cytotoxicity on RC-37 cells. The 50% inhibitory concentration (IC(50)) of aqueous and ethanolic GH 2002 propolis extracts for HSV-2 plaque formation was determined at 0.0005% and 0.0004%, respectively. Both propolis extracts exhibited high levels of antiviral activity against HSV-2 in viral suspension tests, infectivity was significantly reduced by >99% and a direct concentration- and time-dependent antiherpetic activity could be demonstrated for both extracts. In order to determine the mode of virus suppression by propolis, the extracts were added at different times during the viral infection cycle. Addition of these drugs to uninfected cells prior to infection or to herpesvirus-infected cells during intracellular replication had no effect on virus multiplication. However both propolis extracts exhibited high anti-herpetic activity when viruses were pretreated with these drugs prior to infection. Selectivity indices were determined at 80 and 42.5 for the aqueous and ethanolic extract, respectively, thus propolis extracts might be suitable for topical therapy in recurrent herpetic infection.

  2. Herpes simplex virus induces neural oxidative damage via microglial cell Toll-like receptor-2

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    Little Morgan R

    2010-06-01

    Full Text Available Abstract Background Using a murine model of herpes simplex virus (HSV-1 encephalitis, our laboratory has determined that induction of proinflammatory mediators in response to viral infection is largely mediated through a Toll-like receptor-2 (TLR2-dependent mechanism. Published studies have shown that, like other inflammatory mediators, reactive oxygen species (ROS are generated during viral brain infection. It is increasingly clear that ROS are responsible for facilitating secondary tissue damage during central nervous system infection and may contribute to neurotoxicity associated with herpes encephalitis. Methods Purified microglial cell and mixed neural cell cultures were prepared from C57B/6 and TLR2-/- mice. Intracellular ROS production in cultured murine microglia was measured via 2', 7'-Dichlorofluorescin diacetate (DCFH-DA oxidation. An assay for 8-isoprostane, a marker of lipid peroxidation, was utilized to measure free radical-associated cellular damage. Mixed neural cultures obtained from β-actin promoter-luciferase transgenic mice were used to detect neurotoxicity induced by HSV-infected microglia. Results Stimulation with HSV-1 elevated intracellular ROS in wild-type microglial cell cultures, while TLR2-/- microglia displayed delayed and attenuated ROS production following viral infection. HSV-infected TLR2-/- microglia produced less neuronal oxidative damage to mixed neural cell cultures in comparison to HSV-infected wild-type microglia. Further, HSV-infected TLR2-/- microglia were found to be less cytotoxic to cultured neurons compared to HSV-infected wild-type microglia. These effects were associated with decreased activation of p38 MAPK and p42/p44 ERK in TLR2-/- mice. Conclusions These studies demonstrate the importance of microglial cell TLR2 in inducing oxidative stress and neuronal damage in response to viral infection.

  3. Cryo electron tomography of herpes simplex virus during axonal transport and secondary envelopment in primary neurons.

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    Iosune Ibiricu

    2011-12-01

    Full Text Available During herpes simplex virus 1 (HSV1 egress in neurons, viral particles travel from the neuronal cell body along the axon towards the synapse. Whether HSV1 particles are transported as enveloped virions as proposed by the 'married' model or as non-enveloped capsids suggested by the 'separate' model is controversial. Specific viral proteins may form a recruitment platform for microtubule motors that catalyze such transport. However, their subviral location has remained elusive. Here we established a system to analyze herpesvirus egress by cryo electron tomography. At 16 h post infection, we observed intra-axonal transport of progeny HSV1 viral particles in dissociated hippocampal neurons by live-cell fluorescence microscopy. Cryo electron tomography of frozen-hydrated neurons revealed that most egressing capsids were transported independently of the viral envelope. Unexpectedly, we found not only DNA-containing capsids (cytosolic C-capsids, but also capsids lacking DNA (cytosolic A-/B-capsids in mid-axon regions. Subvolume averaging revealed lower amounts of tegument on cytosolic A-/B-capsids than on C-capsids. Nevertheless, all capsid types underwent active axonal transport. Therefore, even few tegument proteins on the capsid vertices seemed to suffice for transport. Secondary envelopment of capsids was observed at axon terminals. On their luminal face, the enveloping vesicles were studded with typical glycoprotein-like spikes. Furthermore, we noted an accretion of tegument density at the concave cytosolic face of the vesicle membrane in close proximity to the capsids. Three-dimensional analysis revealed that these assembly sites lacked cytoskeletal elements, but that filamentous actin surrounded them and formed an assembly compartment. Our data support the 'separate model' for HSV1 egress, i.e. progeny herpes viruses being transported along axons as subassemblies and not as complete virions within transport vesicles.

  4. A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

    Science.gov (United States)

    Kennedy, Peter G. E.; Rovnak, Joel; Badani, Hussain

    2015-01-01

    Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephalitis; however, a third of the cases of HSV-1 encephalitis are associated with HSV-1 primary infection. Primary VZV infection causes varicella (chickenpox) following which latent virus may reactivate decades later to produce herpes zoster (shingles), as well as an increasingly recognized number of subacute, acute and chronic neurological conditions. Following primary infection, both viruses establish a latent infection in neuronal cells in human peripheral ganglia. However, the detailed mechanisms of viral latency and reactivation have yet to be unravelled. In both cases latent viral DNA exists in an ‘end-less’ state where the ends of the virus genome are joined to form structures consistent with unit length episomes and concatemers, from which viral gene transcription is restricted. In latently infected ganglia, the most abundantly detected HSV-1 RNAs are the spliced products originating from the primary latency associated transcript (LAT). This primary LAT is an 8.3 kb unstable transcript from which two stable (1.5 and 2.0 kb) introns are spliced. Transcripts mapping to 12 VZV genes have been detected in human ganglia removed at autopsy; however, it is difficult to ascribe these as transcripts present during latent infection as early-stage virus reactivation may have transpired in the post-mortem time period in the ganglia. Nonetheless, low-level transcription of VZV ORF63 has been repeatedly detected in multiple ganglia removed as close to death as possible. There is

  5. The role of topical 5% acyclovir and 1% hydrocortisone cream (Xerese™) in the treatment of recurrent herpes simplex labialis.

    Science.gov (United States)

    Hull, Christopher M; Brunton, Stephen

    2010-09-01

    Recurrent herpes simplex labialis (HSL), also known as orofacial herpes or cold sores, is a common clinical presentation of herpes simplex virus (HSV) infection. It may manifest as painful, distressing, and cosmetically displeasing vesicles on the lips, nose, and nasal septum. Although oral or topical treatment with antiviral agents can reduce the replication of HSV-1, the primary benefits of antiviral therapies for recurrent HSL have been limited to modest reductions in healing time; they do not mitigate the accompanying immune-mediated response of the host to the virus. The addition of a topical corticosteroid to an antiviral cream has been hypothesized to improve the clinical outcome of HSL by decreasing the HSV-related immune-mediated inflammatory skin reaction. A recently developed topical cream containing 5% acyclovir and 1% hydrocortisone (AHC) in a novel cream vehicle has been shown to be safe and effective for the early treatment of recurrent HSL in immunocompetent adult and adolescent patients. In a well-controlled clinical trial, AHC cream significantly reduced the frequency of both ulcerative and nonulcerative recurrences (ie, the prevention of vesicular HSL lesions). Treatment was well tolerated, and there was no evidence of emergence of viral resistance to acyclovir with the addition of hydrocortisone. The AHC cream significantly reduced the recurrence of ulcerative and nonulcerative HSL lesions and shortened healing time with early treatment compared with acyclovir 5% cream and vehicle (placebo) cream. Herpes simplex labialis may not typically be considered a serious medical condition; however, the importance of treating HSL should not be overlooked, considering the continuous increase of the viral pool in the general population and the potential psychological and social consequences of the condition when left untreated.

  6. Interaction of humic acids and humic-acid-like polymers with herpes simplex virus type 1

    Science.gov (United States)

    Klöcking, Renate; Helbig, Björn

    The study was performed in order to compare the antiviral activity against herpes simplex virus type 1 (HSV-1) of synthetic humic-acid-like polymers to that of their low-molecular-weight basic compounds and naturally occurring humic acids (HA) in vitro. HA from peat water showed a moderate antiviral activity at a minimum effective concentration (MEC) of 20 µg/ml. HA-like polymers, i.e. the oxidation products of caffeic acid (KOP), hydrocaffeic acid (HYKOP), chlorogenic acid (CHOP), 3,4-dihydroxyphenylacetic acid (3,4-DHPOP), nordihydroguaretic acid (NOROP), gentisinic acid (GENOP), pyrogallol (PYROP) and gallic acid (GALOP), generally inhibit virus multiplication, although with different potency and selectivity. Of the substances tested, GENOP, KOP, 3,4-DHPOP and HYKOP with MEC values in the range of 2 to 10 µg/ml, proved to be the most potent HSV-1 inhibitors. Despite its lower antiviral potency (MEC 40 µg/ml), CHOP has a remarkable selectivity due to the high concentration of this polymer that is tolerated by the host cells (>640 µg/ml). As a rule, the antiviral activity of the synthetic compounds was restricted to the polymers and was not preformed in the low-molecular-weight basic compounds. This finding speaks in favour of the formation of antivirally active structures during the oxidative polymerization of phenolic compounds and, indirectly, of corresponding structural parts in different HA-type substances.

  7. Herpes simplex virus type 1 (HSV-1)-derived recombinant vectors for gene transfer and gene therapy.

    Science.gov (United States)

    Marconi, Peggy; Fraefel, Cornel; Epstein, Alberto L

    2015-01-01

    Herpes simplex virus type 1 (HSV-1 ) is a human pathogen whose lifestyle is based on a long-term dual interaction with the infected host, being able to establish both lytic and latent infections. The virus genome is a 153-kilobase pair (kbp) double-stranded DNA molecule encoding more than 80 genes. The interest of HSV-1 as gene transfer vector stems from its ability to infect many different cell types, both quiescent and proliferating cells, the very high packaging capacity of the virus capsid, the outstanding neurotropic adaptations that this virus has evolved, and the fact that it never integrates into the cellular chromosomes, thus avoiding the risk of insertional mutagenesis. Two types of vectors can be derived from HSV-1, recombinant vectors and amplicon vectors, and different methodologies have been developed to prepare large stocks of each type of vector. This chapter summarizes the approach most commonly used to prepare recombinant HSV-1 vectors through homologous recombination, either in eukaryotic cells or in bacteria.

  8. Antiviral activity of monoterpenes beta-pinene and limonene against herpes simplex virus in vitro.

    Directory of Open Access Journals (Sweden)

    Akram Astani

    2014-06-01

    Full Text Available Essential oils are complex mixtures containing compounds of several different functional- group classes. Depending on the structure, we can distinguish monoterpenes, phenylpropanes, and other components. Here in this study two monoterpene compounds of essential oils, i.e. β-pinene and limonene were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1 in vitro.All antiviral assays were performed using RC-37 cells. Cytotoxicity was determined in a neutral red assay, antiviral assays were performed with HSV-1 strain KOS. The mode of antiviral action was evaluated at different periods during the viral replication cycle. Acyclovir was used as positive antiviral control.Beta-pinenene and limonenen reduced viral infectivity by 100 %. The mode of antiviral action has been determined, only moderate antiviral effects were revealed by monoterpenes when these drugs were added to host cells prior infection or after entry of HSV into cells. However, both monoterpenes exhibited high anti-HSV-1 activity by direct interaction with free virus particles. Both tested drugs interacted with HSV-1 in a dose-dependent manner thereby inactivating viral infection.These results suggest that monoterpenes in essential oils exhibit antiherpetic activity in the early phase of viral multiplication and might be used as potential antiviral agents.

  9. Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication.

    Science.gov (United States)

    Gu, Haidong

    2016-02-12

    Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced "conquer and compromise" strategy to deal with the host anti-viral defenses. One of HSV-1 α (immediate early) gene products, infected cell protein 0 (ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host.

  10. Functional analysis of transcriptional regulation of herpes simplex virus type 1 tegument protein VP22

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The herpes simplex virus type 1 (HSV-1) tegument proteins have important functions in the viral repli- cation process. In order to investigate the role of the HSV-1 tegument protein VP22 in viral replication, its transcriptional regulation of viral promoters was investigated using the chloramphenicol acetyl- transferase (CAT) assay. The results indicate that VP22 exerts a dose-dependent transcriptional in- hibitory effect on the HSV-1 α4, TK, and gC gene promoters. VP22 had the capacity to repress tran- scriptional activation of promoters via different viral transcription regulatory factors such as VP16 and ICP0, as evidenced by the specific repression of the TK and gC gene promoters by ICP0. In addition, VP22 was capable of inhibiting the promotion of ICP0 transcriptional activation in the presence of HAT PCAF, which is even more remarkable than the VP22 repression of ICP0 transcriptional activation. Fi- nally, the transcriptional inhibitory effect of VP22 on other viral promoters was demonstrated by the analysis of β-galactosidase activities in internal controls.

  11. Herpes Simplex Viral Encephalitis Masquerading as a Classic Left MCA Stroke

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    Peter A. Abdelmalik

    2015-01-01

    Full Text Available Objective. Stroke is a clinical diagnosis, with a history and physical examination significant for acute onset focal neurological symptoms and signs, often occurring in patients with known vascular risk factors and is frequently confirmed radiographically. Case Report. A 79-year-old right-handed woman, with a past medical history of hypertension, hyperlipidemia, and prior transient ischemic attack (TIA, presented with acute onset global aphasia and right hemiparesis, in the absence of fever or prodrome. This was initially diagnosed as a proximal left middle cerebral artery (MCA stroke. However, CT perfusion failed to show evidence of reduced blood volume, and CT angiogram did not show evidence of a proximal vessel occlusion. Furthermore, MRI brain did not demonstrate any areas of restricted diffusion. EEG demonstrated left temporal periodic lateralized epileptiform discharges (PLEDs. The patient was empirically loaded with a bolus valproic acid and started on acyclovir, both intravenously. CSF examination demonstrated a pleocytosis and PCR confirmed the diagnosis of herpes simplex viral encephalitis (HSVE. Conclusions. HSVE classically presents in a nonspecific fashion with fever, headache, and altered mental status. However, acute focal neurological signs, mimicking stroke, are possible. A high degree of suspicion is required to institute appropriate therapy and decrease morbidity and mortality associated with HSVE.

  12. Multi-antigenic DNA immunization using herpes simplex virus type 2 genomic fragments.

    Science.gov (United States)

    Braun, Ralph P; Dong, Lichun; Jerome, Sarah; Herber, Renee; Roberts, Lee K; Payne, Lendon G

    2008-01-01

    A novel DNA vaccine was generated using genomic fragments of a pathogen as the source of both the antigen coding and regulatory regions. The constructs, termed subgenomic vaccines (SGVs), incorporated genomic DNA sequences up to 45 kbp that encompass 15-20 different genes. The SGVs were developed to generate vaccines capable of expressing multiple genes from a single construct, which could be of great benefit for commercialization. The unique feature of the SGVs is that genes are expressed from their native promoters rather than heterologous promoters typical of DNA vaccines. SGVs composed of genomic fragments from the DS-DNA virus Herpes Simplex Virus Type 2 (HSV-2) induced HSV-2 specific immune responses following particle-mediated epidermal delivery (PMED) in mice and these responses protected animals from lethal infectious challenge. A second generation SGV (SGV-H2), intended as an HSV-2 therapeutic vaccine, was generated that had five HSV-2 genes and was capable of generating multi-antigenic responses in naïve mice, and enhancing responses in infected animals. When compared with standard single plasmid vaccines, immunization with the SGV-H2 was found to be at least as effective as single plasmids or plasmid mixtures. The activity of the SGV-H2 could be greatly enhanced by co-delivering plasmids expressing E. coli heat labile toxin (LT) or cholera toxin CT as adjuvants as has been found previously for standard single-gene DNA vaccines.

  13. [The relationship between herpes simplex virus II, human papillomavirus infection and infertility after artificial abortion].

    Science.gov (United States)

    Li, D; Huang, T; Zhang, Z

    1998-06-01

    In order to study the relationship between infection of sexually transmitted virus Herpes simplex virus II (HSV2), Human papillomavirus (HPV) and female infertility after artificial abortion, we collected 60 genital samples from infertile women who had accepted artificial abortions and 39 genital samples from normal women. Polymerase chain reaction (PCR) was used to detect HSV2 and HPV. The results were compared by x2. The positive rate of HSV2 in infertile and normal women were 80.0% and 25.6% respectively, there was a significant difference (P 0.05). Mixed infection rates of HSV2 and HPV were 43.3% and 23.1% in infertile and normal women, a significant difference (P < 0.05) was statistically calculated. The results showed that there was a relationship between infertility after artificial abortion and genital infection of HSV2 and HPV or mited infection of HSV 2 and HPV. Taking total 99 genital samples into calculation, the mired infection rate of HSV 2 was 35.35%, a significant relatedness of HSV2 and HPV infection to infertility was proved by chi 2, chi 2 = 12.5, P < 0.01.

  14. PrP(c) expression influences the establishment of herpes simplex virus type 1 latency.

    Science.gov (United States)

    Thackray, Alana M; Bujdoso, Raymond

    2002-03-01

    PrP(c) is a glycophosphatidylinositol-linked cell-surface protein expressed principally by neural tissue. The normal function of this protein is unestablished, although a role in either transmembrane signaling, cell-cell adhesion, or copper metabolism has been proposed. In this study we have investigated the effect of the neurotropic virus herpes simplex virus type 1 (HSV-1) in strains of mice which express different levels of PrP(c). Viral gene expression under the control of the HSV-1 early promoter IE110, detected either by in situ hybridization for RNA transcripts or by beta-galactosidase (beta-Gal) activity from an inserted lacZ gene, showed that the magnitude of HSV replication was retarded in PrP-/- mice. This was reflected in the lower level of acute viral titers in tissues from these virus-inoculated mice. However, HSV-inoculated PrP-/- mice contained higher levels of latent virus in both peripheral and central nervous tissue than those seen in mice which express PrP(c). Our observations show that lack of PrP(c) expression favors the establishment of HSV latency whereas HSV replication proceeds more efficiently in neuronal tissue that expresses this protein. The data further suggest that PrP(c) may be involved in a metabolic pathway that culminates in apoptosis of neurons that have been infected by neurotropic viruses.

  15. Inhibitory effect of herpes simplex virus type 1 on type 2 virus replication.

    Science.gov (United States)

    Zelená, D; Roubal, J; Vonka, V

    1976-11-01

    Simultaneous infection with herpes simplex type I and type 2 viruses of chick embryo fibroblasts (CEF), which are only permissive for type 2 virus, or rabbit embryo fibroblasts (REF), which are permissive for both virus types, resulted in a marked reduction of type 2 virus production. This effect was dependent on the m.o.i. of type I, being expressed at a high rather than a low m.o.i. The rate of interference decreased with the prolongation of the interval between infection with type 2 and type I viruses. No evidence suggestive of interferon involvement was obtained. Partial inactivation of type 2 virus by ultraviolet irradiation enhanced the inhibitory effect of type I virus. On the other hand, u.v. irradiation of type I virus resulted in a progressive loss of inhibitory activity. The results of the present experiments suggest that a type I genome function is responsible for the interfering effect, and that an early step in the growth of type 2 virus is sensitive to the particular type I virus product involved.

  16. Herpes simplex virus ICP27 increases translation of a subset of viral late mRNAs.

    Science.gov (United States)

    Fontaine-Rodriguez, Errin C; Knipe, David M

    2008-04-01

    The herpes simplex virus (HSV) ICP27 immediate-early protein plays an essential role in the expression of viral late genes. ICP27 is a multifunctional protein and has been reported to regulate multiple steps of mRNA synthesis and processing, including transcription, splicing, and nuclear export. Recently, ICP27 was reported to interact with translation factors and to stimulate translation of the viral late mRNA encoding VP16. We examined the effects of ICP27 on accumulation, nuclear export, and translation of HSV 1 (HSV-1) late mRNAs encoding VP16, ICP5, and gD. We confirm here that ICP27 stimulates translation of VP16 mRNA as well as an additional HSV-1 late ICP5 mRNA. The data presented here demonstrate that translation levels of both VP16 and ICP5 mRNA is reduced during infections with the ICP27-null virus mutant d27-1, and with ICP27 C-terminal deletion mutant viruses n406 and n504, compared to wild-type virus. In contrast, the translation of gD mRNA is not affected by the presence of ICP27 during infection. These data demonstrate that ICP27 functions to increase the translation levels of a subset of HSV-1 late genes, and this function requires the C terminus of ICP27.

  17. Antiviral activity of some Tunisian medicinal plants against Herpes simplex virus type 1.

    Science.gov (United States)

    Sassi, A Ben; Harzallah-Skhiri, F; Bourgougnon, N; Aouni, M

    2008-01-10

    Fifteen species of Tunisian traditional medicinal plants, belonging to 10 families, were selected for this study. They were Inula viscosa (L.) Ait and Reichardia tingitana (L.) Roth ssp. discolor (Pom.) Batt. (Asteraceae), Mesembryanthemum cristallinum L. and M. nodiflorum L. (Aizoaceae), Arthrocnemum indicum (Willd.) Moq., Atriplex inflata Muell., A. parvifolia Lowe var. ifiniensis (Caball) Maire, and Salicornia fruticosa L. (Chenopodiaceae), Cistus monspeliensis L. (Cistaceae), Juniperus phoenicea L. (Cupressaceae), Erica multiflora L. (Ericaceae), Frankenia pulverulenta L. (Frankeniaceae), Hypericum crispum L. (Hypericaceae), Plantago coronopus L. ssp. eu-coronopus Pilger var. vulgaris G.G. (Plantaginaceae) and Zygophyllum album L. (Zygophyllaceae). Fifty extracts prepared from those plants were screened in order to assay their antiviral activity against Herpes simplex virus type 1 (HSV-1), using neutral red incorporation. Extracts from eight plants among these 15 showed some degree of antiviral activity, while the methanolic extract of E. multiflora was highly active with EC(50) of 132.6 microg mL(-1). These results corroborate that medicinal plants from Tunisia can be a rich source of potential antiviral compounds.

  18. Phase-Transitions in a model for the formation of herpes simplex ulcers

    CERN Document Server

    Ferreira, C P; Zorenos dos Santos, R M; Ferreira, Claudia Pio; Fontanari, Jose Fernando; Santos, Rita M. Zorzenon dos

    2001-01-01

    The critical properties of a cellular automaton model describing the spreading of infection of the Herpes Simplex Virus in corneal tissue are investigated through the dynamic Monte Carlo method. The model takes into account different cell susceptibilities to the viral infection, as suggested by experimental findings. In a two-dimensional square lattice, the sites are associated to two distinct types of cells, namely, permissive and resistant to the infection. While a permissive cell becomes infected in the presence of a single infected cell in its neighborhood, a resistant cell needs to be surrounded by at least R>1 infected or dead cells in order to become infected. The infection is followed by the death of the cells resulting in ulcers whose forms may be dendritic (self-limited clusters) or amoeboid (percolating clusters) depending on the degree of resistance R of the resistant cells as well as on the density of permissive cells in the healthy tissue. We show that a phase transition between these two regime...

  19. Antiviral Action of Synthetic Stigmasterol Derivatives on Herpes Simplex Virus Replication in Nervous Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Erina Petrera

    2014-01-01

    Full Text Available Polyfunctionalized stigmasterol derivatives, (22S,23S-22,23-dihydroxystigmast-4-en-3-one (compound 1 and (22S,23S-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (compound 2, inhibit herpes simplex virus type 1 (HSV-1 replication and spreading in human epithelial cells derived from ocular tissues. Both compounds reduce the incidence and severity of lesions in a murine model of herpetic stromal keratitis when administered in different treatment modalities. Since encephalitis caused by HSV-1 is another immunopathology of viral origin, we evaluate here the antiviral effect of both compounds on HSV-1 infected nervous cell lines as well as their anti-inflammatory action. We found that both stigmasterol derivatives presented low cytotoxicity in the three nervous cell lines assayed. Regarding the antiviral activity, in all cases both compounds prevented HSV-1 multiplication when added after infection, as well as virus propagation. Additionally, both compounds were able to hinder interleukin-6 and Interferon-gamma secretion induced by HSV-1 infection in Neuro-2a cells. We conclude that compounds 1 and 2 have exerted a dual antiviral and anti-inflammatory effect in HSV-1 infected nervous cell lines, which makes them interesting molecules to be further studied.

  20. Functional analysis of transcriptional regulation of herpes simplex virus type 1 tegument protein VP22

    Institute of Scientific and Technical Information of China (English)

    YU Xian; LI WeiZhong; LIU LongDing; CHE YanChun; CUN Wei; WU Wen Juan; HE ChunYan; SHAO CongWen; LI QiHan

    2008-01-01

    The herpes simplex virus type 1 (HSV-1) tegument proteins have important functions in the viral repli-cation process. In order to investigate the role of the HSV-1 tegument protein VP22 in viral replication, its transcriptional regulation of viral promoters was investigated using the chloramphenicol acetyl-transferase (CAT) assay. The results indicate that VP22 exerts a dose-dependent transcriptional in-hibitory effect on the HSV-1 α4, TK, and gC gene promoters. VP22 had the capacity to repress tran-scriptional activation of promoters via different viral transcription regulatory factors such as VP16 and ICP0, as evidenced by the specific repression of the TK and gC gene promoters by ICP0. In addition, VP22 was capable of inhibiting the promotion of ICP0 transcriptional activation in the presence of HAT PCAF, which is even more remarkable than the VP22 repression of ICP0 transcriptional activation. Fi-nally, the transcriptional inhibitory effect of VP22 on other viral promoters was demonstrated by the analysis of β-galactosidase activities in internal controls.

  1. Herpes Simplex Virus-Type1 (HSV-1) Impairs DNA Repair in Cortical Neurons.

    Science.gov (United States)

    De Chiara, Giovanna; Racaniello, Mauro; Mollinari, Cristiana; Marcocci, Maria Elena; Aversa, Giorgia; Cardinale, Alessio; Giovanetti, Anna; Garaci, Enrico; Palamara, Anna Teresa; Merlo, Daniela

    2016-01-01

    Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer's disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions.

  2. Structural analysis of herpes simplex virus by optical super-resolution imaging.

    Science.gov (United States)

    Laine, Romain F; Albecka, Anna; van de Linde, Sebastian; Rees, Eric J; Crump, Colin M; Kaminski, Clemens F

    2015-01-22

    Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.

  3. Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells

    Indian Academy of Sciences (India)

    Goran Petrovski; Kata Pásztor; László Orosz; Réka Albert; Edina Mencel; Morten C Moe; Kai Kaarniranta; Andrea Facskó; Klára Megyeri

    2014-09-01

    Autophagy and apoptosis function as important early cellular defense mechanisms in infections and other diseases. The outcome of an infection is determined by a complex interplay between the pathogenic microorganism and these intracellular pathways. To better understand the cytopathogenicity of Herpes simplex virus types 1 and 2 (HSV-1 and - 2), we studied the effect of these viruses on the autophagic and apoptotic processes in the SIRC corneal cell line. Infection with the KOS strain of HSV-1 and a wild-type strain of HSV-2 enhanced autophagosome formation, triggered cytoplasmic acidification, increased LC3B lipidation and elevated the ratio of apoptotic cells. The autophagy inhibitor bafilomycin A1 triggered a significant increase in the apoptotic responses of HSV-1- and HSV-2-infected cells. Thus, both HSV types affect autophagy and apoptosis in a coordinated fashion, and autophagy plays cytoprotective role in HSV-infected cells via antagonizing apoptosis. Together these data implicate autophagy in the pathogenic mechanism of herpetic keratitis.

  4. Anti-herpes simplex virus activity of polysaccharides from Eucheuma gelatinae.

    Science.gov (United States)

    Jin, Fujun; Zhuo, Cuiqin; He, Zhe; Wang, Huailin; Liu, Wei; Zhang, Rong; Wang, Yifei

    2015-03-01

    Acyclovir is a commonly-used drug for treating herpes simplex virus (HSV) infections, but with its wide clinical application, more and more resistant strains have been found. Therefore, seeking a drug that can act against acyclovir-resistant virus has become an important goal of drug screening and development. In this study, plaque reduction assay, real-time PCR, Western blot, and immunofluorescence technique were used to investigate the antiviral effect of Eucheuma gelatinae polysaccharide (EGP) on HSV and to preliminarily clarify the in vitro anti-HSV mechanism of EGP. EGP was found to significantly inhibit HSV infection in vitro and displayed a good inhibitory effect on acyclovir-resistant strains. More detailed experiments have shown that EGP prevented early HSV-1 infection through directly inactivating HSV-1 particles and impairing virus attachment, but without effect on viral penetration. EGP also inhibited the RNA synthesis of HSV-1 early gene and late gene as well as viral DNA replication; no effect on immediate-early gene synthesis was observed. Besides, through immunofluorescence and western blot, we found that EGP significantly affected the protein synthesis of HSV-1. Taken together, these results demonstrate that EGP exerts its anti-HSV activity mainly through impeding early HSV-1 infection and inhibiting viral RNA and DNA syntheses. The weak cytotoxicity, strong viral inactivation as well as attachment inhibition activity enable EGP to be a virucide candidate for HSV therapy, especially for drug-resistant strains.

  5. Generation and characterization of UL21-null herpes simplex virus type 1

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    Yoshifumi eMuto

    2012-11-01

    Full Text Available UL21 of herpes simplex virus type 1 (HSV-1 is an accessory gene that encodes a component of the tegument. Homologs of this protein have been identified in the alpha, beta, and gamma herpesvirus subfamilies, although their functions are unclear. To clarify the functions of UL21, we generated a UL21-null HSV-1 mutant. Growth analysis showed that the synthesis of infectious UL21-null HSV-1 in glial cells was delayed and that the overall yield was low. The plaque sizes of the UL21-null mutant were smaller than those of wild-type HSV-1. We identified several candidate UL21-interacting proteins, including intermediate filaments, by yeast two-hybrid screening. The distribution of glial fibrillary acidic protein (GFAP, which is the main component of intermediate filaments, was altered in UL21-null mutant-infected glial cells compared to wild-type virus-infected cells. These results will help clarify the function of UL21 and broaden our understanding of the life cycle of HSV.

  6. A novel DNA vaccine technology conveying protection against a lethal herpes simplex viral challenge in mice.

    Directory of Open Access Journals (Sweden)

    Julie L Dutton

    Full Text Available While there are a number of licensed veterinary DNA vaccines, to date, none have been licensed for use in humans. Here, we demonstrate that a novel technology designed to enhance the immunogenicity of DNA vaccines protects against lethal herpes simplex virus 2 (HSV-2 challenge in a murine model. Polynucleotides were modified by use of a codon optimization algorithm designed to enhance immune responses, and the addition of an ubiquitin-encoding sequence to target the antigen to the proteasome for processing and to enhance cytotoxic T cell responses. We show that a mixture of these codon-optimized ubiquitinated and non-ubiquitinated constructs encoding the same viral envelope protein, glycoprotein D, induced both B and T cell responses, and could protect against lethal viral challenge and reduce ganglionic latency. The optimized vaccines, subcloned into a vector suitable for use in humans, also provided a high level of protection against the establishment of ganglionic latency, an important correlate of HSV reactivation and candidate endpoint for vaccines to proceed to clinical trials.

  7. Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma

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    Alicia M. Waters

    2016-10-01

    Full Text Available Rhabdomyosarcoma (RMS, a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these aggressive malignancies. Genetically engineered oncolytic viruses, such as herpes simplex virus-1 (HSV, are currently being explored as treatments for pediatric tumors. M002, an oncolytic HSV, has both copies of the γ134.5 gene deleted, enabling replication in tumor cells but thwarting infection of normal, postmitotic cells. We hypothesized that M002 would infect human RMS tumor cells and lead to decreased tumor cell survival in vitro and impede tumor growth in vivo. In the current study, we demonstrated that M002 could infect, replicate in, and decrease cell survival in both embryonal (ERMS and alveolar rhabdomyosarcoma (ARMS cells. Additionally, M002 reduced xenograft tumor growth and increased animal survival in both ARMS and ERMS. Most importantly, we showed for the first time that repeated dosing of oncolytic virus coupled with low-dose radiation provided improved tumor response in RMS. These findings provide support for the clinical investigation of oncolytic HSV in pediatric RMS.

  8. Effect of ultrasound on herpes simplex virus infection in cell culture

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    Iwai Soichi

    2011-09-01

    Full Text Available Abstract Background Ultrasound has been shown to increase the efficiency of gene expression from retroviruses, adenoviruses and adeno-associated viruses. The effect of ultrasound to stimulate cell membrane permeabilization on infection with an oncolytic herpes simplex virus type 1 (HSV-1 was examined. Results Vero monkey kidney cells were infected with HSV-1 and exposed to 1 MHz ultrasound after an adsorption period. The number of plaques was significantly greater than that of the untreated control. A combination of ultrasound and microbubbles further increased the plaque number. Similar results were obtained using a different type of HSV-1 and oral squamous cell carcinoma (SCC cells. The appropriate intensity, duty cycle and time of ultrasound to increase the plaque number were 0.5 W/cm2, 20% duty cycle and 10 sec, respectively. Ultrasound with microbubbles at an intensity of 2.0 W/cm2, at 50% duty cycle, or for 40 sec reduced cell viability. Conclusion These results indicate that ultrasound promotes the entry of oncolytic HSV-1 into cells. It may be useful to enhance the efficiency of HSV-1 infection in oncolytic virotherapy.

  9. Current Concepts for Genital Herpes Simplex Virus Infection: Diagnostics and Pathogenesis of Genital Tract Shedding

    Science.gov (United States)

    Corey, Lawrence

    2015-01-01

    SUMMARY Herpes simplex virus 2 (HSV-2) is a DNA virus that is efficiently transmitted through intimate genital tract contact and causes persistent infection that cannot be eliminated. HSV-2 may cause frequent, symptomatic self-limited genital ulcers, but in most persons infection is subclinical. However, recent studies have demonstrated that the virus is frequently shed from genital surfaces even in the absence of signs or symptoms of clinical disease and that the virus can be transmitted during these periods of shedding. Furthermore, HSV-2 shedding is detected throughout the genital tract and may be associated with genital tract inflammation, which likely contributes to increased risk of HIV acquisition. This review focuses on HSV diagnostics, as well as what we have learned about the importance of frequent genital HSV shedding for (i) HSV transmission and (ii) genital tract inflammation, as well as (iii) the impact of HSV-2 infection on HIV acquisition and transmission. We conclude with discussion of future areas of research to push the field forward. PMID:26561565

  10. Proteomic analysis of the herpes simplex virus 1 virion protein 16 transactivator protein in infected cells.

    Science.gov (United States)

    Suk, Hyung; Knipe, David M

    2015-06-01

    The herpes simplex virus 1 virion protein 16 (VP16) tegument protein forms a transactivation complex with the cellular proteins host cell factor 1 (HCF-1) and octamer-binding transcription factor 1 (Oct-1) upon entry into the host cell. VP16 has also been shown to interact with a number of virion tegument proteins and viral glycoprotein H to promote viral assembly, but no comprehensive study of the VP16 proteome has been performed at early times postinfection. We therefore performed a proteomic analysis of VP16-interacting proteins at 3 h postinfection. We confirmed the interaction of VP16 with HCF-1 and a large number of cellular Mediator complex proteins, but most surprisingly, we found that the major viral protein associating with VP16 is the infected cell protein 4 (ICP4) immediate-early (IE) transactivator protein. These results raise the potential for a new function for VP16 in associating with the IE ICP4 and playing a role in transactivation of early and late gene expression, in addition to its well-documented function in transactivation of IE gene expression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Structural analysis of herpes simplex virus by optical super-resolution imaging

    Science.gov (United States)

    Laine, Romain F.; Albecka, Anna; van de Linde, Sebastian; Rees, Eric J.; Crump, Colin M.; Kaminski, Clemens F.

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.

  12. Screening and identification of host factors interacting with UL14 of herpes simplex virus 1.

    Science.gov (United States)

    Wu, Fuqing; Xing, Junji; Wang, Shuai; Li, Meili; Zheng, Chunfu

    2011-08-01

    The UL14 protein of herpes simplex virus type 1 (HSV-1) is highly conserved in herpesvirus family. However, its exact function during the HSV-1 replication cycle is little known. In the present study, a high throughput yeast two-hybrid system was employed to screen the cellular factors interacting with UL14, and five target candidates were yielded: (1) TSC22 domain family protein 3 (TSC22D3); (2) Mediator of RNA polymerase II transcription subunit 8 isoform 1(MED8); (3) Runt-related transcription factor 3 (RUNX3); (4) Arrestin beta-2 (ARRB2); (5) Cereblon (CRBN). Indirect immunofluorescent assay showed that both TSC22D3 and MED8 co-localized with UL14. Co-immunoprecipitation assay demonstrated that UL14 could be immunoprecipitated by TSC22D3, suggesting that UL14 interacted with TSC22D3 under physiological condition. In summary, this study opened up new avenues toward delineating the function and physiological significance of UL14 during the HSV-1 replication cycle.

  13. Mathematical modeling of herpes simplex virus-2 suppression with pritelivir predicts trial outcomes

    Science.gov (United States)

    Schiffer, Joshua T.; Swan, David A.; Magaret, Amalia; Corey, Lawrence; Wald, Anna; Ossig, Joachim; Ruebsamen-Schaeff, Helga; Stoelben, Susanne; Timmler, Burkhard; Zimmermann, Holger; Melhem, Murad R.; Van Wart, Scott A.; Rubino, Christopher M.; Birkmann, Alexander

    2016-01-01

    Pharmacokinetic and pharmacodynamic models estimate the potency of antiviral agents but do not capture viral and immunologic factors that drive the natural dynamics of infection. We designed a mathematical model that synthesizes pharmacokinetics, pharmacodynamics and viral pathogenesis concepts to simulate the activity of pritelivir, a DNA helicase-primase inhibitor that targets herpes simplex virus. Our simulations recapitulate detailed viral kinetic shedding features in five dosage arms of a phase 2 clinical trial. We identify that in vitro estimates of EC50 are lower than in vivo values for the drug. Nevertheless, pritelivir potently decreases shedding at appropriate doses based on its mode of action and long half-life. While pritelivir directly inhibits replication in epithelial cells, our model indicates that pritelivir also indirectly limits downstream viral spread from neurons to genital keratinocytes, within genital ulcers, and from ulcer to new mucosal sites of infection. We validate our model based on its ability to predict outcomes in a subsequent trial with a higher dose. The model can therefore be employed to optimize dose selection in clinical practice. PMID:26843190

  14. Global and Regional Estimates of Prevalent and Incident Herpes Simplex Virus Type 1 Infections in 2012.

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    Katharine J Looker

    Full Text Available Herpes simplex virus type 1 (HSV-1 commonly causes orolabial ulcers, while HSV-2 commonly causes genital ulcers. However, HSV-1 is an increasing cause of genital infection. Previously, the World Health Organization estimated the global burden of HSV-2 for 2003 and for 2012. The global burden of HSV-1 has not been estimated.We fitted a constant-incidence model to pooled HSV-1 prevalence data from literature searches for 6 World Health Organization regions and used 2012 population data to derive global numbers of 0-49-year-olds with prevalent and incident HSV-1 infection. To estimate genital HSV-1, we applied values for the proportion of incident infections that are genital.We estimated that 3709 million people (range: 3440-3878 million aged 0-49 years had prevalent HSV-1 infection in 2012 (67%, with highest prevalence in Africa, South-East Asia and Western Pacific. Assuming 50% of incident infections among 15-49-year-olds are genital, an estimated 140 million (range: 67-212 million people had prevalent genital HSV-1 infection, most of which occurred in the Americas, Europe and Western Pacific.The global burden of HSV-1 infection is huge. Genital HSV-1 burden can be substantial but varies widely by region. Future control efforts, including development of HSV vaccines, should consider the epidemiology of HSV-1 in addition to HSV-2, and especially the relative contribution of HSV-1 to genital infection.

  15. Immunopathogenic Role of Herpes Simplex Virus in Behçet’s Disease

    Directory of Open Access Journals (Sweden)

    Do Young Kim

    2013-01-01

    Full Text Available The role of viral infections, such as herpes simplex virus (HSV infection, in the pathogenesis of Behçet’s disease (BD has been investigated for many years. HSV has been detected in peripheral blood leukocytes, saliva, and genital ulcers of patients with BD. Various cell adhesion molecules on cultured endothelial cells have been induced by HSV in a TNF-α dependent manner. In addition, a BD-like animal model was developed by inoculating ICR mouse earlobes with HSV, and antiviral treatment was effective in improving BD-like symptoms in this model. Still, there are several incompletely characterized proteins that possess antiviral properties and are being investigated as mediators of viral infection-related chronic inflammatory reactions. Although the role of HSV in the pathogenesis of BD remains to be fully established, recent research findings regarding HSV in BD have expanded our understanding of the disease and will hopefully lead to the development of more effective therapeutic agents in the near future.

  16. Molecular detection of cytomegalovirus, herpes simplex virus 2, human papillomavirus 16-18 in Turkish pregnants

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    Bedia Dinc

    2010-12-01

    Full Text Available OBJECTIVE: Human cytomegalovirus (CMV is the most common cause of viral intrauterine infections in the world. Herpes simplex virus type 2 (HSV-2 and human papillomavirus (HPV are the main agents of viral sexually transmitted diseases, which cause genital ulcers and genital warts, respectively. HPV infection has been linked to the majority of the anogenital malignancies. The aim of this study was to detect the existence of CMV, HSV-2 and HPV type 16-18 in Turkish pregnants by using sensitive molecular assays. METHODS: One hundred thirty-four women (18-41 years old; mean age ± SD: 27 ± 8 applied to outpatient clinic of Obstetrics and Gynecology, in between 18th - 22nd weeks of their pregnancy and a control group of 99 healthy women (15-39 years old; mean age ± SD: 24 ± 8 were included in the study. Cervical smear samples were used for DNA extraction. CMV, HSV-2 and HPV 16-18 detections were carried out by real time PCR and in house PCR method, respectively. RESULTS: Three patients (3/134; 2.2% were found to be positive for each HPV and HSV-2. Dual infection with HPV and HSV was found in just one patient. HPV 18 was detected in all positive samples. CMV was found to be positive in two patients (2/134; 1.4 %. CONCLUSION: HPV, HSV and CMV must be screened due to high prevalence of these viruses in pregnants by using sensitive molecular methods.

  17. Oncolytic herpes simplex virus vectors for the treatment of human breast cancer

    Institute of Scientific and Technical Information of China (English)

    LIU Ren-bin; Samuel D.Rabkin

    2005-01-01

    Background Oncolytic herpes simplex virus (HSV) vectors can be used for cancer therapy as direct cytotoxic agents, inducers of anti-tumor immune responses, and as expressers of anti-cancer genes. In this study, the efficacy of HSV vectors, G47Δ and NV1023 were examined for the treatment of the human breast cancer.Methods Human breast cancer MDA-MB-435 cells were cultured or implanted subcutaneously in BALB/c nude mice. The cells or tumors were inoculated with G47Δ or NV1023, and cell killing or inhibition of tumor growth determined. Both viruses contained the LacZ gene and expression in infected cells was detected with X-gal histochemistry. Results G47Δ and NV1023 were highly cytotoxic to MDA-MB-435 cells in vitro at very low multiplicities of infection. X-gal staining of infected tumor cells in vitro and in vivo illustrated the replication and spread of both viruses. G47Δ and NV1023 inoculation inhibited tumor growth and prolonged mouse survival. Both vectors behaved similarly.Conclusions Oncolytic HSV vectors, G47Δ and NV1023, were extremely effective at killing human breast cancer cells in vitro and in tumor xenografts in vivo. This novel form of cancer therapy warrants further investigation and consideration of clinical application.

  18. Molecular evaluation of extracellular activity of medicinal herb Clinacanthus nutans against herpes simplex virus type-2.

    Science.gov (United States)

    Vachirayonstien, Thaveechai; Promkhatkaew, Duanthanorm; Bunjob, Malee; Chueyprom, Asawachai; Chavalittumrong, Pranee; Sawanpanyalert, Pathom

    2010-02-01

    Clinacanthus nutans (Burm. f.) Lindau (C. nutans), a medicinal herb belonging to the family Acanthaceae, has traditionally been used in herpes simplex virus (HSV) treatment in Thailand. Clinical trials have indicated that topical preparations produced from its extracts were effective in HSV-2 treatment. However, there is no clear evidence of the mechanism of action or a molecular target of C. nutans. In this study, the extracellular activity of C. nutans extracts against HSV-2 infected on HEp-2 cells was investigated in terms of its molecular aspects. HSV-2 was treated with the extracts and adsorped into the HEp-2 cells. After infection, HSV-2 DNA quantities in the infected cells were assessed and compared by the quantitative dot blot hybridisation technique. The results showed that treating the viruses with either less or more highly purified extracts before infection resulted in great reductions of viral infectivity. Further investigation was performed by Western blot analysis to determine the activities of the extracts on the viral proteins. At least eight viral proteins of the infected cell proteins (ICP) and some structural proteins, including 146, 125, 78, 69, 55, 44, 40 and 20 KDa proteins, were depleted and reduced gradually with higher and lower concentrated herb extracts, respectively. These suggest that the C. nutans extracts highly inactivated or inhibited HSV-2 before infection.

  19. Association between unprotected ultraviolet radiation exposure and recurrence of ocular herpes simplex virus.

    Science.gov (United States)

    Ludema, Christina; Cole, Stephen R; Poole, Charles; Smith, Jennifer S; Schoenbach, Victor J; Wilhelmus, Kirk R

    2014-01-15

    Studies have suggested that exposure to ultraviolet (UV) light may increase risk of herpes simplex virus (HSV) recurrence. Between 1993 and 1997, the Herpetic Eye Disease Study (HEDS) randomized 703 participants with ocular HSV to receipt of acyclovir or placebo for prevention of ocular HSV recurrence. Of these, 308 HEDS participants (48% female and 85% white; median age, 49 years) were included in a nested study of exposures thought to cause recurrence and were followed for up to 15 months. We matched weekly UV index values from the National Oceanic and Atmospheric Administration to each participant's study center and used marginal structural Cox models to account for time-varying psychological stress and contact lens use and selection bias from dropout. There were 44 recurrences of ocular HSV, yielding an incidence of 4.3 events per 1,000 person-weeks. Weighted hazard ratios comparing persons with ≥8 hours of time outdoors to those with less exposure were 0.84 (95% confidence interval (CI): 0.27, 2.63) and 3.10 (95% CI: 1.14, 8.48) for weeks with a UV index of <4 and ≥4, respectively (ratio of hazard ratios = 3.68, 95% CI: 0.43, 31.4). Though results were imprecise, when the UV index was higher (i.e., ≥4), spending 8 or more hours per week outdoors was associated with increased risk of ocular HSV recurrence.

  20. Antiviral activity of extracts from Brazilian seaweeds against herpes simplex virus

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    Angélica Ribeiro Soares

    2012-08-01

    Full Text Available Organic extracts of 36 species of marine algae (sixteen species of Rhodophyta, eight species of Ochrophyta and twelve species of Chlorophyta from seven locations on the Brazilian coast were evaluated for their anti-HSV-1 and anti-HSV-2 activity resistant to Acyclovir (ACV. Activity tests in crude extracts, followed by the identification of the major compounds present, were performed for all species. The chemical profiles of all crude extracts were obtained by ¹H-NMR and 13C-NMR spectroscopy. The percentage of extracts with antiviral activity was higher for HSV-1 (86.1% than for HSV-2 (55.5%. The green algae Ulva fasciata and Codium decorticatum both showed the highest activity (99.9% against HSV-1, with triacylglycerols and fatty acids as the major components. The red alga Laurencia dendroidea showed good activity against HSV-1 (97.5% and the halogenated sesquiterpenes obtusol and (--elatol were identified as the major components in the extract. Against HSV-2, the green alga Penicillus capitatus (Chlorophyta and Stypopodium zonale (Ochrophyta were the most active (96.0 and 95.8%. Atomaric acid, a meroditerpene, was identified as the major secondary metabolite in the S. zonale extract. These results reinforce the role of seaweeds as important sources of compounds with the potential to enter into the pipeline for development of new drugs against herpes simplex.

  1. Houttuynia cordata targets the beginning stage of herpes simplex virus infection.

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    Pei-Yun Hung

    Full Text Available Herpes simplex virus (HSV, a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata, a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV.

  2. Herpes simplex virus thymidine kinase and ganciclovir suicide gene therapy for human pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Xiao-Xuan Lu; Dao-Zhen Chen; Shu-Feng Li; Li-Shan Zhang

    2004-01-01

    AIM: To investigate the in vitro effects of suicide gene therepy system of herpes simplex virus thymidine kinase gene (HSV-TK) in combination with the treatment of nucleotide analog-ganciclovir (GCV) on human pancreatic cancer, and to provide a novel clinical therapeutic method for human pancreatic cancer.METHODS: We used a replication defective recombinant retrovirus vector GINaTK (bearing HSV-TK gene) to make packaging cell PA317 produce progeny virions. We then transferred the HSV-TK gene to target cells SW1990 using these progeny virions, and treated these gene-modified tumor cells with GCV to study the sensitivity of the cells to GCV and their bystander effects by routine MTT-method.RESULTS: Packaging cell PA317/TK was successfully constructed, and we acquired SW1990/TK through virus progeny infection. These gene-modified pancreatic cancer cells were sensitive to the treatment of GCV compared with unmodified tumor cells (t=4.15, n=10, P<0.0025). We also observed a remarkable bystander effect by mixing two kinds of cells at different ratio.CONCLUSION: Our data demonstrate that HSV-TK/GCV suicide gene therapy system is effective for treating experimental human pancreatic cancer, which is largely resistant to the common therapies, so the suicide gene therapy system may be a potential treatment approach for pancreatic cancer.

  3. Highly reliable heterologous system for evaluating resistance of clinical herpes simplex virus isolates to nucleoside analogues.

    Science.gov (United States)

    Bestman-Smith, J; Schmit, I; Papadopoulou, B; Boivin, G

    2001-04-01

    Clinical resistance of herpes simplex virus (HSV) types 1 and 2 to acyclovir (ACV) is usually caused by the presence of point mutations within the coding region of the viral thymidine kinase (TK) gene. The distinction between viral TK mutations involved in ACV resistance or part of viral polymorphism can be difficult to evaluate with current methodologies based on transfection and homologous recombination. We have developed and validated a new heterologous system based on the expression of the viral TK gene by the protozoan parasite Leishmania, normally devoid of TK activity. The viral TK genes from 5 ACV-susceptible and 13 ACV-resistant clinical HSV isolates and from the reference strains MS2 (type 2) and KOS (type 1) were transfected as part of an episomal expression vector in Leishmania. The susceptibility of TK-recombinant parasites to ganciclovir (GCV), a closely related nucleoside analogue, was evaluated by a simple measurement of the absorbance of Leishmania cultures grown in the presence of the drug. Expression of the TK gene from ACV-susceptible clinical isolates resulted in Leishmania susceptibility to GCV, whereas expression of a TK gene with frameshift mutations or nucleotide substitutions from ACV-resistant isolates gave rise to parasites with high levels of GCV resistance. The expression of the HSV TK gene in Leishmania provides an easy, reliable, and sensitive assay for evaluating HSV susceptibility to nucleoside analogues and for assessing the role of specific viral TK mutations.

  4. Herpes simplex 1 stomatitis after cleft palate repair: a case report and guidelines for management.

    Science.gov (United States)

    Evangelista, Maristella S; Tracy, Lauren; Wells, James H

    2015-05-01

    Herpes simplex virus (HSV) primary infection and reactivation has been associated with the inflammation and transient decrease in immunocompetence after surgery and local trauma. In addition, HSV infection is known to impair wound healing, increase risk of scarring, and impede connective tissue graft transplantation. To our knowledge, this is the first case of HSV infection complicating cleft palate repair presented in literature. In this report, we present a case of primary HSV infection occurring in a healthy 26-month-old patient after repair of the secondary cleft palate with mucoperichondrial flaps and V-Y pushback. The patient developed high fever on postoperative day 1, which was followed by perioral vesicular lesions and multiple intraoral ulcerations involving the lips, palate, and posterior pharynx. Unknown to the surgeons, the patient was exposed to HSV before surgery by a sibling with orolabial HSV infection. The infective cause was ascertained via polymerase chain reaction for HSV-1 DNA, and the infection was treated with topical and intravenous acyclovir for 1 week. The patient recovered well with adequate flap healing, good aesthetic outcome, and no complications on 1-month follow-up. This report underscores the importance of prompt recognition of herpetic infections in the patient with craniofacial surgery and reviews the association and complications of HSV infection in surgical healing. Early identification with prompt antiviral therapy and meticulous wound care are essential to ameliorate the scarring and delayed wound healing associated with HSV infection.

  5. Entry of Oncolytic Herpes Simplex Virus into Human Squamous Cell Carcinoma Cells by Ultrasound

    Directory of Open Access Journals (Sweden)

    Shusuke Okunaga

    2015-10-01

    Full Text Available Low-intensity ultrasound is a useful method to introduce materials into cells due to the transient formation of micropores, called sonoporations, on the cell membrane. Whether oncolytic herpes simplex virus type 1 (HSV-1 can be introduced into oral squamous cell carcinoma (SCC cells through membrane pores remains undetermined. Human SCC cell line SAS and oncolytic HSV-1 RH2, which was deficient in the 134.5 gene and fusogenic, were used. Cells were exposed to ultrasound in the presence or absence of microbubbles. The increase of virus entry was estimated by plaque numbers. Viral infection was hardly established without the adsorption step, but plaque number was increased by the exposure of HSV-1-inoculated cells to ultrasound. Plaque number was also increased even if SAS cells were exposed to ultrasound and inoculated with RH2 without the adsorption step. This effect was abolished when the interval from ultrasound exposure to virus inoculation was prolonged. Scanning electron microscopy revealed depressed spots on the cell surface after exposure to ultrasound. These results suggest that oncolytic HSV-1 RH2 can be introduced into SAS cells through ultrasound-mediated pores of the cell membrane that are resealed after an interval.

  6. Early shutoff of host protein synthesis in cells infected with herpes simplex viruses.

    Science.gov (United States)

    Matis, J; Kúdelová, M

    2001-01-01

    Herpes simplex viruses 1 (HSV-1) and 2 (HSV-2) are capable of suppressing the host cell protein synthesis even without viral gene expression. This phenomenon is known as the early shutoff or as the virion-associated host shutoff (vhs) to emphasize that it is mediated by a component of infecting virions which is a product of the UL41 (vhs) gene. The UL41 encoded protein is a functional tegument protein also present in light (L) particles and is not essential for virus replication. The major product of UL41 gene is a 58 K phosphoprotein. At least two forms of UL41 protein differing in the extent of phosphorylation are present in HSV-1-infected cells. HSV-2 compared to HSV-1 strains display a stronger vhs phenotype. However, in superinfection experiments the less strong vhs phenotype is dominant. UL41 protein triggers disruption of polysomes and rapid degradation of all host and viral mRNAs and blocks a reporter gene expression without other HSVs proteins. The available evidence suggests that UL41 protein is either itself a ribonuclease (RNase) or a subunit of RNase that contains also one or more cellular subunits. UL41 protein is capable of interacting with a transactivator of an alpha-gene, the alpha-transinducing factor (alpha-TIF). Interaction of UL41 protein with alpha-TIF down regulates the UL41 (vhs) gene activity during lytic infection. The possible role of other viral proteins in the shutoff is discussed.

  7. Herpes simplex virus 1 counteracts tetherin restriction via its virion host shutoff activity.

    Science.gov (United States)

    Zenner, Helen L; Mauricio, Rui; Banting, George; Crump, Colin M

    2013-12-01

    The interferon-inducible membrane protein tetherin (Bst-2, or CD317) is an antiviral factor that inhibits enveloped virus release by cross-linking newly formed virus particles to the producing cell. The majority of viruses that are sensitive to tetherin restriction appear to be those that acquire their envelopes at the plasma membrane, although many viruses, including herpesviruses, envelope at intracellular membranes, and the effect of tetherin on such viruses has been less well studied. We investigated the tetherin sensitivity and possible countermeasures of herpes simplex virus 1 (HSV-1). We found that overexpression of tetherin inhibits HSV-1 release and that HSV-1 efficiently depletes tetherin from infected cells. We further show that the virion host shutoff protein (Vhs) is important for depletion of tetherin mRNA and protein and that removal of tetherin compensates for defects in replication and release of a Vhs-null virus. Vhs is known to be important for HSV-1 to evade the innate immune response in vivo. Taken together, our data suggest that tetherin has antiviral activity toward HSV-1 and that the removal of tetherin by Vhs is important for the efficient replication and dissemination of HSV-1.

  8. The Effect of Cumin Seed Extracts against Herpes Simplex Virus Type 1 in Vero Cell Culture

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    Mohammad Motamedifar

    2010-12-01

    Full Text Available Background: Cumin (Cuminum cyminum L. [family Apiaceae]seed essential oil is reported to have antiseptic activity.Until now the antiviral properties of cumin seed extracts onviruses such as herpes simplex virus-1 (HSV-1 have not beenstudied. The objective of this study was to investigate the invitro effects of aqueous, methanolic and hydroalcoholic extractsof cumin seed on HSV-1 growth in Vero cell line.Methods: Antiviral activity of various concentrations aqueous,hydroalcoholic and methanolic extracts of cumin seed in Verocells were studied using plaque reduction assays. The 50%cytotoxic concentration (CC50, 50% inhibitory concentration(IC50, and therapeutic index of the effective extracts were calculated.Results: Methanolic extract of cumin seed showed a significantantiviral activity on HSV-1 in Vero cell line. Its CC50 forVero cells, IC50 and the therapeutic index for HSV-1 were0.45, 0.18 mg/mL and 2.5, respectively. Aqueous and hydroalcoholicextracts of cumin seeds showed no inhibitory effecton HSV-1.Conclusion: The methanolic extract of cumin seed producesanti-HSV-1 effect. Probable interference of phenolic compoundswith fusion of Vero cell membrane and HSV-1 envelopemight be the mechanism of such inhibitory effect. Furtherstudies are required to ascertain its in vivo antiviral propertiesand potential toxicity.Iran J Med Sci 2010; 35(4: 304-309.

  9. Recombinant herpes simplex virus type 1 strains with targeted mutations relevant for aciclovir susceptibility

    Science.gov (United States)

    Brunnemann, Anne-Kathrin; Liermann, Kristin; Deinhardt-Emmer, Stefanie; Maschkowitz, Gregor; Pohlmann, Anja; Sodeik, Beate; Fickenscher, Helmut; Sauerbrei, Andreas; Krumbholz, Andi

    2016-01-01

    Here, we describe a novel reliable method to assess the significance of individual mutations within the thymidine kinase (TK) gene of herpes simplex virus type 1 (HSV-1) to nucleoside analogue resistance. Eleven defined single nucleotide polymorphisms that occur in the TK gene of clinical HSV-1 isolates and a fluorescence reporter were introduced into the HSV-1 strain 17+ that had been cloned into a bacterial artificial chromosome. The susceptibility of these different strains to aciclovir, penciclovir, brivudin, and foscarnet was determined with a modified cytopathic effect reduction assay. The strains were also tested for their aciclovir susceptibility by measuring the relative fluorescence intensity as an indicator for HSV-1 replication and by quantifying the virus yield. Our data indicate that the amino acid substitutions R41H, R106H, A118V, L139V, K219T, S276R, L298R, S345P, and V348I represent natural polymorphisms of the TK protein, whereas G61A and P84L mediate broad cross-resistance against aciclovir, penciclovir, brivudin, and susceptibility to foscarnet. This method allows the definition of the resistance genotype of otherwise unclear mutations in the TK gene of HSV-1. Thus, it provides a scientific basis for antiviral testing in clinical isolates of patients suffering from serious diseases and will facilitate testing of new antivirals against HSV-1. PMID:27426251

  10. DNA replication catalyzed by herpes simplex virus type 1 proteins reveals trombone loops at the fork.

    Science.gov (United States)

    Bermek, Oya; Willcox, Smaranda; Griffith, Jack D

    2015-01-30

    Using purified replication factors encoded by herpes simplex virus type 1 and a 70-base minicircle template, we obtained robust DNA synthesis with leading strand products of >20,000 nucleotides and lagging strand fragments from 600 to 9,000 nucleotides as seen by alkaline gel electrophoresis. ICP8 was crucial for the synthesis on both strands. Visualization of the deproteinized products using electron microscopy revealed long, linear dsDNAs, and in 87%, one end, presumably the end with the 70-base circle, was single-stranded. The remaining 13% had multiple single-stranded segments separated by dsDNA segments 500 to 1,000 nucleotides in length located at one end. These features are diagnostic of the trombone mechanism of replication. Indeed, when the products were examined with the replication proteins bound, a dsDNA loop was frequently associated with the replication complex located at one end of the replicated DNA. Furthermore, the frequency of loops correlated with the fraction of DNA undergoing Okazaki fragment synthesis.

  11. Unusual progression of herpes simplex encephalitis with basal ganglia and extensive white matter involvement

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    Yasuhiro Manabe

    2009-08-01

    Full Text Available We report a 51-year old male with herpes simplex encephalitis (HSE showing unusual progression and magnetic resonance (MR findings. The initial neurological manifestation of intractable focal seizure with low-grade fever persisted for three days, and rapidly coma, myoclonic status, and respiratory failure with high-grade fever emerged thereafter. The polymerase chain reaction (PCR result of cerebrospinal fluid (CSF was positive for HSV-1 DNA. In the early stage, MR images (MRI were normal. On subsequent MR diffusion-weighted (DW and fluid-attenuated inversion recovery (FLAIR images, high-intensity areas first appeared in the left frontal cortex, which was purely extra-temporal involvement, and extended into the basal ganglia, then the white matter, which are relatively spared in HSE. Antiviral therapy and immunosuppressive therapy did not suppress the progression of HSE, and finally severe cerebral edema developed into cerebral herniation, which required emergency decompressive craniectomy. Histological examination of a biopsy specimen of the white matter detected perivascular infiltration and destruction of basic structure, which confirmed non specific inflammatory change without obvious edema or demyelination. The present case shows both MR and pathological findings in the white matter in the acute stage of HSE.

  12. Anti-herpes simplex virus activities of crude water extracts of Thai medicinal plants.

    Science.gov (United States)

    Yoosook, C; Bunyapraphatsara, N; Boonyakiat, Y; Kantasuk, C

    2000-01-01

    A number of Thai medicinal plants, recommended as remedies for herpesvirus infection and have been used in primary health care were investigated for their intracellular activities against herpes simplex viruses (HSV). Centella asiatica L., Maclura cochinchinensis Cornor, and Mangifera indica L. contained both anti-HSV-1 and -2 activities, as determined by plaque inhibition assay. An inhibition of the production of infectious HSV-2 virions from infected Vero cells could also be demonstrated. Combinations of each of these reconstituted extracts with 9-(2-hydroxyethoxymethyl) guanosine (acyclovir; ACV) resulted either in subadditive, additive, or synergistic interaction, against HSV-2, depending on the dose of ACV used; mixture of C. asiatica and M. indica exerted an additive effect in a similar assay. Furthermore, the inhibitory effects of these plant extracts were also substantiated by flow cytometric analysis of virus-specific antigens in the infected cells. The active constituent present in C. asiatica extract was determined to be asiaticoside while in M. indica was mangiferin. Thus, these data suggest therapeutic potential of these plant extracts.

  13. Alzheimer's Disease: A Pathogenetic Autoimmune Disorder Caused by Herpes Simplex in a Gene-Dependent Manner

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    C. J. Carter

    2010-01-01

    Full Text Available Herpes simplex is implicated in Alzheimer's disease and viral infection produces Alzheimer's disease like pathology in mice. The virus expresses proteins containing short contiguous amino acid stretches (5–9aa “vatches” = viralmatches homologous to APOE4, clusterin, PICALM, and complement receptor 1, and to over 100 other gene products relevant to Alzheimer's disease, which are also homologous to proteins expressed by other pathogens implicated in Alzheimer's disease. Such homology, reiterated at the DNA level, suggests that gene association studies have been tracking infection, as well as identifying key genes, demonstrating a role for pathogens as causative agents. Vatches may interfere with the function of their human counterparts, acting as dummy ligands, decoy receptors, or via interactome interference. They are often immunogenic, and antibodies generated in response to infection may target their human counterparts, producing protein knockdown, or generating autoimmune responses that may kill the neurones in which the human homologue resides, a scenario supported by immune activation in Alzheimer's disease. These data may classify Alzheimer's disease as an autoimmune disorder created by pathogen mimicry of key Alzheimer's disease-related proteins. It may well be prevented by vaccination and regular pathogen detection and elimination, and perhaps stemmed by immunosuppression or antibody adsorption-related therapies.

  14. Selective inhibition of herpes simplex virus glycoprotein synthesis by a benz-amidinohydrazone derivative

    Energy Technology Data Exchange (ETDEWEB)

    Campadelli-Fiume, G.; Sinibaldi-Vallebona, P.; Mannini-Palenzona, A. (Bologna Univ. (Italy). Ist. di Microbiologia e Virologia); Cavrini, V. (Bologna Univ. (Italy). Ist. di Chimica Farmaceutica e Tossicologica)

    1980-01-01

    1 H-benz(f)indene-1.3(2H)dione-bis-amidinohydrazone (benzhydrazone) inhibited incorporation of /sup 14/C-glucosamine, /sup 14/C-fucose and /sup 14/C-mannose into glycoproteins of HEp-2 cells infected with various strains of herpes simplex virus 1 (HSV-1) and impaired RNA and protein synthesis to a low extent. These biochemical effects are very similar to those induced by glycosylation inhibitors such as tunicamycin, D-glucosamine and 2-deoxy-D-glucose. In contrast to these inhibitors, benzhydrazone reduced HSV glycoprotein synthesis selectively since it did not significantly modify i) the saccharide uptake into glycoproteins of uninfected and of Sindbis virus-infected cells, ii) viral growth and cell fusion in paramyxovirus-infected cells, two activities which depend on viral glycoprotein synthesis. Benzhydrazone had only minor effects on the overall metabolism of uninfected cells, since it did not alter cell growth rate, and amino acid, uridine, and hexose incorporations were about 80 per cent those of untreated cells.

  15. Induction of Cervical Neoplasia in the Mouse by Herpes Simplex Virus Type 2 DNA

    Science.gov (United States)

    Anthony, Donald D.; Budd Wentz, W.; Reagan, James W.; Heggie, Alfred D.

    1989-06-01

    Induction of cervical neoplasia in the mouse cervix by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) has been reported. The present study was done to determine if transfection with DNA of HSV-2 can induce carcinogenesis in this animal model. Genomic HSV-2 DNA was isolated from infected HEp-2 cells and separated from host cell DNA by cesium chloride density gradient centrifugation. The DNA was applied to mouse cervix for periods of 80-100 weeks. Experimental controls were treated with uninfected genomic HEp-2 cell DNA or with calf thymus DNA. Vaginal cytological preparations from all animals were examined monthly to detect epithelial abnormalities. Animals were sacrificed and histopathology studies were done when cellular changes indicative of premalignant or malignant lesions were seen on vaginal smears. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from animals treated with virus or control DNA. Premalignant and malignant cervical lesions similar to those that occur in women were detected in 61% of the histologic specimens obtained from animals exposed to HSV-2 DNA. The yield of invasive cancers was 21% in animals treated with HSV-2 DNA. No cancers were detected in mice treated with either HEp-2 or calf thymus DNA. Dysplasia was detected in only one of these control animals.

  16. Targeting the central nervous system with herpes simplex virus / Sleeping Beauty hybrid amplicon vectors.

    Science.gov (United States)

    de Silva, Suresh; Bowers, William J

    2011-10-01

    The pursuits of sustainable treatments for diseases and disorders that afflict the central nervous system (CNS) have proven challenging for the field of viral vector-based gene therapy. However, recent advances in viral vector technology coupled with efficient delivery methods have opened up new avenues that show promise at the preclinical testing stage. The development of the Herpes Simplex Virus/Sleeping Beauty (HSV/SB) hybrid vector represents such an advance for devising treatments targeting the CNS with its potential for stably integrating large transgenomic segments of DNA within the genomes of transduced cells. In utero administration of this hybrid vector into the embryonic mouse brain has revealed the capacity for widespread transgene dissemination due to the targeting of a neuronal precursor cell population. This unique feature has provided the means to stably express a transgene throughout the brain for prolonged periods, which is a prerequisite for the treatment of progressive CNS disorders. In this review we provide a comprehensive breakdown of the characteristics of the HSV/SB vector system and how it can be efficiently employed in the derivation of CNS-targeted gene therapeutic strategies.

  17. Nelfinavir impairs glycosylation of herpes simplex virus 1 envelope proteins and blocks virus maturation.

    Science.gov (United States)

    Gantt, Soren; Gachelet, Eliora; Carlsson, Jacquelyn; Barcy, Serge; Casper, Corey; Lagunoff, Michael

    2015-01-01

    Nelfinavir (NFV) is an HIV-1 aspartyl protease inhibitor that has numerous effects on human cells, which impart attractive antitumor properties. NFV has also been shown to have in vitro inhibitory activity against human herpesviruses (HHVs). Given the apparent absence of an aspartyl protease encoded by HHVs, we investigated the mechanism of action of NFV herpes simplex virus type 1 (HSV-1) in cultured cells. Selection of HSV-1 resistance to NFV was not achieved despite multiple passages under drug pressure. NFV did not significantly affect the level of expression of late HSV-1 gene products. Normal numbers of viral particles appeared to be produced in NFV-treated cells by electron microscopy but remain within the cytoplasm more often than controls. NFV did not inhibit the activity of the HSV-1 serine protease nor could its antiviral activity be attributed to inhibition of Akt phosphorylation. NFV was found to decrease glycosylation of viral glycoproteins B and C and resulted in aberrant subcellular localization, consistent with induction of endoplasmic reticulum stress and the unfolded protein response by NFV. These results demonstrate that NFV causes alterations in HSV-1 glycoprotein maturation and egress and likely acts on one or more host cell functions that are important for HHV replication.

  18. Preclinical evaluation of engineered oncolytic herpes simplex virus for the treatment of neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Lauren A Gillory

    Full Text Available Despite intensive research efforts and therapeutic advances over the last few decades, the pediatric neural crest tumor, neuroblastoma, continues to be responsible for over 15% of pediatric cancer deaths. Novel therapeutic options are needed for this tumor. Recently, investigators have shown that mice with syngeneic murine gliomas treated with an engineered, neuroattenuated oncolytic herpes simplex virus-1 (oHSV, M002, had a significant increase in survival. M002 has deletions in both copies of the γ 1 34.5 gene, enabling replication in tumor cells but precluding infection of normal neural cells. We hypothesized that M002 would also be effective in the neural crest tumor, neuroblastoma. We showed that M002 infected, replicated, and decreased survival in neuroblastoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly decreased tumor growth, and that this effect was augmented with the addition of ionizing radiation. Importantly, survival could be increased by subsequent doses of radiation without re-dosing of the virus. Finally, these studies showed that the primary entry protein for oHSV, CD111 was expressed by numerous neuroblastoma cell lines and was also present in human neuroblastoma specimens. We concluded that M002 effectively targeted neuroblastoma and that this oHSV may have potential for use in children with unresponsive or relapsed neuroblastoma.

  19. Dependence of herpes simplex virus type 1-induced cell fusion on cell type

    Energy Technology Data Exchange (ETDEWEB)

    Bzik, D.J.; Person, S.

    1981-04-15

    Syncytial mutants of herpes simplex virus type 1 (HSV-1), such as syn20, cause extensive fusion of human embryonic lung (HEL) cells but only a small amount of fusion of human epidermoid carcinoma No. 2 (HEp-2) cells. In order to determine the cellular basis of this difference in fusion, sparse cultures of syn20-infected HEL or HEp-2 cells, previously labeled with (/sup 3/H)thymidine, were surrounded with uninfected, unlabeled HEL or HEp-2 cells. The fusion of radioactive with nonradioactive cells was determined at different times after infection using radioautography. The major difference in the fusion capacity of HEL and HEp-2 cells was not due to a difference in cell-surface receptors for a fusion factor in the two cell types. The process of infection of HEp-2 cells did not cause the plasma membranes of the cells to become refractory to fusion, because syn20-infected HEL cells fused equally well with either uninfected or infected HEp-2 cells. In a mixed infection with equal numbers of MP and its nonsyncytial parent, mP, extensive fusion was observed for infected HEL cells and significantly less fusion was observed for infected African green monkey (CV-1), baby hamster kidney (BHK-21), and HEp-2 cells.

  20. Poly(ADP-ribosyl)ation of a herpes simplex virus immediate early polypeptide

    Energy Technology Data Exchange (ETDEWEB)

    Preston, C.M.; Notarianni, E.L.

    1983-12-01

    In vitro poly(ADP-ribosyl)ation of the herpes simplex virus type 1 (HSV-1) immediate early polypeptide Vmw175 is reported. The phenomenon was most clearly observed by use of the temperature-sensitive mutant tsK, which overproduces Vmw175 at the nonpermissive temperature (NPT) and has a mutation in the coding sequences for this polypeptide. Nuclei prepared from cells which were infected with tsK at NPT and subsequently downshifted to the permissive temperature incorporated (/sup 32/P)NAD into Vmw175. This reaction did not occur when nuclei were prepared from cells constantly maintained at NPT, showing that only functional Vmw175 can be radiolabeled with (/sup 32/P)NAD. The identity of the acceptor protein was confirmed by demonstrating the expected electrophoretic mobility differences between the HSV-1 and HSV-2 counterparts of Vmw175. The use of suitable inhibitors demonstrated that the reaction represented mono- or poly(ADP-ribosyl)ation, and further analysis showed the presence of long poly(ADP-ribose) chains attached to Vmw175. Poly(ADP-ribosyl)ation may be important as a cause or result of the regulation of viral transcription by Vmw175. Radiolabeling of another virus-specified polypeptide (approximate molecular weight 38,000), thought to be a structural component of the input virus, is also reported.

  1. Involvement of intracellular free Ca2+ in enhanced release of herpes simplex virus by hydrogen peroxide

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    Ogawa Yuzo

    2006-08-01

    Full Text Available Abstract Background It was reported that elevation of the intracellular concentration of free Ca2+ ([Ca2+]i by a calcium ionophore increased the release of herpes simplex virus type 1 (HSV-1. Freely diffusible hydrogen peroxide (H2O2 is implied to alter Ca2+ homeostasis, which further enhances abnormal cellular activity, causing changes in signal transduction, and cellular dysfunction. Whether H2O2 could affect [Ca2+]i in HSV-1-infected cells had not been investigated. Results H2O2 treatment increased the amount of cell-free virus and decreased the proportion of viable cells. After the treatment, an elevation in [Ca2+]i was observed and the increase in [Ca2+]i was suppressed when intracellular and cytosolic Ca2+ were buffered by Ca2+ chelators. In the presence of Ca2+ chelators, H2O2-mediated increases of cell-free virus and cell death were also diminished. Electron microscopic analysis revealed enlarged cell junctions and a focal disintegration of the plasma membrane in H2O2-treated cells. Conclusion These results indicate that H2O2 can elevate [Ca2+]i and induces non-apoptotic cell death with membrane lesions, which is responsible for the increased release of HSV-1 from epithelial cells.

  2. Roles of TRIM32 in Corneal Epithelial Cells After Infection with Herpes Simplex Virus

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    Hao Cui

    2017-09-01

    Full Text Available Background: Epithelial cells play important roles as a critical barrier in protecting the cornea from microbial pathogens infection. Methods: In this study, we were aiming to investigate the role of E3 ubiquitin ligase tripartite motif protein 32 (TRIM32 in corneal epithelial cells in response to Herpes Simplex Virus type 1 (HSV-1 infection and to elucidate the underlying mechanisms. Results: We found the expression of TRIM32 was increased after infected with HSV-1 both in murine corneas and cultured human epithelial (HCE cells. Furthermore, knockdown of the expression of TRIM32 significantly aggravated HSV-1 induced herpetic stromal keratitis (HSK in mice and promoted the replication of HSV-1 in cultured HCE cells. We also observed that silencing of TRIM32 resulted in the decreased expression of IFN-β and suppressed activation of interferon regulatory factor 3 (IRF3 both in vivo and in vitro. Finally, we found TRIM32 positively regulate IFN-β production in corneal epithelial cells through promoting K63-linked polyubiquitination of stimulator of interferon genes (STING. Conclusion: In conclusion, our data suggested that TRIM32 as a crucial positive regulator of HSV-1 induced IFN-β production in corneal epithelial cells, and it played a predominant role in clearing HSV-1 from the cornea.

  3. Preclinical evaluation of engineered oncolytic herpes simplex virus for the treatment of pediatric solid tumors.

    Directory of Open Access Journals (Sweden)

    Michael L Megison

    Full Text Available Recently, investigators showed that mice with syngeneic murine gliomas that were treated with a neuroattenuated oncolytic herpes simplex virus-1 (oHSV, M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal cells. Previous studies have shown antitumor effects of other oHSV against a number of adult tumors including hepatocellular carcinoma and renal cell carcinoma. The purpose of the current study was to investigate the oncolytic potential of M002 against difficult to treat pediatric liver and kidney tumors. We showed that the oHSV, M002, infected, replicated, and decreased cell survival in hepatoblastoma, malignant rhabdoid kidney tumor, and renal sarcoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly increased survival and decreased tumor growth. Finally, these studies showed that the primary entry protein for oHSV, CD111 (nectin-1 was present in human hepatoblastoma and malignant rhabdoid kidney tumor specimens. We concluded that M002 effectively targeted these rare aggressive tumor types and that M002 may have potential for use in children with unresponsive or relapsed pediatric solid tumors.

  4. Preclinical Evaluation of Engineered Oncolytic Herpes Simplex Virus for the Treatment of Neuroblastoma

    Science.gov (United States)

    Gillory, Lauren A.; Megison, Michael L.; Stewart, Jerry E.; Mroczek-Musulman, Elizabeth; Nabers, Hugh C.; Waters, Alicia M.; Kelly, Virginia; Coleman, Jennifer M.; Markert, James M.; Gillespie, G. Yancey; Friedman, Gregory K.; Beierle, Elizabeth A.

    2013-01-01

    Despite intensive research efforts and therapeutic advances over the last few decades, the pediatric neural crest tumor, neuroblastoma, continues to be responsible for over 15% of pediatric cancer deaths. Novel therapeutic options are needed for this tumor. Recently, investigators have shown that mice with syngeneic murine gliomas treated with an engineered, neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal neural cells. We hypothesized that M002 would also be effective in the neural crest tumor, neuroblastoma. We showed that M002 infected, replicated, and decreased survival in neuroblastoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly decreased tumor growth, and that this effect was augmented with the addition of ionizing radiation. Importantly, survival could be increased by subsequent doses of radiation without re-dosing of the virus. Finally, these studies showed that the primary entry protein for oHSV, CD111 was expressed by numerous neuroblastoma cell lines and was also present in human neuroblastoma specimens. We concluded that M002 effectively targeted neuroblastoma and that this oHSV may have potential for use in children with unresponsive or relapsed neuroblastoma. PMID:24130898

  5. Preclinical Evaluation of Engineered Oncolytic Herpes Simplex Virus for the Treatment of Pediatric Solid Tumors

    Science.gov (United States)

    Megison, Michael L.; Gillory, Lauren A.; Stewart, Jerry E.; Nabers, Hugh C.; Mroczek-Musulman, Elizabeth; Waters, Alicia M.; Coleman, Jennifer M.; Kelly, Virginia; Markert, James M.; Gillespie, G. Yancey; Friedman, Gregory K.; Beierle, Elizabeth A.

    2014-01-01

    Recently, investigators showed that mice with syngeneic murine gliomas that were treated with a neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal cells. Previous studies have shown antitumor effects of other oHSV against a number of adult tumors including hepatocellular carcinoma and renal cell carcinoma. The purpose of the current study was to investigate the oncolytic potential of M002 against difficult to treat pediatric liver and kidney tumors. We showed that the oHSV, M002, infected, replicated, and decreased cell survival in hepatoblastoma, malignant rhabdoid kidney tumor, and renal sarcoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly increased survival and decreased tumor growth. Finally, these studies showed that the primary entry protein for oHSV, CD111 (nectin-1) was present in human hepatoblastoma and malignant rhabdoid kidney tumor specimens. We concluded that M002 effectively targeted these rare aggressive tumor types and that M002 may have potential for use in children with unresponsive or relapsed pediatric solid tumors. PMID:24497984

  6. pH Reduction as a Trigger for Dissociation of Herpes Simplex Virus Type 1 Scaffolds

    Science.gov (United States)

    McClelland, David A.; Aitken, James D.; Bhella, David; McNab, David; Mitchell, Joyce; Kelly, Sharon M.; Price, Nicholas C.; Rixon, Frazer J.

    2002-01-01

    Assembly of the infectious herpes simplex virus type 1 virion is a complex, multistage process that begins with the production of a procapsid, which is formed by the condensation of capsid shell proteins around an internal scaffold fashioned from multiple copies of the scaffolding protein, pre-VP22a. The ability of pre-VP22a to interact with itself is an essential feature of this process. However, this self-interaction must subsequently be reversed to allow the scaffolding proteins to exit from the capsid to make room for the viral genome to be packaged. The nature of the process by which dissociation of the scaffold is accomplished is unknown. Therefore, to investigate this process, the properties of isolated scaffold particles were investigated. Electron microscopy and gradient sedimentation studies showed that the particles could be dissociated by low concentrations of chaotropic agents and by moderate reductions in pH (from 7.2 to 5.5). Fluorescence spectroscopy and circular dichroism analyses revealed that there was relatively little change in tertiary and secondary structures under these conditions, indicating that major structural transformations are not required for the dissociation process. We suggest the possibility that dissociation of the scaffold may be triggered by a reduction in pH brought about by the entry of the viral DNA into the capsid. PMID:12097553

  7. Vulvar carcinomas: search for sequences homologous to human papillomavirus and herpes simplex virus DNA.

    Science.gov (United States)

    Pilotti, S; Rotola, A; D'Amato, L; Di Luca, D; Shah, K V; Cassai, E; Rilke, F

    1990-07-01

    Ten cases of intraepithelial carcinoma, five with Bowenoid features and five with early invasion, and ten cases of invasive vulvar carcinoma were examined by in situ hybridization and Southern blot analysis using DNA probes for human papillomavirus (HPV) types 6, 11, 16, 18 and 31. HPV DNA was detected in 90% of the intraepithelial cases and in 10% of the invasive cases. All positive cases showed the presence of DNA of HPV type 16. The cases with intraepithelial lesions revealed a strong correlation between the presence of HPV type 16 DNA, cigarette smoking habit, other potential cofactors such as herpes simplex (HSV) DNA sequences and the use of contraceptive drugs, and clinicopathologic features of Bowen's type in situ squamous cell carcinoma. Similar associations were not observed among the cases with invasive disease. While HPV-16 is associated with differentiated Bowenoid type vulvar intraepithelial neoplasia, which appears to be the most common form of early carcinoma of the vulva, the same association was not seen with respect to advanced vulvar invasive squamous cell carcinoma.

  8. Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation

    Directory of Open Access Journals (Sweden)

    Soren Gantt

    2015-01-01

    Full Text Available Nelfinavir (NFV is an HIV-1 aspartyl protease inhibitor that has numerous effects on human cells, which impart attractive antitumor properties. NFV has also been shown to have in vitro inhibitory activity against human herpesviruses (HHVs. Given the apparent absence of an aspartyl protease encoded by HHVs, we investigated the mechanism of action of NFV herpes simplex virus type 1 (HSV-1 in cultured cells. Selection of HSV-1 resistance to NFV was not achieved despite multiple passages under drug pressure. NFV did not significantly affect the level of expression of late HSV-1 gene products. Normal numbers of viral particles appeared to be produced in NFV-treated cells by electron microscopy but remain within the cytoplasm more often than controls. NFV did not inhibit the activity of the HSV-1 serine protease nor could its antiviral activity be attributed to inhibition of Akt phosphorylation. NFV was found to decrease glycosylation of viral glycoproteins B and C and resulted in aberrant subcellular localization, consistent with induction of endoplasmic reticulum stress and the unfolded protein response by NFV. These results demonstrate that NFV causes alterations in HSV-1 glycoprotein maturation and egress and likely acts on one or more host cell functions that are important for HHV replication.

  9. Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity

    Energy Technology Data Exchange (ETDEWEB)

    Knipe, David M., E-mail: david_knipe@hms.harvard.edu

    2015-05-15

    Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. HSV viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related. - Highlights: • HSV lytic and latent gene expression is regulated differentially by epigenetic processes. • The sensors of foreign DNA have not been defined fully. • IFI16 and cGAS cooperate to sense viral DNA in HSV-infected cells. • IFI16 plays a role in both innate sensing of HSV DNA and in restricting its expression.

  10. The herpes simplex virus 1 U{sub S}3 regulates phospholipid synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Wild, Peter, E-mail: pewild@access.uzh.ch [Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Institute of Virology, University of Zuerich (Switzerland); Oliveira, Anna Paula de [Institute of Virology, University of Zuerich (Switzerland); Sonda, Sabrina [Institute for Parasitology, University of Zuerich (Switzerland); Schraner, Elisabeth M. [Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Institute of Virology, University of Zuerich (Switzerland); Ackermann, Mathias; Tobler, Kurt [Institute of Virology, University of Zuerich (Switzerland)

    2012-10-25

    Herpes simplex virus type 1 capsids bud at nuclear and Golgi membranes for envelopment by phospholipid bilayers. In the absence of U{sub S}3, nuclear membranes form multiple folds harboring virions that suggests disturbance in membrane turnover. Therefore, we investigated phospholipid metabolism in cells infected with the U{sub S}3 deletion mutant R7041({Delta}U{sub S}3), and quantified membranes involved in viral envelopment. We report that (i) [{sup 3}H]-choline incorporation into nuclear membranes and cytoplasmic membranes was enhanced peaking at 12 or 20 h post inoculation with wild type HSV-1 and R7041({Delta}U{sub S}3), respectively, (ii) the surface area of nuclear membranes increased until 24 h of R7041({Delta}U{sub S}3) infection forming folds that equaled {approx}45% of the nuclear surface, (iii) the surface area of viral envelopes between nuclear membranes equaled {approx}2400 R7041({Delta}U{sub S}3) virions per cell, and (iv) during R7041({Delta}U{sub S}3) infection, the Golgi complex expanded dramatically. The data indicate that U{sub S}3 plays a significant role in regulation of membrane biosynthesis.

  11. Pediatric cancer gone viral. Part I: strategies for utilizing oncolytic herpes simplex virus-1 in children

    Directory of Open Access Journals (Sweden)

    Timothy P Cripe

    2015-01-01

    Full Text Available Progress for improving outcomes in pediatric patients with solid tumors remains slow. In addition, currently available therapies are fraught with numerous side effects, often causing significant life-long morbidity for long-term survivors. The use of viruses to kill tumor cells based on their increased vulnerability to infection is gaining traction, with several viruses moving through early and advanced phase clinical testing. The prospect of increased efficacy and decreased toxicity with these agents is thus attractive for pediatric cancer. In part I of this two-part review, we focus on strategies for utilizing oncolytic engineered herpes simplex virus (HSV to target pediatric malignancies. We discuss mechanisms of action, routes of delivery, and the role of preexisting immunity on antitumor efficacy. Challenges to maximizing oncolytic HSV in children are examined, and we highlight how these may be overcome through various arming strategies. We review the preclinical and clinical evidence demonstrating safety of a variety of oncolytic HSVs. In Part II, we focus on the antitumor efficacy of oncolytic HSV in pediatric tumor types, pediatric clinical advances made to date, and future prospects for utilizing HSV in pediatric patients with solid tumors.

  12. Histone deacetylase inhibitors improve the replication of oncolytic herpes simplex virus in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    James J Cody

    Full Text Available New therapies are needed for metastatic breast cancer patients. Oncolytic herpes simplex virus (oHSV is an exciting therapy being developed for use against aggressive tumors and established metastases. Although oHSV have been demonstrated safe in clinical trials, a lack of sufficient potency has slowed the clinical application of this approach. We utilized histone deacetylase (HDAC inhibitors, which have been noted to impair the innate antiviral response and improve gene transcription from viral vectors, to enhance the replication of oHSV in breast cancer cells. A panel of chemically diverse HDAC inhibitors were tested at three different doses (LD50 for their ability to modulate the replication of oHSV in breast cancer cells. Several of the tested HDAC inhibitors enhanced oHSV replication at low multiplicity of infection (MOI following pre-treatment of the metastatic breast cancer cell line MDA-MB-231 and the oHSV-resistant cell line 4T1, but not in the normal breast epithelial cell line MCF10A. Inhibitors of class I HDACs, including pan-selective compounds, were more effective for increasing oHSV replication compared to inhibitors that selectively target class II HDACs. These studies demonstrate that select HDAC inhibitors increase oHSV replication in breast cancer cells and provides support for pre-clinical evaluation of this combination strategy.

  13. VP22 herpes simplex virus protein can transduce proteins into stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gabanyi, I.; Lojudice, F.H.; Kossugue, P.M. [Centro de Terapia Celular e Molecular, Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Rebelato, E. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Demasi, M.A.; Sogayar, M.C. [Centro de Terapia Celular e Molecular, Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-02-01

    The type I herpes simplex virus VP22 tegument protein is abundant and well known for its ability to translocate proteins from one cell to the other. In spite of some reports questioning its ability to translocate proteins by attributing the results observed to fixation artifacts or simple attachment to the cell membrane, VP22 has been used to deliver several proteins into different cell types, triggering the expected cell response. However, the question of the ability of VP22 to enter stem cells has not been addressed. We investigated whether VP22 could be used as a tool to be applied in stem cell research and differentiation due to its capacity to internalize other proteins without altering the cell genome. We generated a VP22.eGFP construct to evaluate whether VP22 could be internalized and carry another protein with it into two different types of stem cells, namely adult human dental pulp stem cells and mouse embryonic stem cells. We generated a VP22.eGFP fusion protein and demonstrated that, in fact, it enters stem cells. Therefore, this system may be used as a tool to deliver various proteins into stem cells, allowing stem cell research, differentiation and the generation of induced pluripotent stem cells in the absence of genome alterations.

  14. Refractory lymphedema of the hand: an unusual presentation of recurrent herpes simplex virus infection

    Directory of Open Access Journals (Sweden)

    Ali Majdzadeh

    2016-07-01

    Full Text Available Introduction: Herpes Simplex Virus (HSV infection of the hand resulting in lymphatic complications such as lymphangitis and lymphedema is exceedingly uncommon. Although these complications typically resolve in 21 days, they can be persistent and may not resolve even with antiviral use, thereby mimicking dyshidrotic eczema or a bacterial event and often being misdiagnosed and inappropriately treated as such. We report a case of frequently recurring HSV infection of the hand over a long period of time resulting in refractory lymphedema which did not resolve with antiviral treatment. We further endeavor to raise awareness about this highly unusual presentation of HSV infection. A comprehensive review of the literature was conducted for similar cases using PubMed and Medline. Case Report: This is the first reported case with nearly a decade-long interval between the onset of primary HSV infection and the development of chronic lymphedema. Although valacyclovir significantly reduced the episodic aggravation of the lymphedema, it did not entirely resolve it. Similar cases of persistent lymphedema also included a long history of untreated and recurrent HSV infection of the hand, suggesting that this lymphatic outcome may be circumvented by prompt treatment with antivirals. Conclusion: This case report not only presents a highly uncommon lymphatic manifestation and unusual timeline of exacerbation of the very common HSV infection, but also highlights the importance and benefits of early initiation of antiviral therapy and the prevention of reactivation.

  15. Herpes simplex virus detection in oral mucosa lesions in patients undergoing oncologic therapy.

    Science.gov (United States)

    Sepúlveda Tebache, Ester; Brethauer Meier, Ursula; Jiménez Moraga, Marco; Morales Figueroa, Rocío; Rojas Castro, Jaime; Le Fort Canales, Patricia

    2003-01-01

    The presence of Herpes Simplex Virus (HSV) has been a frequent detection in gingivitis and ulcerations of oral mucosa in patients undergoing oncologic therapy. In these patients, lesions tend to show atypical clinical patterns, leading to misdiagnosis. To detect HSV, using an ELISA test, in oral lesions of patients under oncologic therapy, to determine localization of these lesions in the oral cavity, to relate their presence with the general diagnosis of the patient and to compare the test results with the previous clinical diagnosis of the lesions. Thirty lesions where examined in nineteen pediatric patients under oncologic therapy. Direct samples of all lesions were taken and an ELISA test for HSV type I and II was applied to them. General diagnosis of the patients was consigned, as well as localization of the lesions in the oral cavity and clinical diagnosis of them. A database was elaborated with all the information. 33% of lesions were positive to the test, most of them in patients with acute myeloid leukemia. Localization of lesions was not restricted to areas of mucosa attached to periosteum, but also in areas like the dorsum of the tongue. Positive predictivity of clinical diagnosis was 56,25% and negative predictive index was 92,86%. Sensitivity of the test was 90% and specificity was 65%. It is very important to corroborate clinical diagnosis of gingivitis and ulcerative lesions of the oral cavity of patients under oncologic therapy with laboratory tests, because of the atypical clinical presentation that can lead to misdiagnosis.

  16. Herpes Simplex Virus-Type1 (HSV-1) Impairs DNA Repair in Cortical Neurons

    Science.gov (United States)

    De Chiara, Giovanna; Racaniello, Mauro; Mollinari, Cristiana; Marcocci, Maria Elena; Aversa, Giorgia; Cardinale, Alessio; Giovanetti, Anna; Garaci, Enrico; Palamara, Anna Teresa; Merlo, Daniela

    2016-01-01

    Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer’s disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions. PMID:27803664

  17. Antiviral Effects of Blackberry Extract Against Herpes Simplex Virus Type 1

    Science.gov (United States)

    Danaher, Robert J.; Wang, Chunmei; Dai, Jin; Mumper, Russell J.; Miller, Craig S.

    2011-01-01

    Objective To evaluate antiviral properties of blackberry extract against herpes simplex virus type 1 (HSV-1) in vitro. Methods HSV-infected oral epithelial (OKF6) cells and cell-free virus suspensions were treated with blackberry extract (2.24 to 1400 μg/mL) and virus yield and infectivity were quantified by direct plaque assay. Results Blackberry extract ≥ 56 μg/ml inhibited HSV-1 replication in oral epithelial cells by > 99% (p < 0.005). Concentrations ≥ 280 μg/ml were antiviral when the extract was added after virus adsorption and entry. Exposure of cell-free virus to ≥ 280 μg/ml blackberry extract for 15 minutes at room temperature was virucidal (p = 0.0002). The virucidal effects were not due to pH changes at concentrations up to 1500 μg/ml. Conclusions Blackberry extract inhibited the early stages of HSV-1 replication and had potent virucidal activity. These properties suggest that this natural fruit extract could provide advantage as a topical prophylactic/therapeutic agent for HSV infections. PMID:21827957

  18. Modulation of the Intratumoral Immune Landscape by Oncolytic Herpes Simplex Virus Virotherapy

    Directory of Open Access Journals (Sweden)

    Jie Yin

    2017-06-01

    Full Text Available Vaccines and immunotherapeutic approaches to cancers with the advent of immune checkpoint inhibitors and chimeric antigen receptor-modified T cells have recently demonstrated preclinical success and entered clinical trials. Despite advances in these approaches and combinatorial therapeutic regimens, depending on the nature of the cancer and the immune and metabolic landscape within the tumor microenvironment, current immunotherapeutic modalities remain inadequate. Recent clinical trials have demonstrated clear evidence of significant, and sometimes dramatic, antitumor activity, and long-term survival effects of a variety of oncolytic viruses (OVs, particularly oncolytic herpes simplex virus (oHSV. Acting as a multifaceted gene therapy vector and potential adjuvant-like regimens, oHSV can carry genes encoding immunostimulatory molecules in its genome. The oncolytic effect of oHSV and the inflammatory response that the virus stimulates provide a one-two punch at attacking tumors. However, mechanisms underlying oHSV-induced restoration of intratumoral immunosuppression demand extensive research in order to further improve its therapeutic efficacy. In this review, we discuss the current OV-based therapy, with a focus on the unique aspects of oHSV-initiated antiviral and antitumor immune responses, arising from virus-mediated immunological cell death to intratumoral innate and adaptive immunity.

  19. Knockdown of DNA ligase IV/XRCC4 by RNA interference inhibits herpes simplex virus type I DNA replication.

    Science.gov (United States)

    Muylaert, Isabella; Elias, Per

    2007-04-13

    Herpes simplex virus has a linear double-stranded DNA genome with directly repeated terminal sequences needed for cleavage and packaging of replicated DNA. In infected cells, linear genomes rapidly become endless. It is currently a matter of discussion whether the endless genomes are circles supporting rolling circle replication or arise by recombination of linear genomes forming concatemers. Here, we have examined the role of mammalian DNA ligases in the herpes simplex virus, type I (HSV-1) life cycle by employing RNA interference (RNAi) in human 1BR.3.N fibroblasts. We find that RNAi-mediated knockdown of DNA ligase IV and its co-factor XRCC4 causes a hundred-fold reduction of virus yield, a small plaque phenotype, and reduced DNA synthesis. The effect is specific because RNAi against DNA ligase I or DNA ligase III fail to reduce HSV-1 replication. Furthermore, RNAi against DNA ligase IV and XRCC4 does not affect replication of adenovirus. In addition, high multiplicity infections of HSV-1 in human DNA ligase IV-deficient cells reveal a pronounced delay of production of infectious virus. Finally, we demonstrate that formation of endless genomes is inhibited by RNAi-mediated depletion of DNA ligase IV and XRCC4. Our results suggests that DNA ligase IV/XRCC4 serves an important role in the replication cycle of herpes viruses and is likely to be required for the formation of the endless genomes early during productive infection.

  20. Apresentação atípica de infecção por herpes simples em um paciente imunossuprimido Atypical presentation of herpes simplex infection in a immunosupressed patient

    Directory of Open Access Journals (Sweden)

    Maira Mitsue Mukai

    2005-04-01

    Full Text Available A infecção pelo vírus do herpes simples leva a um quadro clínico peculiar de fácil reconhecimento pelo médico. No entanto, em indivíduos imunossuprimidos, a apresentação clínica pode ser atípica, dificultando o diagnóstico e o tratamento. Em virtude disso, apresenta-se um caso de herpes simples ocorrendo em paciente submetido à quimioterapia.The herpes simplex infection can produce peculiar clinical features easily recognized by the physician. However, in immunocompromised people, the clinical presentation can be atypical, difficulting the diagnosis and treatment. Therefore, a case of herpes simplex occurring in a pacient taking chemotherapy is presented.

  1. A proprietary topical preparation containing EGCG-stearate and glycerin with inhibitory effects on herpes simplex virus: case study.

    Science.gov (United States)

    Zhao, Man; Jiang, Jinyan; Zheng, Rongrong; Pearl, Henna; Dickinson, Douglas; Fu, Baiping; Hsu, Stephen

    2012-10-01

    The effects of a proprietary topical formulation containing EGCG-stearate in 100% glycerin USP were studied in two volunteer patients with recurrent herpes simplex (HSV) type 1. Application during early onset (prodromal stage) in a patient with herpes labialis prevented lesion progression. In a second patient with herpetic stomatitis, application of the formula during a later stage (inflammation stage) led to a remarkably shortened duration of symptoms. In contrast, a third patient provided 100% glycerin USP only as placebo failed to demonstrate any therapeutic or preventive effect against lesion occurrence or duration of lesion and healing time. These results suggest that this proprietary topical preparation could be used effectively to prevent and treat HSV-induced symptoms, and warrants further clinical investigation.

  2. Pathogenic microbial flora of genital ulcers in Sheffield with particular reference to herpes simplex virus and Haemophilus ducreyi.

    Science.gov (United States)

    Kinghorn, G R; Hafiz, S; McEntegart, M G

    1982-12-01

    The pathogenic microbial flora of genital ulcers in 161 (80 men and 81 women) unselected patients was studied prospectively. In only one case was Treponema pallidum responsible whereas herpes simplex virus was considered to be the cause of 130 (80.8%) genital ulcers. H ducreyi was isolated from 46 (28.6%) patients, most commonly as a secondary pathogen in herpetic lesions. Two or more pathogens were isolated from the ulcers in 67 (41.6%) patients, and in 21 (13%) patients no pathogens were isolated. Our results indicate an urgent need for antiviral treatment to reduce the local reservoir of genital herpes, challenge traditional concepts about the prevalence of H ducreyi in Britain, and call for a reappraisal of its role in the causation of genital ulcers.

  3. [Using the preparation "human immunoglobulin against herpes simplex virus type 1 for intramuscular injections" in the complex therapy of nervous system diseases].

    Science.gov (United States)

    Rudenko, A O; Diachenko, N S; Nesterova, N V; Kurishchuk, K V; Berestova, T H; Zahorodnia, S D; Riads'ka, L S; Muravs'ka, L V; Andrieieva, O H; Baranova, H V

    2004-01-01

    The technology of obtaining of specific immunoglobulin for serotherapy of neuroinfection caused by virus herpes simplex 1 type was developed. The patients presented with the following diseases: arachnoencephalitis, encephalopolyradiculoneuritis, encephalomyelitis, encephalitis, arachnoiditis, polyneuropathy, encephalomyelopolyradiculoneuritis, meningoencephalitis. The study showed good tolerance and safety of the medicine, no adverse effects registered during the study. The assessed median score of the efficacy was 2.8 from 3. The obtained results suggest using the liquid form preparation for intramuscular injection "Immunoglobulin for treatment of neuroinfection caused by virus herpes simplex type 1". The Close corporation "Biofarma" located in Kyiv produces this medicine.

  4. Apple pomace, a by-product from the asturian cider industry, inhibits herpes simplex virus types 1 and 2 in vitro replication: study of its mechanisms of action.

    Science.gov (United States)

    Alvarez, Angel L; Melón, Santiago; Dalton, Kevin P; Nicieza, Inés; Roque, Annele; Suárez, Belén; Parra, Francisco

    2012-06-01

    The anti-herpes simplex virus type 1 and anti-herpes simplex virus type 2 effects of apple pomace, a by-product from the cider-processing industry, were investigated. The mechanisms of antiviral action were assessed using a battery of experiments targeting sequential steps in the viral replication cycle. The anti-herpetic mechanisms of apple pomaces included the inhibition of virus attachment to the cell surface and the arrest of virus entry and uncoating. Quercitrin and procyanidin B2 were found to play a crucial role in the antiviral activity.

  5. Apple Pomace, a By-Product from the Asturian Cider Industry, Inhibits Herpes Simplex Virus Types 1 and 2 In Vitro Replication: Study of Its Mechanisms of Action

    Science.gov (United States)

    Melón, Santiago; Dalton, Kevin P.; Nicieza, Inés; Roque, Annele; Suárez, Belén; Parra, Francisco

    2012-01-01

    Abstract The anti–herpes simplex virus type 1 and anti–herpes simplex virus type 2 effects of apple pomace, a by-product from the cider-processing industry, were investigated. The mechanisms of antiviral action were assessed using a battery of experiments targeting sequential steps in the viral replication cycle. The anti-herpetic mechanisms of apple pomaces included the inhibition of virus attachment to the cell surface and the arrest of virus entry and uncoating. Quercitrin and procyanidin B2 were found to play a crucial role in the antiviral activity. PMID:22424460

  6. Seroprevalencia de la infección por el virus herpes simplex tipo 2 en tres grupos poblacionales de la Ciudad de México Herpes simplex virus type 2 seroprevalence among three female population groups from Mexico City

    Directory of Open Access Journals (Sweden)

    Carlos J Conde-González

    2003-01-01

    Full Text Available OBJETIVO: Determinar la seroprevalencia de infección por el virus herpes simplex tipo 2 y los factores epidemiológicos asociados a ella, en tres grupos de población femenina de la Ciudad de México. MATERIAL Y MÉTODOS: Estudio transversal efectuado en el año 2000, que incluyó mujeres de la Ciudad de México diagnosticadas con cáncer de mama, cáncer cervical , y mujeres de población general negativas al Papanicolaou. Todas las participantes proporcionaron su consentimiento informado para responder un cuestionario sociodemográfico y de vida sexual, y permitir la toma de una muestra sanguínea. La presencia de anticuerpos contra el virus herpes simplex tipo 2 entre las mujeres se realizó por la técnica de "Western blot"específica para el virus herpes simplex tipo 2; las asociaciones entre estos resultados y los datos de la encuesta se analizaron estadísticamente, de manera cruda y ajustada. RESULTADOS: Las mujeres concáncer cervical tuvieron una seroprevalencia de infección por el virus herpes simplex tipo 2 de 46.8% (191/408; las de población general negativas al Papanicolaou de 29.3% (214/730, y aquellas con cáncer de mama de 22.6% (29/128. Las variables asociadas significativamente a la seropositividad contra este virus fueron la edad creciente, el aumento en el número de parejas sexuales, tener cáncer cervical, y entre las mujeres con esa patología, el inicio antes de los 21 años de edad de la actividad sexual y el estar divorciadas o separadas. CONCLUSIONES: Los hallazgos observados revelaron diferencias estadísticas en la seroprevalencia del virus herpes, de acuerdo con los grupos poblacionales estudiados. La frecuencia global de la infección viral entre las participantes las sitúa en un riesgo intermedio, en comparación con otros grupos poblacionales que en México son de alto y bajo riesgo (trabajadoras sexuales y estudiantes universitarias, respectivamente, analizados en años recientes. Las principales caracter

  7. Clinical Efficacy of Oral Ganciclovir for Prophylaxis and Treatment of Recurrent Herpes Simplex Keratitis

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2015-01-01

    Full Text Available Background: Herpes simplex keratitis (HSK caused by herpes simplex virus 1 (HSV-1, which has high recurrent rate and incidence of severe vision loss, is the leading cause of infectious blindness in the world. The aim was to explore the clinical efficacy of oral ganciclovir (GCV in the prevention of recurrent HSK. Methods: A multicenter, prospective, randomized, single-blind, and controlled clinical trial was conducted from April 2010 to June 2013. One hundred seventy-three patients (173 eyes involved who were diagnosed as recurrent HSK definitely, including stromal keratitis and corneal endotheliitis, were divided into three groups randomly: negative control (placebo group was topically administered with 0.15% GCV ophthalmic gel, 4 times per day and 0.1% fluorometholone eye drops, 3 times per day until resolution of HSK; positive control acyclovir (ACV group was topically adopted the same ophthalmic gel and eye drops and additionally received oral ACV 400 mg 5 times a day for 10 weeks and followed by 400 mg 2 times per day for 6 months; test GCV group was topically adopted the same treatment as negative control group and additionally received oral GCV 1000 mg 3 times per day for 8 weeks. The symptoms and signs were evaluated before and after the therapy 1 st week, 2 nd week and then followed up every 2 weeks until recovery. Furthermore, we followed up recurrence of HSK for every 3 months after recovery and then assessed the cure time, recurrent rate and adverse reactions. Results: One hundred and seventy-three patients were followed up 7-48 months (mean 32.1 ± 12.3 months, but 34 patients were failed to follow-up. The cure time was 12.1 ± 4.3, 11.9 ± 4.0 weeks in negative control (placebo group and positive control ACV group respectively (P = 0.991, which was longer than that in test GCV group (8.6 ± 2.8 weeks and there was a significant difference between test GCV group and negative control (placebo group or positive control ACV group (P

  8. The morphogenesis of herpes simplex virus type 1 in infected parental mouse L fibroblasts and mutant gro29 cells

    DEFF Research Database (Denmark)

    Jensen, Helle Lone; Norrild, Bodil

    2003-01-01

    Mutants of cell lines and viruses are important biological tools. The pathway of herpesvirus particle maturation and egress are contentious issues. The mutant gro29 line of mouse L cells is defective for egress of herpes simplex virus type 1 (HSV-1) virions, and a candidate for studies of virus......-cell interactions. The properties of uninfected and HSV-1-infected L fibroblasts and gro29 cells investigated by protein assay, immunoblot, titration assay, immunofluorescence light microscopy and immunogold cryosection electron microscopy are reported. The ultrastructure of both HSV-1-infected L and gro29 cells...

  9. [Follow-up serological study of herpes simplex and cytomegalovirus in Cuban patients infected with human immunodeficiency virus (HIV)].

    Science.gov (United States)

    Resik, S; Santana, E; Rivero, J; Pérez, A B; Kourí, V; Larralde, O

    1997-01-01

    The evolution serological response against the herpes simplex virus and citomegalovirus in HIV infected patients grouped into different stages of the disease was studied. Fluctuations in the TPG of antibodies were observed in these values in a cyclical way through time. There was a greater significant difference among the TPG of antibodies against HSV in the group of asymptomatic patients compared with AIDS patients and with those who died. There is a marked decrease in the TPG of antibodies against HSV and CMV approximately one year before the death of patients.

  10. Cervicovaginal Neutralizing Antibodies to Herpes Simplex Virus (HSV) in Women Seropositive for HSV Types 1 and 2

    OpenAIRE

    Mbopi-Kéou, Francois-Xavier; Bélec, Laurent; Dalessio, Julie; Legoff, Jérôme; Grésenguet, Gérard; Mayaud, Philippe; Brown, David W.G.; Ashley Morrow, Rhoda

    2003-01-01

    Antibodies to herpes simplex virus type 1 (HSV-1) and HSV-2 of the immunoglobulin G (IgG) and IgA isotypes were detected in the cervicovaginal secretions (CVS) of 77 HSV-1- and HSV-2-seropositive but clinically asymptomatic African women by type-specific enhanced chemiluminescence Western blotting (ECL-WB). Of the 77 subjects, 34 were HIV negative, shedding HSV-2 DNA in their genital secretions; 20 were HIV positive, shedding HSV-2 DNA; and 23 were HIV negative, not shedding HSV-2 DNA. HSV-sp...

  11. Rapid detection of herpes simplex virus in clinical samples by flow cytometry after amplification in tissue culture.

    OpenAIRE

    McSharry, J J; Costantino, R; McSharry, M B; Venezia, R A; Lehman, J M

    1990-01-01

    Murine monoclonal antibodies (MAbs) against herpes simplex virus type 1 and 2 (HSV-1 and -2, respectively) nuclear antigens were used to identify cells infected with HSV-1 or -2 by indirect immunofluorescence in conjunction with flow cytometry after virus amplification of MRC-5 cell monolayers. The results indicate that MAbs Q1, Q2, and H-640 detect HSV-1- and HSV-2-infected cells, MAb SD-1 detects HSV-2- but not HSV-1-infected cells, and MAb 58-S detects HSV-1- but not HSV-2-infected cells. ...

  12. Comparison of Herpes simplex virus plaque development after viral treatment with anti-DNA or antilipid agents

    Energy Technology Data Exchange (ETDEWEB)

    Coohill, T.P.; Babich, M.; Taylor, W.D.; Snipes, W.

    1980-06-01

    The plaque development of Herpes simplex virus type 1 (HSV) is slower for viruses treated with two anti-DNA agents: ultraviolet radiation (uv) or n-acetoxy-2-acetyl-aminofluorene. For HSV treated with three antimembrane agents - butylated hydroxytoluene, acridine plus near uv radiation, or ether - the plaque development time is the same as for untreated viruses. These differences hold even for viruses that survived treatment that lowered viability below the 1% level. Gamma ray inactivation of HSV produces no change in plaque development even though this agent is believed to preferentially affect viral DNA.

  13. Role of a cdk5-associated protein, p35, in herpes simplex virus type 1 replication in vivo

    OpenAIRE

    2010-01-01

    Previous studies have shown that herpes simplex virus type 1 (HSV-1) replication is inhibited by the cyclin-dependent kinase (cdk) inhibitor roscovitine. One roscovitine-sensitive cdk that functions in neurons is cdk5, which is activated in part by its binding partner, p35. Because HSV establishes latent infections in sensory neurons, we sought to determine the role p35 plays in HSV-1 replication in vivo. For these studies, wild-type (wt) and p35-/- mice were infected with HSV-1 using the mou...

  14. Residues of the UL25 Protein of Herpes Simplex Virus That Are Required for Its Stable Interaction with Capsids ▿

    OpenAIRE

    Cockrell, Shelley K.; Huffman, Jamie B.; Toropova, Katerina; James F Conway; Homa, Fred L.

    2011-01-01

    The herpes simplex virus 1 (HSV-1) UL25 gene product is a minor capsid component that is required for encapsidation, but not cleavage, of replicated viral DNA. UL25 is located on the capsid surface in a proposed heterodimer with UL17, where five copies of the heterodimer are found at each of the capsid vertices. Previously, we demonstrated that amino acids 1 to 50 of UL25 are essential for its stable interaction with capsids. To further define the UL25 capsid binding domain, we generated reco...

  15. Detection of Treponema pallidum, Herpes Simplex Virus, and Haemophilus ducreyi from Genital Ulcers by Multiplex Polymerase Chain Reaction

    Institute of Scientific and Technical Information of China (English)

    周华; 傅笑冰; 熊礼宽; 杨帆; 洪福昌; 曾序春; 董时富

    2001-01-01

    Objective: To evaluate the clinical application of multiplex PCR in the detection of Treponema pallidum, Herpes simplex virus (HSV), and Haemophilus ducreyi. Method: Three standard strains were used to set up a multiplex PCR (MPCR) for detecting syphilis, herpes genitalis, and chancroid simultaneously. Samples from 122 patients with genital ulcer disease(GUD) were subjected to MPCR and the results were compared with these of dark-fidd microscopy and TP serology, HSV anligen ELISA,and H. ducreyi culture, Result: In the 122 patients with GUD, MPCR identified 34 casesof T.pallidum infection, 40 cases of HSV infection, and 2 cases of mixed infection of T.pallidum and herpes. No positive results of H. ducreyi were found. The sensitivity of MPCR to T. pallidum and herpes was 100% and 93.3%, respectivdy. The sensitivities of dark-field microscopy and TP serology, HSV antigen ELISA, and H. ducreyi culture was 35.3%, 50% and 100%, respectively. Conclusion: MPCR showed a relatively higher sensitivity for T.pallidum as compared with the routine techniques. Although its sensitivity for HSV was not as good as that of antigen ELISA, it also yielde da high detection rate. MPCR can detect more than one pathogen. It is simple, quick, sensitive, and suitable for clinical use or epidemiological investigation.

  16. Functional Interaction between Class II Histone Deacetylases and ICP0 of Herpes Simplex Virus Type 1

    Science.gov (United States)

    Lomonte, Patrick; Thomas, Joëlle; Texier, Pascale; Caron, Cécile; Khochbin, Saadi; Epstein, Alberto L.

    2004-01-01

    This study describes the physical and functional interactions between ICP0 of herpes simplex virus type 1 and class II histone deacetylases (HDACs) 4, 5, and 7. Class II HDACs are mainly known for their participation in the control of cell differentiation through the regulation of the activity of the transcription factor MEF2 (myocyte enhancer factor 2), implicated in muscle development and neuronal survival. Immunofluorescence experiments performed on transfected cells showed that ICP0 colocalizes with and reorganizes the nuclear distribution of ectopically expressed class I and II HDACs. In addition, endogenous HDAC4 and at least one of its binding partners, the corepressor protein SMRT (for silencing mediator of retinoid and thyroid receptor), undergo changes in their nuclear distribution in ICP0-transfected cells. As a result, during infection endogenous HDAC4 colocalizes with ICP0. Coimmunoprecipitation and glutathione S-transferase pull-down assays confirmed that class II but not class I HDACs specifically interacted with ICP0 through their amino-terminal regions. This region, which is not conserved in class I HDACs but homologous to the MITR (MEF2-interacting transcription repressor) protein, is responsible for the repression, in a deacetylase-independent manner, of MEF2 by sequestering it under an inactive form in the nucleus. Consequently, we show that ICP0 is able to overcome the HDAC5 amino-terminal- and MITR-induced MEF2A repression in gene reporter assays. This is the first report of a viral protein interacting with and controlling the repressor activity of class II HDACs. We discuss the putative consequences of such an interaction for the biology of the virus both during lytic infection and reactivation from latency. PMID:15194749

  17. Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.

    Science.gov (United States)

    Harris, Steven A; Harris, Elizabeth A

    2015-01-01

    This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer's disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-β (Aβ) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of Aβ damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials.

  18. Characterization of a major late herpes simplex virus type 1 mRNA.

    Science.gov (United States)

    Costa, R H; Devi, B G; Anderson, K P; Gaylord, B H; Wagner, E K

    1981-05-01

    A major, late 6-kilobase (6-kb) mRNa mapping in the large unique region of herpes simplex virus type 1 (HSV-1) was characterized by using two recombinant DNA clones, one containing EcoRI fragment G (0.190 to 0.30 map units) in lambda. WES.B (L. Enquist, M. Madden, P. Schiop-Stansly, and G. Vandl Woude, Science 203:541-544, 1979) and one containing HindIII fragment J (0.181 to 0.259 map units) in pBR322. This 6-kb mRNA had its 3' end to the left of 0.231 on the prototypical arrangement of the HSV-1 genome and was transcribed from right to left. It was bounded on both sides by regions containing a large number of distinct mRNA species, and its 3' end was partially colinear with a 1.5-kb mRNA which encoded a 35,000-dalton polypeptide. The 6-kb mRNA encoded a 155,000-dalton polypeptide which was shown to be the only one of this size detectable by hybrid-arrested translation encoded by late polyadenylated polyribosomal RNA. The S1 nuclease mapping experiments indicated that there were no introns in the coding sequence for this mRNA and that its 3' end mapped approximately 800 nucleotides to the left of the BglII site at 0.231, whereas its 5' end extended very close to the BamHI site at 0.266.

  19. Herpes simplex virus type 2, genital ulcers and HIV-1 disease progression in postpartum women.

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    Alison C Roxby

    Full Text Available BACKGROUND: Co-infection with herpes simplex virus type 2 (HSV-2 has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear. METHODS: HIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12-24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI, and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression. RESULTS: Among 296 women, 254 (86% were HSV-2-seropositive. Only 30 (10% women had prior or current genital ulcer disease (GUD; median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR 2.79, 95% CI: 1.33-5.85, and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93-15.83. Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07. CONCLUSIONS: HSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2.

  20. Herpes simplex virus lower respiratory tract infection in patients with solid tumors.

    Science.gov (United States)

    Aisenberg, Gabriel M; Aisenberg, Galbiel; Torres, Harrys A; Torres, Harrys; Tarrand, Jeffrey; Safdar, Amar; Bodey, Gerald; Chemaly, Roy F

    2009-01-01

    The clinical significance of herpes simplex virus (HSV) isolated in lower respiratory tract specimens (LRTS) of patients with solid tumors (ST) is unknown. In the current study, the authors attempted to determine the clinical relevance of this finding among ST patients. The authors reviewed records of ST patients admitted to the study institution between April 2000 and April 2004 with clinical and radiologic evidence of pneumonia, and HSV identified in LRTS by culture alone or culture and cytology. Patients were categorized as having proven (HSV identified by culture and cytology from the LRTS), probable (HSV as the sole pathogen by culture alone), and possible (HSV along with copathogens identified by culture) HSV pneumonia. Forty-five ST patients with either proven (6 patients), probable (25 patients), or possible (14 patients) HSV pneumonia were identified. When compared with patients with probable or possible HSV pneumonia, more patients with proven infection were on mechanical ventilation (40% vs 50% vs 100%, respectively; P=.03), and had longer length of stay in the intensive care unit (12 days vs 13 days vs 26 days, respectively; P=.05). The overall mortality rate was 22% (10 patients). Four of 25 (16%) patients who received HSV-directed antiviral therapy died during their hospital stay versus 6 of 20 (30%) who were not treated (P=.3). None of the 6 patients with proven HSV pneumonia who were treated with acyclovir died. On univariate analysis, risk factors for mortality included underlying breast cancer, an Acute Physiology and Chronic Health Evaluation (APACHE) II score>15, admission to the intensive care unit, and use of mechanical ventilation and vasopressors (all P15 being found to be independent predictors of death by multiple logistic regression analysis (all P

  1. Targeting Holliday junctions by origin DNA-binding protein of herpes simplex virus type 1.

    Science.gov (United States)

    Moiseeva, E D; Bazhulina, N P; Gursky, Y G; Grokhovsky, S L; Surovaya, A N; Gursky, G V

    2017-03-01

    In the present paper, the interactions of the origin binding protein (OBP) of herpes simplex virus type 1 (HSV1) with synthetic four-way Holliday junctions (HJs) were studied using electrophoresis mobility shift assay and the FRET method and compared with the interactions of the protein with duplex and single-stranded DNAs. It has been found that OBP exhibits a strong preference for binding to four-way and three-way DNA junctions and possesses much lower affinities to duplex and single-stranded DNAs. The protein forms three types of complexes with HJs. It forms complexes I and II which are reminiscent of the tetramer and octamer complexes with four-way junction of HJ-specific protein RuvA of Escherichia coli. The binding approaches saturation level when two OBP dimers are bound per junction. In the presence of Mg(2+) ions (≥2 mM) OBP also interacts with HJ in the stacked arm form (complex III). In the presence of 5 mM ATP and 10 mM Mg(2+) ions OBP catalyzes processing of the HJ in which one of the annealed oligonucleotides has a 3'-terminal tail containing 20 unpaired thymine residues. The observed preference of OBP for binding to the four-way DNA junctions provides a basis for suggestion that OBP induces large DNA structural changes upon binding to Box I and Box II sites in OriS. These changes involve the bending and partial melting of the DNA at A+T-rich spacer and also include the formation of HJ containing Box I and Box II inverted repeats and flanking DNA sequences.

  2. Evidence for translational regulation by the herpes simplex virus virion host shutoff protein.

    Science.gov (United States)

    Saffran, Holly A; Read, G Sullivan; Smiley, James R

    2010-06-01

    The herpes simplex virus (HSV) virion host shutoff protein (vhs) encoded by gene UL41 is an mRNA-specific RNase that triggers accelerated degradation of host and viral mRNAs in infected cells. We report here that vhs is also able to modulate reporter gene expression without greatly altering the levels of the target mRNA in transient-transfection assays conducted in HeLa cells. We monitored the effects of vhs on a panel of bicistronic reporter constructs bearing a variety of internal ribosome entry sites (IRESs) located between two test cistrons. As expected, vhs inhibited the expression of the 5' cistrons of all of these constructs; however, the response of the 3' cistron varied with the IRES: expression driven from the wild-type EMCV IRES was strongly suppressed, while expression controlled by a mutant EMCV IRES and the cellular ApaF1, BiP, and DAP5 IRES elements was strongly activated. In addition, several HSV type 1 (HSV-1) 5' untranslated region (5' UTR) sequences also served as positive vhs response elements in this assay. IRES activation was also observed in 293 and HepG2 cells, but no such response was observed in Vero cells. Mutational analysis has yet to uncouple the ability of vhs to activate 3' cistron expression from its shutoff activity. Remarkably, repression of 5' cistron expression could be observed under conditions where the levels of the reporter RNA were not correspondingly reduced. These data provide strong evidence that vhs can modulate gene expression at the level of translation and that it is able to activate cap-independent translation through specific cis-acting elements.

  3. Herpes simplex virus virion host shutoff (vhs) activity alters periocular disease in mice.

    Science.gov (United States)

    Smith, T J; Ackland-Berglund, C E; Leib, D A

    2000-04-01

    During lytic infection, the virion host shutoff (vhs) protein of herpes simplex virus (HSV) mediates the rapid degradation of RNA and shutoff of host protein synthesis. In mice, HSV type 1 (HSV-1) mutants lacking vhs activity are profoundly attenuated. HSV-2 has significantly higher vhs activity than HSV-1, eliciting a faster and more complete shutoff. To examine further the role of vhs activity in pathogenesis, we generated an intertypic recombinant virus (KOSV2) in which the vhs open reading frame of HSV-1 strain KOS was replaced with that of HSV-2 strain 333. KOSV2 and a marker-rescued virus, KOSV2R, were characterized in cell culture and tested in an in vivo mouse eye model of latency and pathogenesis. The RNA degradation kinetics of KOSV2 was identical to that of HSV-2 333, and both showed vhs activity significantly higher than that of KOS. This demonstrated that the fast vhs-mediated degradation phenotype of 333 had been conferred upon KOS. The growth of KOSV2 was comparable to that of KOS, 333, and KOSV2R in cell culture, murine corneas, and trigeminal ganglia and had a reactivation frequency similar to those of KOS and KOSV2R from explanted latently infected trigeminal ganglia. There was, however, significantly reduced blepharitis and viral replication within the periocular skin of KOSV2-infected mice compared to mice infected with either KOS or KOSV2R. Taken together, these data demonstrate that heightened vhs activity, in the context of HSV-1 infection, leads to increased viral clearance from the skin of mice and that the replication of virus in the skin is a determining factor for blepharitis. These data also suggest a role for vhs in modulating host responses to HSV infection.

  4. Pathogenesis of herpes simplex virus type 2 virion host shutoff (vhs) mutants.

    Science.gov (United States)

    Smith, Tracy J; Morrison, Lynda A; Leib, David A

    2002-03-01

    During lytic infection, the virion host shutoff (vhs) protein mediates the rapid degradation of mRNA and the shutoff of host protein synthesis. In vivo, herpes simplex virus type 1 (HSV-1) mutants lacking vhs activity are profoundly attenuated. Homologs of vhs exist in all of the neurotropic herpesviruses, and the goal of this study was to determine the virulence of HSV-2 mutants lacking vhs. Two HSV-2 recombinants were used in this study: 333-vhsB, which has a lacZ cassette inserted into the N terminus of vhs, and 333d41, which has a 939-bp deletion in vhs. As expected, both 333-vhsB and 333d41 failed to induce the cellular RNA degradation characteristic of HSV. Corneal, vaginal, and intracerebral routes of infection were used to study pathogenesis. Both viruses grew to significantly lower titers in the corneas, trigeminal ganglia, vaginas, dorsal root ganglia, spinal cords, and brains of mice than wild-type and rescue viruses, with a correspondingly reduced induction of disease. Both viruses, however, reactivated efficiently from explanted trigeminal ganglia, showing that vhs is dispensable for reactivation. The lethality of 333d41 following peripheral infection of mice, however, was significantly higher than that of 333-vhsB, suggesting that some of the attenuation of 333-vhsB may be due to the presence of a lacZ cassette in the vhs locus. Taken together, these data show that vhs represents an important determinant of HSV-2 pathogenesis and have implications for the design of HSV-2 recombinants and vaccines.

  5. An investigative peptide-acyclovir combination to control herpes simplex virus type 1 ocular infection.

    Science.gov (United States)

    Park, Paul J; Antoine, Thessicar E; Farooq, Asim V; Valyi-Nagy, Tibor; Shukla, Deepak

    2013-09-27

    To investigate the efficacy of a combination treatment composed of the cationic, membrane-penetrating peptide G2, and acyclovir (ACV) in both in vitro and ex vivo models of herpes simplex virus 1 (HSV-1) ocular infection. The antiviral activity of a combined G2 peptide and ACV therapy (G2-ACV) was assessed in various treatment models. Viral entry, spread, and plaque assays were performed in vitro to assess the prophylactic efficacy of G2, G2-ACV, and ACV treatments. In the ex vivo model of HSV-1 infection, the level of viral inhibition was also compared among the three treatment groups via Western blot analysis and immunohistochemistry. The potential change in expression of the target receptor for G2 was also assessed using immunohistochemistry and RT-PCR. Statistically significant effects against HSV-1 infection were seen in all treatment groups in the viral entry, spread, and plaque assays. The greatest effects against HSV-1 infection in vitro were seen in the G2-ACV group. In the ex vivo model, statistically significant anti-HSV-1 effects were also noted in all control groups. At 24 hours, the greatest inhibitory effect against HSV-1 infection was seen in the ACV group. At 48 hours, however, the G2-ACV-treated group demonstrated the greatest antiviral activity. Syndecan-1, a target of G2, was found to be upregulated at 12-hours postinfection. This study shows that G2-ACV may be an effective antiviral against HSV-1 (KOS) strain when applied as single prophylactic applications with or without continuous doses postinfection.

  6. An Investigative Peptide–Acyclovir Combination to Control Herpes Simplex Virus Type 1 Ocular Infection

    Science.gov (United States)

    Park, Paul J.; Antoine, Thessicar E.; Farooq, Asim V.; Valyi-Nagy, Tibor; Shukla, Deepak

    2013-01-01

    Purpose. To investigate the efficacy of a combination treatment composed of the cationic, membrane-penetrating peptide G2, and acyclovir (ACV) in both in vitro and ex vivo models of herpes simplex virus 1 (HSV-1) ocular infection. Methods. The antiviral activity of a combined G2 peptide and ACV therapy (G2-ACV) was assessed in various treatment models. Viral entry, spread, and plaque assays were performed in vitro to assess the prophylactic efficacy of G2, G2-ACV, and ACV treatments. In the ex vivo model of HSV-1 infection, the level of viral inhibition was also compared among the three treatment groups via Western blot analysis and immunohistochemistry. The potential change in expression of the target receptor for G2 was also assessed using immunohistochemistry and RT-PCR. Results. Statistically significant effects against HSV-1 infection were seen in all treatment groups in the viral entry, spread, and plaque assays. The greatest effects against HSV-1 infection in vitro were seen in the G2-ACV group. In the ex vivo model, statistically significant anti–HSV-1 effects were also noted in all control groups. At 24 hours, the greatest inhibitory effect against HSV-1 infection was seen in the ACV group. At 48 hours, however, the G2-ACV–treated group demonstrated the greatest antiviral activity. Syndecan-1, a target of G2, was found to be upregulated at 12-hours postinfection. Conclusions. This study shows that G2-ACV may be an effective antiviral against HSV-1 (KOS) strain when applied as single prophylactic applications with or without continuous doses postinfection. PMID:23989188

  7. Silencing Status Epilepticus-Induced BDNF Expression with Herpes Simplex Virus Type-1 Based Amplicon Vectors.

    Directory of Open Access Journals (Sweden)

    Chiara Falcicchia

    Full Text Available Brain-derived neurotrophic factor (BDNF has been found to produce pro- but also anti-epileptic effects. Thus, its validity as a therapeutic target must be verified using advanced tools designed to block or to enhance its signal. The aim of this study was to develop tools to silence the BDNF signal. We generated Herpes simplex virus type 1 (HSV-1 derived amplicon vectors, i.e. viral particles containing a genome of 152 kb constituted of concatameric repetitions of an expression cassette, enabling the expression of the gene of interest in multiple copies. HSV-1 based amplicon vectors are non-pathogenic and have been successfully employed in the past for gene delivery into the brain of living animals. Therefore, amplicon vectors should represent a logical choice for expressing a silencing cassette, which, in multiple copies, is expected to lead to an efficient knock-down of the target gene expression. Here, we employed two amplicon-based BDNF silencing strategies. The first, antisense, has been chosen to target and degrade the cytoplasmic mRNA pool of BDNF, whereas the second, based on the convergent transcription technology, has been chosen to repress transcription at the BDNF gene. Both these amplicon vectors proved to be effective in down-regulating BDNF expression in vitro, in BDNF-expressing mesoangioblast cells. However, only the antisense strategy was effective in vivo, after inoculation in the hippocampus in a model of status epilepticus in which BDNF mRNA levels are strongly increased. Interestingly, the knocking down of BDNF levels induced with BDNF-antisense was sufficient to produce significant behavioral effects, in spite of the fact that it was produced only in a part of a single hippocampus. In conclusion, this study demonstrates a reliable effect of amplicon vectors in knocking down gene expression in vitro and in vivo. Therefore, this approach may find broad applications in neurobiological studies.

  8. A molecular method for typing Herpes simplex virus isolates as an alternative to immunofluorescence methods

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    Abraham A

    2009-01-01

    Full Text Available Background: Typing of Herpes simplex virus (HSV isolates is required to identify the virus isolated in culture. The methods available for this include antigen detection by immunofluorescence (IF assays and polymerase chain reaction (PCR. This study was undertaken to standardize a molecular method for typing of HSV and compare it with a commercial IF reagent for typing. Objectives: To compare a molecular method for typing HSV isolates with a monoclonal antibody (MAb based IF test. Study design : This cross-sectional study utilized four reference strains and 42 HSV isolates obtained from patients between September 1998 and September 2004. These were subjected to testing using an MAb-based IF test and a PCR that detects the polymerase ( pol gene of HSV isolates. Results: The observed agreement of the MAb IF assay with the pol PCR was 95.7%. Fifty four point eight percent (23/42 of isolates tested by IF typing were found to be HSV-1, 40.5% (17/42 were HSV-2, and two (4.8% were untypable using the MAb IF assay. The two untypable isolates were found to be HSV-2 using the pol PCR. In addition, the cost per PCR test for typing is estimated to be around Rs 1,300 (USD 30, whereas the cost per MAb IF test is about Rs 1,500 (USD 35 including all overheads (reagents, instruments, personnel time, and consumables. Conclusion: The pol PCR is a cheaper and more easily reproducible method for typing HSV isolates as compared to the IF test. It could replace the IF-based method for routine typing of HSV isolates as availability of PCR machines (thermal cyclers is now more widespread than fluorescence microscopes in a country like India.

  9. ICP0 dismantles microtubule networks in herpes simplex virus-infected cells.

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    Mingyu Liu

    Full Text Available Infected-cell protein 0 (ICP0 is a RING finger E3 ligase that regulates herpes simplex virus (HSV mRNA synthesis, and strongly influences the balance between latency and replication of HSV. For 25 years, the nuclear functions of ICP0 have been the subject of intense scrutiny. To obtain new clues about ICP0's mechanism of action, we constructed HSV-1 viruses that expressed GFP-tagged ICP0. To our surprise, both GFP-tagged and wild-type ICP0 were predominantly observed in the cytoplasm of HSV-infected cells. Although ICP0 is exclusively nuclear during the immediate-early phase of HSV infection, further analysis revealed that ICP0 translocated to the cytoplasm during the early phase where it triggered a previously unrecognized process; ICP0 dismantled the microtubule network of the host cell. A RING finger mutant of ICP0 efficiently bundled microtubules, but failed to disperse microtubule bundles. Synthesis of ICP0 proved to be necessary and sufficient to disrupt microtubule networks in HSV-infected and transfected cells. Plant and animal viruses encode many proteins that reorganize microtubules. However, this is the first report of a viral E3 ligase that regulates microtubule stability. Intriguingly, several cellular E3 ligases orchestrate microtubule disassembly and reassembly during mitosis. Our results suggest that ICP0 serves a dual role in the HSV life cycle, acting first as a nuclear regulator of viral mRNA synthesis and acting later, in the cytoplasm, to dismantle the host cell's microtubule network in preparation for virion synthesis and/or egress.

  10. Inhibition of MHC class I is a virulence factor in herpes simplex virus infection of mice.

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    Mark T Orr

    2005-09-01

    Full Text Available Herpes simplex virus (HSV has a number of genes devoted to immune evasion. One such gene, ICP47, binds to the transporter associated with antigen presentation (TAP 1/2 thereby preventing transport of viral peptides into the endoplasmic reticulum, loading of peptides onto nascent major histocompatibility complex (MHC class I molecules, and presentation of peptides to CD8 T cells. However, ICP47 binds poorly to murine TAP1/2 and so inhibits antigen presentation by MHC class I in mice much less efficiently than in humans, limiting the utility of murine models to address the importance of MHC class I inhibition in HSV immunopathogenesis. To address this limitation, we generated recombinant HSVs that efficiently inhibit antigen presentation by murine MHC class I. These recombinant viruses prevented cytotoxic T lymphocyte killing of infected cells in vitro, replicated to higher titers in the central nervous system, and induced paralysis more frequently than control HSV. This increase in virulence was due to inhibition of antigen presentation to CD8 T cells, since these differences were not evident in MHC class I-deficient mice or in mice in which CD8 T cells were depleted. Inhibition of MHC class I by the recombinant viruses did not impair the induction of the HSV-specific CD8 T-cell response, indicating that cross-presentation is the principal mechanism by which HSV-specific CD8 T cells are induced. This inhibition in turn facilitates greater viral entry, replication, and/or survival in the central nervous system, leading to an increased incidence of paralysis.

  11. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Kai [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of Life Science and Technology, Jinan University, Guangzhou (China); Chen, Maoyun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Xiang, Yangfei; Ma, Kaiqi [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Jin, Fujun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Wang, Xiao [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Wang, Xiaoyan; Wang, Shaoxiang [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Wang, Yifei, E-mail: twang-yf@163.com [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China)

    2014-04-18

    Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.

  12. Assessing the contribution of the herpes simplex virus DNA polymerase to spontaneous mutations

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    Leary Jeffry J

    2002-05-01

    Full Text Available Abstract Background The thymidine kinase (tk mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (HSV replication-mediated mutations. Using this assay, clinical and laboratory HSV-2 isolates were shown to have a 10- to 80-fold higher frequency of spontaneous mutations compared to HSV-1. Methods A panel of HSV-1 and HSV-2, along with polymerase-recombinant viruses expressing type 2 polymerase (Pol within a type 1 genome, were evaluated using the tk and non-HSV DNA mutagenesis assays to measure HSV replication-dependent errors and determine whether the higher mutation frequency of HSV-2 is a distinct property of type 2 polymerases. Results Although HSV-2 have mutation frequencies higher than HSV-1 in the tk assay, these errors are assay-specific. In fact, wild type HSV-1 and the antimutator HSV-1 PAAr5 exhibited a 2–4 fold higher frequency than HSV-2 in the non-HSV DNA mutatagenesis assay. Furthermore, regardless of assay, HSV-1 recombinants expressing HSV-2 Pol had error rates similar to HSV-1, whereas the high mutator virus, HSV-2 6757, consistently showed signficant errors. Additionally, plasmid DNA containing the HSV-2 tk gene, but not type 1 tk or LacZ DNA, was shown to form an anisomorphic DNA stucture. Conclusions This study suggests that the Pol is not solely responsible for the virus-type specific differences in mutation frequency. Accordingly, it is possible that (a mutations may be modulated by other viral polypeptides cooperating with Pol, and (b the localized secondary structure of the viral genome may partially account for the apparently enhanced error frequency of HSV-2.

  13. Identification of an immunodominant epitope in glycoproteins B and G of herpes simplex viruses (HSVs) using synthetic peptides as antigens in assay of antibodies to HSV in herpes simplex encephalitis patients.

    Science.gov (United States)

    Bhullar, S S; Chandak, N H; Baheti, N N; Purohit, H J; Taori, G M; Daginawala, H F; Kashyap, R S

    2014-01-01

    Herpes simplex encephalitis (HSE) is a severe viral infection of the central nervous system (CNS). Assay of antibody response is widely used in diagnostics of HSE. The aim of this study was to identify an immunodominant epitope determining the antibody response to herpes simplex viruses (HSVs) in cerebrospinal fluid (CSF) of HSE patients. The synthetic peptides that resembled type-common as well as type-specific domains of glycoproteins B (gB) and G (gG) of these viruses were evaluated for binding with IgM and IgG antibodies in CSF samples from HSE and non-HSE patients in ELISA. The QLHDLRF peptide, derived from gB of HSV was found to be an immunodominant epitope in the IgM and IgG antibody response. The patients with confirmed and suspected HSE showed in ELISA against this peptide 26% and 23% positivities for IgM, 43% and 37% positivities for IgG and 17% and 15% for both IgM and IgG antibodies, respectively. The total positivities of 86% and 75% for both IgM and IgG antibodies were obtained in the patients with confirmed and suspected HSE, respectively. These results demonstrate that a synthetic peptide-based diagnostics of HSE can be an efficient and easily accessible alternative. This is the first report describing the use of synthetic peptides derived from HSVs in diagnostics of HSE using patientsʹ CSF samples.

  14. The management of herpes simplex virus infections in HIV infected patients: current issues and the role of cidofovir

    Directory of Open Access Journals (Sweden)

    Nakakawa E

    2011-06-01

    Full Text Available Ethel Nakakawa1, Steven J Reynolds21Makerere University College of Health Sciences, Department of Microbiology, Kampala, Uganda; 2Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD and Johns Hopkins University School of Medicine, Baltimore, MD, USAAbstract: Herpes simplex virus (HSV type 1 and 2 are among the most common transmitted viral infections causing a spectrum of mucocutaneous and other syndromes. Treatment of these infections has primarily been with acyclovir (ACV and prodrugs valacyclovir and famcyclovir. Immunocompromised hosts either due to human immunodeficiency virus (HIV or other factors have given rise to an increase in ACV resistant viruses most commonly due to a mutation in the cellular thymidine kinase enzyme. This review focuses on the spectrum of disease caused by HSV 1 and 2, the emergence of ACV resistant disease, and the role of alternative agents including cidofovir in the treatment of ACV resistant disease.Keywords: herpes simplex virus, HIV, resistance, cidofovir

  15. Incorporation of a lambda phage recombination system and EGFP detection to simplify mutagenesis of Herpes simplex virus bacterial artificial chromosomes

    Directory of Open Access Journals (Sweden)

    Weir Jerry P

    2007-05-01

    Full Text Available Abstract Background Targeted mutagenesis of the herpesvirus genomes has been facilitated by the use of bacterial artificial chromosome (BAC technology. Such modified genomes have potential uses in understanding viral pathogenesis, gene identification and characterization, and the development of new viral vectors and vaccines. We have previously described the construction of a herpes simplex virus 2 (HSV-2 BAC and the use of an allele replacement strategy to construct HSV-2 recombinants. While the BAC mutagenesis procedure is a powerful method to generate HSV-2 recombinants, particularly in the absence of selective marker in eukaryotic culture, the mutagenesis procedure is still difficult and cumbersome. Results Here we describe the incorporation of a phage lambda recombination system into an allele replacement vector. This strategy enables any DNA fragment containing the phage attL recombination sites to be efficiently inserted into the attR sites of the allele replacement vector using phage lambda clonase. We also describe how the incorporation of EGFP into the allele replacement vector can facilitate the selection of the desired cross-over recombinant BACs when the allele replacement reaction is a viral gene deletion. Finally, we incorporate the lambda phage recombination sites directly into an HSV-2 BAC vector for direct recombination of gene cassettes using the phage lambda clonase-driven recombination reaction. Conclusion Together, these improvements to the techniques of HSV BAC mutagenesis will facilitate the construction of recombinant herpes simplex viruses and viral vectors.

  16. Oral ulcers in children under chemotherapy: clinical characteristics and their relation with Herpes Simplex Virus type 1 and Candida albicans.

    Science.gov (United States)

    Sepúlveda, Ester; Brethauer, Ursula; Rojas, Jaime; Fernández, Eduardo; Le Fort, Patricia

    2005-04-01

    The objective of this study was to determine the clinical characteristics of oral ulcers in pediatric oncology patients undergoing chemotherapy and their relation with the presence of Herpes Simplex Virus (HSV) type 1 and Candida albicans. The sample consisted of 20 ulcerative lesions from 15 children treated with chemotherapy in the Pediatric Service of the Regional Hospital of Concepción, Chile. Two calibrated clinicians performed clinical diagnosis of the ulcers and registered general data from the patients (age, general diagnosis, absolute neutrophil count, and number of days after chemotherapy) and clinical characteristic of the ulcers: number, size, location, presence or absence of pain and inflammatory halo, edge characteristics, and exudate type. Additional to clinical diagnosis, culture for Candida albicans (C) and polymerase chain reaction (PCR) for Herpes Simplex Virus type 1 was performed. Ten ulcers occurred in patients with acute lymphoblastic leukemia, five in patients with acute myeloblastic leukemia and five in patients with other neoplastic diseases. Eight ulcers were HSV (+) / C (-), 6 HSV (-) / C (-), 4 HSV (+) / C (+) and 2 HSV (-) / C (+). Preferential location was the hard palate. Most lesions were multiple, painful, with inflammatory halo, irregular edges and fibrinous exudate. The average size was 6,5 millimeters, and the mean number of days after chemotherapy was 7.5 days. Oral ulcers in children with oncological diseases did not present a specific clinical pattern. They were strongly associated with HSV.

  17. Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Ying, E-mail: peiying-19802@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Chen, Zhen-Ping, E-mail: 530670663@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Ju, Huai-Qiang, E-mail: 344464448@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Komatsu, Masaaki, E-mail: komatsu-ms@igakuken.or.jp [Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613 (Japan); Ji, Yu-hua, E-mail: tjyh@jnu.edu.cn [Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Liu, Ge, E-mail: lggege_15@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Guo, Chao-wan, E-mail: chaovan_kwok@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Zhang, Ying-Jun, E-mail: zhangyj@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Yang, Chong-Ren, E-mail: cryang@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Wang, Yi-Fei, E-mail: twang-yf@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Kitazato, Kaio, E-mail: kkholi@msn.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan)

    2011-02-11

    Research highlights: {yields} We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. {yields} Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. {yields} Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7{sup -/-} cells (autophagy-defective cells) derived from an atg7{sup -/-} knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

  18. Safety and tolerability of combination acyclovir 5% and hydrocortisone 1% cream in adolescents with recurrent herpes simplex labialis.

    Science.gov (United States)

    Strand, Anders; Böttiger, Disa; Gever, Larry N; Wheeler, William

    2012-01-01

    A Phase 3, open-label, multicenter study was conducted to assess the safety of the combination of 5% acyclovir and 1% hydrocortisone cream (AHC cream) in the treatment of recurrent herpes simplex labialis (HSL) in immunocompetent adolescents. Eligible subjects were aged 12 to 17 years and had a history of recurrent labial herpes with two or more episodes during the last 12 months. Subjects initiated treatment at the first signs or symptoms of a herpes recurrence-at the earliest prodromal phase and preferably before the presence of papules or vesicles. Subjects applied the cream topically five times per day for 5 days. Adverse events, categorization of recurrence (ulcerative or nonulcerative), and maximum lesion area (maximum area of an ulcerative lesion) were assessed. Of the 134 subjects analyzed for safety, 131 had data for categorization of recurrence at the post-treatment visit 3 ± 1 weeks after the last dose. Seventy-eight subjects (59.5%) had nonulcerative recurrences, and 53 (40.5%) had ulcerative recurrences. All 131 subjects reached the stage of normal skin, with no signs or symptoms, at the follow-up visit. The mean maximum lesion area in the 53 subjects with ulcerative herpes lesion was 39 mm(2). Five subjects reported five adverse events (secondary herpes labialis recurrences, n = 2; infectious rhinitis, n = 1; application site inflammation, n = 1; bronchial asthma, n = 1). All adverse events were of mild to moderate intensity. The results of this study demonstrate that the combination of AHC cream is well tolerated in the treatment of recurrent HSL in adolescents.

  19. Herpes simplex virus infection is sensed by both Toll-like receptors and retinoic acid-inducible gene- like receptors, which synergize to induce type I interferon production

    DEFF Research Database (Denmark)

    Rasmussen, Simon Brandtoft; Jensen, Søren B; Nielsen, C;

    2009-01-01

    interferons (IFNs) after infection with herpes simplex virus (HSV). Our work also identified RNase L as a critical component in IFN induction. Moreover, we found that TLR9 and RLRs activate distinct, as well as overlapping, intracellular signalling pathways. Thus, RLRs are important for recognition of HSV...

  20. Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells

    NARCIS (Netherlands)

    L. Remeijer (Lies); C.M. Mooy (Cornelia); A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George)

    2000-01-01

    textabstractPURPOSE: Herpetic stromal keratitis (HSK) is a T-cell-mediated inflammatory disease initiated by a herpes simplex virus (HSV) infection of the cornea. Recently, studies in the HSK mouse model have shown that the immunopathogenic T cells are directed against the HSV prot

  1. Consequences of chemoresistance for the herpes simplex virus thymidine kinase/ganciclovir-induced bystander effect in a human small cell lung cancer cell line model

    NARCIS (Netherlands)

    Van Dillen, IJ; Mulder, NH; Sluiter, WJ; Meijer, C; De Jong, S; Loncarek, J; Mesnil, M; De Vries, EFJ; Vaalburg, W; Hospers, GAP

    2005-01-01

    This paper focuses on the influence of chemoresistance on the herpes simplex virus (HSVtk)/ganciclovir (GCV)-induced bystander effect (BE), as studied in a human small cell lung cancer (SCLC) cell line (GLC(4)) and its sublines with in vitro acquired resistance to adriamycin (GLC(4)/ADR),

  2. High level expression and secretion of truncated forms of herpes simplex virus type I and type 2 glycoprotein D by the methylotrophic yeast Pichia pastoris

    NARCIS (Netherlands)

    van Kooij, A; Middel, J; Jakab, F; Elfferich, P; Koedijk, DGAM; Feijlbrief, M; Scheffer, AJ; Degener, JE; The, TH; Scheek, RM; Welling, GW; Welling-Wester, S

    Herpes simplex virus type I and 2 (HSV-1 and -2) glycoproteins D (gD-1 and gD-2) play a role in the entry of the virus into the host cell. Availability of substantial amounts of these proteins, or large fragments thereof. will he needed to allow studies at the molecular level. We studied the potency

  3. Comparison of two enzyme-linked immunosorbent assays and one rapid immunoblot assay for detection of herpes simplex virus type 2-specific antibodies in serum

    NARCIS (Netherlands)

    J. Groen (Jan); G. van Dijk (Grietje); H.G.M. Niesters (Bert); W.I. van der Meijden (Willem); A.D.M.E. Osterhaus (Albert)

    1998-01-01

    textabstractThe sensitivities and specificities of three immunoassays for the detection of herpes simplex virus type 2 (HSV-2)-specific immunoglobulin G antibodies in serum, including the one-strip rapid immunoblot assay (RIBA; Chiron Corporation) and two indirect enzyme

  4. Comparison of two enzyme-linked immunosorbent assays and one rapid immunoblot assay for detection of herpes simplex virus type 2-specific antibodies in serum

    NARCIS (Netherlands)

    Groen, J; Van Dijk, G; Niesters, H G; Van Der Meijden, W I; Osterhaus, A D

    The sensitivities and specificities of three immunoassays for the detection of herpes simplex virus type 2 (HSV-2)-specific immunoglobulin G antibodies in serum, including the one-strip rapid immunoblot assay (RIBA; Chiron Corporation) and two indirect enzyme immunosorbent assays (EIA; Gull

  5. [C-11]FMAU and [F-18]FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections

    NARCIS (Netherlands)

    de Vries, EFJ; van Waarde, A; Harmsen, MC; Mulder, NH; Vaalburg, W; Hospers, GAP

    [C-11]-2'-Fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ([C-11]FMAU) and [F-18]-9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([F-18]FHPG), radiolabeled representatives of two classes of antiviral agents, were evaluated as tracers for measuring herpes simplex virus thymidine kinase (HSV-tk)

  6. F-18-FEAU as a radiotracer for herpes simplex virus thymidine kinase gene expression : in-vitro comparison with other PET tracers

    NARCIS (Netherlands)

    Buursma, AR; Rutgers, [No Value; Hospers, GAP; Mulder, NH; Vaalburg, W; de Vries, EFJ

    Objective The herpes simplex virus thymidine kinase (HSVtk) gene has frequently been applied as a reporter gene for monitoring transgene expression in animal models. In clinical gene therapy protocols, however, extremely low expression levels of the transferred gene are generally observed.

  7. Association of GRIN1 and GRIN2A-D With schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk

    DEFF Research Database (Denmark)

    Demontis, Ditte; Nyegaard, Mette; Buttenschøn, Henriette N

    2011-01-01

    in the offspring interacted with maternal herpes simplex virus-2 (HSV-2) seropositivity during pregnancy influencing the risk of schizophrenia later in life. Individuals from three independently collected Danish case control samples were genotyped for 81 tagSNPs (in total 984 individuals diagnosed...

  8. Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells

    DEFF Research Database (Denmark)

    Zhang, Wen; Bao, Li; Yang, Shaoxing

    2016-01-01

    Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase...

  9. Detergent extraction of herpes simplex virus type 1 glycoprotein D by zwitterionic and non-ionic detergents and purification by ion-exchange high-performance liquid chromatography

    NARCIS (Netherlands)

    Welling-Wester, S; Feijlbrief, M; Koedijk, DGAM; Welling, GW

    1998-01-01

    Detergents (surfactants) are the key reagents in the extraction and purification of integral membrane proteins. Zwitterionic and non-ionic detergents were used for the extraction of recombinant glycoprotein D (gD-1) of herpes simplex virus type 1 (HSV-1) from insect cells infected with recombinant b

  10. IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

    Science.gov (United States)

    Thomas, Eric D; Meza-Perez, Selene; Bevis, Kerri S; Randall, Troy D; Gillespie, G Yancey; Langford, Catherine; Alvarez, Ronald D

    2016-10-27

    Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8(+) T cell response in the omentum and peritoneal cavity. All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8(+) T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated

  11. Herpes Simplex Virus Dances with Amyloid Precursor Protein while Exiting the Cell

    Science.gov (United States)

    Cheng, Shi-Bin; Ferland, Paulette; Webster, Paul; Bearer, Elaine L.

    2011-01-01

    Herpes simplex type 1 (HSV1) replicates in epithelial cells and secondarily enters local sensory neuronal processes, traveling retrograde to the neuronal nucleus to enter latency. Upon reawakening newly synthesized viral particles travel anterograde back to the epithelial cells of the lip, causing the recurrent cold sore. HSV1 co-purifies with amyloid precursor protein (APP), a cellular transmembrane glycoprotein and receptor for anterograde transport machinery that when proteolyzed produces A-beta, the major component of senile plaques. Here we focus on transport inside epithelial cells of newly synthesized virus during its transit to the cell surface. We hypothesize that HSV1 recruits cellular APP during transport. We explore this with quantitative immuno-fluorescence, immuno-gold electron-microscopy and live cell confocal imaging. After synchronous infection most nascent VP26-GFP-labeled viral particles in the cytoplasm co-localize with APP (72.8+/−6.7%) and travel together with APP inside living cells (81.1+/−28.9%). This interaction has functional consequences: HSV1 infection decreases the average velocity of APP particles (from 1.1+/−0.2 to 0.3+/−0.1 µm/s) and results in APP mal-distribution in infected cells, while interplay with APP-particles increases the frequency (from 10% to 81% motile) and velocity (from 0.3+/−0.1 to 0.4+/−0.1 µm/s) of VP26-GFP transport. In cells infected with HSV1 lacking the viral Fc receptor, gE, an envelope glycoprotein also involved in viral axonal transport, APP-capsid interactions are preserved while the distribution and dynamics of dual-label particles differ from wild-type by both immuno-fluorescence and live imaging. Knock-down of APP with siRNA eliminates APP staining, confirming specificity. Our results indicate that most intracellular HSV1 particles undergo frequent dynamic interplay with APP in a manner that facilitates viral transport and interferes with normal APP transport and distribution. Such dynamic

  12. Association between IgM anti-herpes simplex virus and plasma amyloid-beta levels.

    Directory of Open Access Journals (Sweden)

    Catherine Féart

    Full Text Available OBJECTIVE: Herpes simplex virus (HSV reactivation has been identified as a possible risk factor for Alzheimer's disease (AD and plasma amyloid-beta (Aβ levels might be considered as possible biomarkers of the risk of AD. The aim of our study was to investigate the association between anti-HSV antibodies and plasma Aβ levels. METHODS: The study sample consisted of 1222 subjects (73.9 y in mean from the Three-City cohort. IgM and IgG anti-HSV antibodies were quantified using an ELISA kit, and plasma levels of Aβ(1-40 and Aβ(1-42 were measured using an xMAP-based assay technology. Cross-sectional analyses of the associations between anti-HSV antibodies and plasma Aβ levels were performed by multi-linear regression. RESULTS: After adjustment for study center, age, sex, education, and apolipoprotein E-e4 polymorphism, plasma Aβ(1-42 and Aβ(1-40 levels were specifically inversely associated with anti-HSV IgM levels (β = -20.7, P=0.001 and β = -92.4, P=0.007, respectively. In a sub-sample with information on CLU- and CR1-linked SNPs genotyping (n=754, additional adjustment for CR1 or CLU markers did not modify these associations (adjustment for CR1 rs6656401, β = -25.6, P=0.002 for Aβ(1-42 and β = -132.7, P=0.002 for Aβ(1-40; adjustment for CLU rs2279590, β = -25.6, P=0.002 for Aβ(1-42 and β = -134.8, P=0.002 for Aβ(1-40. No association between the plasma Aβ(1-42-to-Aβ(1-40 ratio and anti-HSV IgM or IgG were evidenced. CONCLUSION: High anti-HSV IgM levels, markers of HSV reactivation, are associated with lower plasma Aβ(1-40 and Aβ(1-42 levels, which suggest a possible involvement of the virus in the alterations of the APP processing and potentially in the pathogenesis of AD in human.

  13. Infiltration Pattern of Blood Monocytes into the Central Nervous System during Experimental Herpes Simplex Virus Encephalitis.

    Directory of Open Access Journals (Sweden)

    Rafik Menasria

    Full Text Available The kinetics and distribution of infiltrating blood monocytes into the central nervous system and their involvement in the cerebral immune response together with resident macrophages, namely microglia, were evaluated in experimental herpes simplex virus 1 (HSV-1 encephalitis (HSE. To distinguish microglia from blood monocyte-derived macrophages, chimeras were generated by conditioning C57BL/6 recipient mice with chemotherapy regimen followed by transplantation of bone morrow-derived cells that expressed the green fluorescent protein. Mice were infected intranasally with a sub-lethal dose of HSV-1 (1.2 x 10(6 plaque forming units. Brains were harvested prior to and on days 4, 6, 8 and 10 post-infection for flow cytometry and immunohistochemistry analysis. The amounts of neutrophils (P < 0.05 and "Ly6C hi" inflammatory monocytes (P < 0.001 significantly increased in the CNS compared to non-infected controls on day 6 post-infection, which corresponded to more severe clinical signs of HSE. Levels decreased on day 8 for both leukocytes subpopulations (P < 0.05 for inflammatory monocytes compared to non-infected controls to reach baseline levels on day 10 following infection. The percentage of "Ly6C low" patrolling monocytes significantly increased (P < 0.01 at a later time point (day 8, which correlated with the resolution phase of HSE. Histological analysis demonstrated that blood leukocytes colonized mostly the olfactory bulb and the brainstem, which corresponded to regions where HSV-1 particles were detected. Furthermore, infiltrating cells from the monocytic lineage could differentiate into activated local tissue macrophages that express the microglia marker, ionized calcium-binding adaptor molecule 1. The lack of albumin detection in the brain parenchyma of infected mice showed that the infiltration of blood leukocytes was not necessarily related to a breakdown of the blood-brain barrier but could be the result of a functional recruitment. Thus

  14. Infiltration Pattern of Blood Monocytes into the Central Nervous System during Experimental Herpes Simplex Virus Encephalitis

    Science.gov (United States)

    Menasria, Rafik; Canivet, Coraline; Piret, Jocelyne; Boivin, Guy

    2015-01-01

    The kinetics and distribution of infiltrating blood monocytes into the central nervous system and their involvement in the cerebral immune response together with resident macrophages, namely microglia, were evaluated in experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE). To distinguish microglia from blood monocyte-derived macrophages, chimeras were generated by conditioning C57BL/6 recipient mice with chemotherapy regimen followed by transplantation of bone morrow-derived cells that expressed the green fluorescent protein. Mice were infected intranasally with a sub-lethal dose of HSV-1 (1.2x106 plaque forming units). Brains were harvested prior to and on days 4, 6, 8 and 10 post-infection for flow cytometry and immunohistochemistry analysis. The amounts of neutrophils (P<0.05) and «Ly6Chi» inflammatory monocytes (P<0.001) significantly increased in the CNS compared to non-infected controls on day 6 post-infection, which corresponded to more severe clinical signs of HSE. Levels decreased on day 8 for both leukocytes subpopulations (P<0.05 for inflammatory monocytes compared to non-infected controls) to reach baseline levels on day 10 following infection. The percentage of «Ly6Clow» patrolling monocytes significantly increased (P<0.01) at a later time point (day 8), which correlated with the resolution phase of HSE. Histological analysis demonstrated that blood leukocytes colonized mostly the olfactory bulb and the brainstem, which corresponded to regions where HSV-1 particles were detected. Furthermore, infiltrating cells from the monocytic lineage could differentiate into activated local tissue macrophages that express the microglia marker, ionized calcium-binding adaptor molecule 1. The lack of albumin detection in the brain parenchyma of infected mice showed that the infiltration of blood leukocytes was not necessarily related to a breakdown of the blood-brain barrier but could be the result of a functional recruitment. Thus, our findings suggest

  15. Global estimates of prevalent and incident herpes simplex virus type 2 infections in 2012.

    Directory of Open Access Journals (Sweden)

    Katharine J Looker

    Full Text Available Herpes simplex virus type 2 (HSV-2 infection causes significant disease globally. Adolescent and adult infection may present as painful genital ulcers. Neonatal infection has high morbidity and mortality. Additionally, HSV-2 likely contributes substantially to the spread of HIV infection. The global burden of HSV-2 infection was last estimated for 2003. Here we present new global estimates for 2012 of the burden of prevalent (existing and incident (new HSV-2 infection among females and males aged 15-49 years, using updated methodology to adjust for test performance and estimate by World Health Organization (WHO region.We conducted a literature review of HSV-2 prevalence studies world-wide since 2000. We then fitted a model with constant HSV-2 incidence by age to pooled HSV-2 prevalence values by age and sex. Prevalence values were adjusted for test sensitivity and specificity. The model estimated prevalence and incidence by sex for each WHO region to obtain global burden estimates. Uncertainty bounds were computed by refitting the model to reflect the variation in the underlying prevalence data. In 2012, we estimate that there were 417 million people aged 15-49 years (range: 274-678 million living with HSV-2 infection world-wide (11.3% global prevalence, of whom 267 million were women. We also estimate that in 2012, 19.2 million (range: 13.0-28.6 million individuals aged 15-49 years were newly-infected (0.5% of all individuals globally. The highest burden was in Africa. However, despite lower prevalence, South-East Asia and Western Pacific regions also contributed large numbers to the global totals because of large population sizes.The global burden of HSV-2 infection is large, leaving over 400 million people at increased risk of genital ulcer disease, HIV acquisition, and transmission of HSV-2 to partners or neonates. These estimates highlight the critical need for development of vaccines, microbicides, and other new HSV prevention strategies.

  16. The identities and anti-herpes simplex virus activity of Clinacanthusnutans and Clinacanthus siamensis

    Institute of Scientific and Technical Information of China (English)

    Paween Kunsorn; Nijsiri Ruangrungsi; Vimolmas Lipipun; Ariya Khanboon; Kanchana Rungsihirunrat

    2013-01-01

    Objective: To distinguish the difference among the Clinacanthus nutans (Burm. f.) Lindau (C. nutans) and Clinacanthus siamensis Bremek (C. siamensis) by assessing pharmacognosy characteristics, molecular aspect and also to evaluate their anti-herpes simplex virus (HSV) type 1 and type 2 activities. Methods: Macroscopic and microscopic evaluation were performed according to WHO Geneva guideline. Stomatal number, stomatal index and palisade ratio of leaves were evaluated. Genomic DNA was extracted by modified CTAB method and ITS region was amplified using PCR and then sequenced. Dry leaves were subsequently extracted withn-hexane, dichloromethane and methanol and antiviral activity was performed using plaque reduction assay and the cytotoxicity of the extracts on Vero cells was determined by MTT assay. Results: Cross section of midrib and stem showed similar major components. Leaf measurement index of stomatal number, stomatal index and palisade ratio of C. nutans were 168.32±29.49, 13.83±0.86 and 6.84±0.66, respectively, while C. siamensis were 161.60±18.04, 11.93±0.81 and 3.37±0.31, respectively. The PCR amplification of ITS region generated the PCR product approximately 700 bp in size. There were 34 polymorphisms within the ITS region which consisted of 11 Indels and 23 nucleotide substitutions. The IC50 values of C. nutans extracted with n-hexane, dichloromethane and methanol against HSV-1 were (32.05±3.63) µg/mL, (44.50±2.66) µg/mL, (64.93±7.00) µg/mL, respectively where as those of C. siamensis were (60.00±11.61) µg/mL, (55.69±4.41) µg/mL, (37.39±5.85) µg/mL, respectively. Anti HSV-2 activity of n-hexane, dichloromethane and methanolC. nutans leaves extracts were (72.62±12.60) µg/mL, (65.19±21.45) µg/mL, (65.13±2.22) µg/mL, respectively where as those of C. siamensis were (46.52±4.08) µg/mL, (49.63±2.59) µg/mL, (72.64±6.52) µg/mL, respectively. Conclusions: The combination of macroscopic, microscopic and biomolecular method are

  17. Cellular Cholesterol Facilitates the Postentry Replication Cycle of Herpes Simplex Virus 1.

    Science.gov (United States)

    Wudiri, George A; Nicola, Anthony V

    2017-07-15

    Cholesterol is an essential component of cell membranes and is required for herpes simplex virus 1 (HSV-1) entry (1-3). Treatment of HSV-1-infected Vero cells with methyl beta-cyclodextrin from 2 to 9 h postentry reduced plaque numbers. Transport of incoming viral capsids to the nuclear periphery was unaffected by the cholesterol reduction, suggesting that cell cholesterol is important for the HSV-1 replicative cycle at a stage(s) beyond entry, after the arrival of capsids at the nucleus. The synthesis and release of infectious HSV-1 and cell-to-cell spread of infection were all impaired in cholesterol-reduced cells. Propagation of HSV-1 on DHCR24(-/-) fibroblasts, which lack the desmosterol-to-cholesterol conversion enzyme, resulted in the generation of infectious extracellular virions (HSV(des)) that lack cholesterol and likely contain desmosterol. The specific infectivities (PFU per viral genome) of HSV(chol) and HSV(des) were similar, suggesting cholesterol and desmosterol in the HSV envelope support similar levels of infectivity. However, infected DHCR24(-/-) fibroblasts released ∼1 log less infectious HSV(des) and ∼1.5 log fewer particles than release of cholesterol-containing particles (HSV(chol)) from parental fibroblasts, suggesting that the hydrocarbon tail of cholesterol facilitates viral synthesis. Together, the results suggest multiple roles for cholesterol in the HSV-1 replicative cycle.IMPORTANCE HSV-1 infections are associated with a wide range of clinical manifestations that are of public health importance. Cholesterol is a key player in the complex interaction between viral and cellular factors that allows HSV-1 to enter host cells and establish infection. Previous reports have demonstrated a role for cellular cholesterol in the entry of HSV-1 into target cells. Here, we employed both chemical treatment and cells that were genetically defined to synthesize only desmosterol to demonstrate that cholesterol is important at stages following the

  18. Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas

    Science.gov (United States)

    Duggal, Neil; Jaishankar, Dinesh; Yadavalli, Tejabhiram; Hadigal, Satvik; Mishra, Yogendra Kumar; Adelung, Rainer

    2017-01-01

    Purpose Infection of the human cornea by herpes simplex virus type-1 (HSV-1) can cause significant vision loss. The purpose of this study was to develop an ex vivo model to visualize viral growth and spread in the cornea. The model was also used to analyze cytokine production and study the antiviral effects of zinc oxide tetrapods. Methods A β-galactosidase-expressing recombinant virus, HSV-1(KOS)tk12, was used to demonstrate the ability of the virus to enter and develop blue plaques on human corneal epithelial (HCE) cells and corneal tissues. Freshly obtained porcine corneas were cultured and then scratched before infection with HSV-1(KOS)tk12. The blue plaques on the corneas were imaged using a stereomicroscope. Western blot analysis for HSV-1 proteins was performed to verify HSV-1 infection of the cornea. Using the ex vivo model, zinc oxide tetrapods were tested for their anti-HSV-1 potential, and a cytokine profile was developed to assess the effects of the treatment. Results Cultured corneas and the use of β-galactosidase-expressing HSV-1(KOS)tk12 virus can provide an attractive ex vivo model to visualize and study HSV-1 entry and spread of the infection in tissues. We found that unlike cultured HCE cells, which demonstrated nearly 100% infectivity, HSV-1 infection of the cultured cornea was more restrictive and took longer to develop. We also found that the zinc oxide tetrapod–shaped nano- and microstructures inhibited HSV infection of the cultured cells, as well as the cultured corneas. The cytokine profile of the infected samples was consistent with previous studies of HSV-1 corneal infection. Conclusions The ability to visualize HSV-1 growth and spread in corneal tissues can provide new details about HSV-1 infection of the cornea and the efficacy of new cornea-specific antiviral drug candidates. The ex vivo model also demonstrates antiviral effects of zinc oxide tetrapods and adequately portrays the drug delivery issues that cornea-specific treatments

  19. Dissection of the Antibody Response against Herpes Simplex Virus Glycoproteins in Naturally Infected Humans

    Science.gov (United States)

    Huang, Zhen-Yu; Whitbeck, J. Charles; Ponce de Leon, Manuel; Lou, Huan; Wald, Anna; Krummenacher, Claude; Eisenberg, Roselyn J.; Cohen, Gary H.

    2014-01-01

    ABSTRACT Relatively little is known about the extent of the polyclonal antibody (PAb) repertoire elicited by herpes simplex virus (HSV) glycoproteins during natural infection and how these antibodies affect virus neutralization. Here, we examined IgGs from 10 HSV-seropositive individuals originally classified as high or low virus shedders. All PAbs neutralized virus to various extents. We determined which HSV entry glycoproteins these PAbs were directed against: glycoproteins gB, gD, and gC were recognized by all sera, but fewer sera reacted against gH/gL. We previously characterized multiple mouse monoclonal antibodies (MAbs) and mapped those with high neutralizing activity to the crystal structures of gD, gB, and gH/gL. We used a biosensor competition assay to determine whether there were corresponding human antibodies to those epitopes. All 10 samples had neutralizing IgGs to gD epitopes, but there were variations in which epitopes were seen in individual samples. Surprisingly, only three samples contained neutralizing IgGs to gB epitopes. To further dissect the nature of these IgGs, we developed a method to select out gD- and gB-specific IgGs from four representative sera via affinity chromatography, allowing us to determine the contribution of antibodies against each glycoprotein to the overall neutralization capacity of the serum. In two cases, gD and gB accounted for all of the neutralizing activity against HSV-2, with a modest amount of HSV-1 neutralization directed against gC. In the other two samples, the dominant response was to gD. IMPORTANCE Antibodies targeting functional epitopes on HSV entry glycoproteins mediate HSV neutralization. Virus-neutralizing epitopes have been defined and characterized using murine monoclonal antibodies. However, it is largely unknown whether these same epitopes are targeted by the humoral response to HSV infection in humans. We have shown that during natural infection, virus-neutralizing antibodies are principally

  20. The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features

    Science.gov (United States)

    Fan, Shengtao; Cai, Hongzhi; Xu, Xingli; Feng, Min; Wang, Lichun; Liao, Yun; Zhang, Ying; He, Zhanlong; Yang, Fengmei; Yu, Wenhai; Wang, Jingjing; Zhou, Jumin; Li, Qihan

    2017-01-01

    As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1. Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection, and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG) on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues. PMID:28146109

  1. [IgM, IgG and IgG subclass antibodies to herpes simplex virus in persons of different ages].

    Science.gov (United States)

    Zazimko, L A; Kuzenkova, A V; Ivanova, I A; Bashukova, S S; Rybakov, V P; Klimovich, V B; Shitikova, G S

    2000-01-01

    IgM, IgG antibodies to herpes simplex virus and their subclases were investigated in 565 subjects of different age tested at virological laboratories of St. Petersburg in 1996-1997. The majority of these subjects had a history of herpes infection and 21.5% had IgM antibodies to herpes simplex virus (HSV), marker of acute herpetic infection. Besides IgM, IgG1 antibodies can be referred to early antibodies appearing during the acute stage of herpetic infection. The predominant subclass was HSV IgG3 antibodies. As for IgG4, they were completely absent in infants aged under 1 year, were detected in 6.2% children aged under 14 years, and were present in 12.2-12.5% adults.

  2. Phenotypic and Functional Characterization of Herpes Simplex Virus Glycoprotein B Epitope-Specific Effector and Memory CD8+ T Cells from Symptomatic and Asymptomatic Individuals with Ocular Herpes

    Science.gov (United States)

    Khan, Arif A.; Srivastava, Ruchi; Spencer, Doran; Garg, Sumit; Fremgen, Daniel; Vahed, Hawa; Lopes, Patricia P.; Pham, Thanh T.; Hewett, Charlie; Kuang, Jasmine; Ong, Nicolas; Huang, Lei; Scarfone, Vanessa M.; Nesburn, Anthony B.

    2015-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) glycoprotein B (gB)-specific CD8+ T cells protect mice from herpes infection and disease. However, whether and which HSV-1 gB-specific CD8+ T cells play a key role in the “natural” protection seen in HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we have dissected the phenotypes and the functions of HSV-1 gB-specific CD8+ T cells from HLA-A*02:01 positive, HSV-1 seropositive ASYMP and symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpes disease). We found the following. (i) Healthy ASYMP individuals maintained a significantly higher proportion of differentiated HSV-1 gB-specific effector memory CD8+ T cells (TEM cells) (CD45RAlow CCR7low CD44high CD62Llow). In contrast, SYMP patients had frequent less-differentiated central memory CD8+ T cells (TCM cells) (CD45RAlow CCR7high CD44low CD62Lhigh). (ii) ASYMP individuals had significantly higher proportions of multifunctional effector CD8+ T cells which responded mainly to gB342–350 and gB561–569 “ASYMP” epitopes, and simultaneously produced IFN-γ, CD107a/b, granzyme B, and perforin. In contrast, effector CD8+ T cells from SYMP individuals were mostly monofunctional and were directed mainly against nonoverlapping gB17–25 and gB183–191 “SYMP” epitopes. (iii) Immunization of an HLA-A*02:01 transgenic mouse model of ocular herpes with “ASYMP” CD8+ TEM cell epitopes, but not with “SYMP” CD8+ TCM cell epitopes, induced a strong CD8+ T cell-dependent protective immunity against ocular herpes infection and disease. Our findings provide insights into the role of HSV-specific CD8+ TEM cells in protection against herpes and should be considered in the development of an effective vaccine. IMPORTANCE A significantly higher proportion of differentiated and multifunctional HSV-1 gB-specific effector memory CD8+ T cells (TEM

  3. Encephalopathy

    Science.gov (United States)

    ... the brain that alters brain function or structure. Encephalopathy may be caused by infectious agent (bacteria, virus, or prion), metabolic or mitochondrial dysfunction, brain tumor or increased pressure in the ...

  4. No. 208-Guidelines for the Management of Herpes Simplex Virus in Pregnancy.

    Science.gov (United States)

    Money, Deborah M; Steben, Marc

    2017-08-01

    To provide recommendations for the management of genital herpes infection in women who want to get pregnant or are pregnant and for the management of genital herpes in pregnancy and strategies to prevent transmission to the infant. More effective management of complications of genital herpes in pregnancy and prevention of transmission of genital herpes from mother to infant. Medline was searched for articles published in French or English related to genital herpes and pregnancy. Additional articles were identified through the references of these articles. All study types and recommendation reports were reviewed. Recommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care. VALIDATION: These guidelines have been reviewed and approved by the Infectious Diseases Committee of the SOGC. The Society of Obstetricians and Gynaecologists of Canada. Copyright © 2017. Published by Elsevier Inc.

  5. Investigating the Relative Frequency of Infection with Herpes Simplex Virus Types 1 and 2 in the Serum of Patients with Multiple Sclerosis via Using Loop-mediated Isothermal Amplification (LAMP

    Directory of Open Access Journals (Sweden)

    A Atefi

    2014-02-01

    Conclusion: This study indicates that the LAMP technique owns high sensitivity and specificity for detection of herpes simplex virus types 1 and 2 in serum of patients with multiple sclerosis as well as the control group.

  6. Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens

    NARCIS (Netherlands)

    Engelmann, I.; Petzold, D. R.; Kosinska, A.; Hepkema, B. G.; Schulz, T. F.; Heim, A.

    Rapid diagnosis of human herpesvirus primary infections or reactivations is facilitated by quantitative PCRs. Quantitative PCR assays with a standard thermal cycling profile permitting simultaneous detection of herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV),

  7. Treatment of relapse in herpes simplex on labial and facial areas and of primary herpes simplex on genital areas and "area pudenda" with low-power He-Ne laser or Acyclovir administered orally

    Science.gov (United States)

    Velez-Gonzalez, Mariano; Urrea-Arbelaez, Alejandro; Nicolas, M.; Serra-Baldrich, E.; Perez, J. L.; Pavesi, M.; Camarasa, J. M.; Trelles, Mario A.

    1996-01-01

    Sixty patients (greater than 16 yrs old) suffering primary or relapse genital herpes simplex viruses (HSV) and relapse labial HSV were appointed for this study. Three or more relapses were experienced per year. Patients (under treatment) were divided into two groups (distribution areas), corresponding to either labial herpes or genital herpes. These groups were sub-divided into 3 groups. The total number of labial or facial HSV patients was 36 (10 in group 1, 12 in group 2, 14 in group 3) and 24 for genital, buttocks, or 'area pudenda' HSV patients (6 in group 1, 8 in group 2, 10 in group 3). The design was a randomized, double- blind study. The setting was hospital and outpatient. The patients diagnosed as having the HVS disease were sent to the dermatology department and were assigned to a group at random. Treatment was begun as follows: During the treatment signs and symptoms were assessed and after the treatment, the relapses were also assessed (biochemical and hematological tests before and after the treatment) and the diagnosis of the HSV type I and II. The statistical evaluation of the results was performed and carried out with the SPSS and BMDP program. The relapses of the herpes infection in the lips and the face were significantly reduced (p less than 0.026) in patients treated with laser He-Ne and laser He-Ne plus Acyclovir. The interim between the relapses also increased significantly (p less than 0.005) in relation with the group treated with Acyclovir. The duration of the herpetic eruptions was clearly reduced in all locations in patients treated with laser He-Ne plus Acyclovir. No differences were noted between patients treated with laser He-Ne only or Acyclovir only. Therefore it is probable that therapeutic synergism took place. In relation with this, laser He-Ne shows the same therapeutic efficacy as Acyclovir taken orally. The association of Acyclovir and laser Ne-Ne could be an alternative method for the treatment of HSV in the face. The number

  8. Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma: a case report and literature review.

    Science.gov (United States)

    Suzuki, Hiroshi I; Hangaishi, Akira; Hosoya, Noriko; Watanabe, Takuro; Kanda, Yoshinobu; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2008-06-01

    Neurological complications during the treatment of hematological malignancies have a wide range of causes. Treatment-related leukoencephalopathy has been recognized as a major complication of combined chemotherapy and radiotherapy for central nervous system (CNS) lymphoma, and can complicate the diagnosis of CNS infection. Herein, we present a patient with diffuse large B-cell lymphoma who developed herpes simplex encephalitis (HSE) and subsequent cytomegalovirus encephalitis after chemoradiotherapy for CNS relapse. Although cerebrospinal fluid examination (CSF) showed no significant pleocytosis, brain magnetic resonance imaging and polymerase chain reaction analysis of the CSF were useful in the diagnosis. With a review of the literature on the association between HSE and radiotherapy for CNS malignancies, our case suggests that an awareness of viral encephalitis is important in the differential diagnosis of acute neurologic disturbance during chemoradiotherapy for CNS lymphoma.

  9. A genome-wide comparative evolutionary analysis of herpes simplex virus type 1 and varicella zoster virus.

    Directory of Open Access Journals (Sweden)

    Peter Norberg

    Full Text Available Herpes simplex virus type 1 (HSV-1 and varicella zoster virus (VZV are closely related viruses causing lifelong infections. They are typically associated with mucocutaneous or skin lesions, but may also cause severe neurological or ophthalmic diseases, possibly due to viral- and/or host-genetic factors. Although these viruses are well characterized, genome-wide evolutionary studies have hitherto only been presented for VZV. Here, we present a genome-wide study on HSV-1. We also compared the evolutionary characteristics of HSV-1 with those for VZV. We demonstrate that, in contrast to VZV for which only a few ancient recombination events have been suggested, all HSV-1 genomes contain mosaic patterns of segments with different evolutionary origins. Thus, recombination seems to occur extremely frequent for HSV-1. We conclude by proposing a timescale for HSV-1 evolution, and by discussing putative underlying mechanisms for why these otherwise biologically similar viruses have such striking evolutionary differences.

  10. The effect of UV-B irradiation on secondary epidermal infection of mice with herpes simplex virus type 1

    Energy Technology Data Exchange (ETDEWEB)

    El-Ghorr, A.A.; Norval, Mary [Edinburgh Univ. Medical School (United Kingdom). Dept. of Medical Microbiology

    1996-03-01

    Previous studies have indicated that suberythemal ultraviolet B (UV-B) irradiation of C3H mice before primary infection with herpes simplex virus (HSV) type 1 does not result in increased morbidity or mortality, but a suppressed delayed type hypersensitivity (DH) to the virus can be demonstrated. Any effect of UV radiation on pathogenesis during secondary epidermal HSV infection has not been previously examined. Mice were immunized by subcutaneous injection of inactivated HSV and, 5 days later, one group was UV-B-irradiated. The next day all mice were challenged epidermally with HSV. Most of the mice (92%) in the irradiated group developed severe lesions, whilst 59% of the non-irradiated group had mild lesions and 30% no lesions. Infectious virus was not isolated from the adrenal glands after challenge in either group. In addition, the DH to the virus was not affected by the UV exposure. (author).

  11. Purification of Herpes Simplex Virus Type 1 for Production of High Titer Polyclonal Antibody against the Virus

    Directory of Open Access Journals (Sweden)

    Z Meshkat

    2008-12-01

    Full Text Available ABSTRACT: Introduction & Objective: Herpes simplex virus type 1 infection is one of the most prevalent viral infections worldwide. Different methods are being investigated for the virus’ detection, prevention and therapy. The aim of the present study was to purify the virus and to produce a high titer polyclonal antibody against the virus. Materials & Methods: This experimental study was done in the Virology Department of Tarbiat Modares University from 2001 to 2002. Virus purification was done using serial dilution and plaque purification protocols. A single plaque was chosen and propagated, and the virus titer was determined. In inoculated animals, the titer of produced antibody against the virus was measured by virus neutralization test. Results: Using virus neutralization test, it was found that the high level of antibody has been raised in animals against the virus. Conclusion: Considering the preparation of high titer antibody against the virus, the produced antibody can be used for the development and optimization of different diagnostic methods.

  12. Randomized clinical study comparing Compeed (R) cold sore patch to acyclovir cream 5% in the treatment of herpes simplex labialis

    DEFF Research Database (Denmark)

    Karlsmark, T.; Goodman, J.J.; Drouault, Y.

    2008-01-01

    Background Hydrocolloid technology has been proven effective in treating dermal wounds. A previous study showed that a newly developed thin hydrocolloid patch [Compeed (R) cold sore patch (CSP)] provided multiple wound-healing benefits across all stages of a herpes simplex labialis (HSL) outbreak......) at the onset of symptoms until the lesion healed, for a maximum of 10 days. The primary end point was the subject's global assessment of therapy (SGAT; 0-10 scale; 0 = no response, 10 = excellent response). Multiple secondary end points included clinician-assessed healing time and subject assessment of lesion...... protection, noticeability and social embarrassment. Results CSP and acyclovir were highly effective (mean SGAT = 7.89 and 8.00, respectively), with no significant difference observed (P = 0.65). The difference in healing times between products was not significant (median, 7.57 days with CSP vs. 7.03 days...

  13. Herpes Simplex Virus Type II Infection of Ileum Mesothelium: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    SAC Medlicott

    2005-01-01

    Full Text Available Disseminated herpes simplex virus (HSV infection usually manifests in the immunocompromised. However, anecdotal examples of visceral HSV disease and viremia have complicated type I diabetes. A case of a 53-year-old type I diabetic patient with bowel obstruction one week subsequent to bronchitis is reported. At laparotomy, a perforated segment of ileum was associated with an adhesive peritoneal band. HSV cytopathic atypia and HSV immunohistochemical staining were confined to fibrocytes and mesothelial cells without involvement of the epithelium. Dissemination of symptomatic HSV pneumonia was verified by histology, immunohistochemistry, in situ hybridization, polymerase chain reaction and direct fluorescence antibody. Intravenous acyclovir resolved symptoms. This is a novel documentation of HSV complicating ileal adhesive band disease. Furthermore, this case indicates that the HSV cytopathic effect is not unique to the epithelium. Disseminated infection can manifest in myofibrocytes and mesothelium, distinguishing it from standard epithelial atypia of localized HSV infection.

  14. Role of a cdk5-associated protein, p35, in herpes simplex virus type 1 replication in vivo.

    Science.gov (United States)

    Haenchen, Steve D; Utter, Jeff A; Bayless, Adam M; Dobrowsky, Rick T; Davido, David J

    2010-10-01

    Previous studies have shown that herpes simplex virus type 1 (HSV-1) replication is inhibited by the cyclin-dependent kinase (cdk) inhibitor roscovitine. One roscovitine-sensitive cdk that functions in neurons is cdk5, which is activated in part by its binding partner, p35. Because HSV establishes latent infections in sensory neurons, we sought to determine the role p35 plays in HSV-1 replication in vivo. For these studies, wild-type (wt) and p35−/− mice were infected with HSV-1 using the mouse ocular model of HSV latency and reactivation. The current results indicate that p35 is an important determinant of viral replication in vivo.

  15. Effect of ammonium chloride and tunicamycin on the glycoprotein content and infectivity of herpes simplex virus type 1

    Energy Technology Data Exchange (ETDEWEB)

    Kousoulas, K.G.; Bzik, D.J.; DeLuca, N.; Person, S.

    1983-01-01

    Infectious virions of MP, a syncytial strain of herpes simplex virus type 1, are formed in the presence of 50 mM NH/sub 4/Cl. Underglycosylated virion glycoproteins are synthesized in infected cells and are incorporated into virions in the presence of the same concentration of NH/sub 4/Cl. We conclude that fully glycosylated glycoproteins are not required for viral infectivity. Virus particles, deficient in glycosylated glycoproteins, are assembled in the presence of tunicamycin but they are not infectious. The decrease in infectivity could be due to the decreased amount of the gB or possibly other peptides and/or to the lack of the high-mannose saccharides of precursor glycoproteins. 32 references, 4 figures.

  16. Poor neurological sequelae of herpes simplex virus encephalitis in an infant despite adequate antiviral and adjunct corticosteroid therapy

    Directory of Open Access Journals (Sweden)

    Ratna B Basak

    2011-01-01

    Full Text Available A 2-month-old infant presented to our emergency department with fever, altered consciousness, and focal seizures of acute onset. He had vesicular skin lesions over the right preauricular region. CT brain showed a large hypodense lesion involving the left temporo-parietal region, left basal ganglia and left thalamus. MRI brain revealed bilateral multifocal corticomedullary lesions suggestive of encephalitis. CSF-PCR was positive for herpes simplex virus (HSV type I. He was treated with standard dose intravenous acyclovir for 15 days along with a trial of pulse methylprednisolone, but was readmitted within a week with features of an early relapse. The infant survived but developed significant neurological sequelae. Although treatment of HSV is available, the neurological outcome is guarded even with adequate antiviral therapy. Adjunct corticosteroid therapy did not appear to attenuate the neurological sequelae.

  17. Herpes Simplex Virus Hepatitis: A Presentation of Multi-Institutional Cases to Promote Early Diagnosis and Management of the Disease

    Directory of Open Access Journals (Sweden)

    Ashwinee Natu

    2017-01-01

    Full Text Available Objective. To compare three cases of Herpes simplex virus (HSV hepatitis to increase early diagnosis of the disease. Case  1. A 23-year-old man with Crohn’s disease and oral HSV. HSV hepatitis was diagnosed clinically and he improved with acyclovir. Case  2. An 18-year-old G1P0 woman with transaminitis. Despite early empiric acyclovir therapy, she died due to fulminant liver failure. Case  3. A 65-year-old woman who developed transaminitis after liver transplant. Diagnosis was confirmed by biopsy and she had resolution of acute liver failure with acyclovir. Conclusion. It is imperative that clinicians be aware of patients at high risk for developing HSV hepatitis to increase timely diagnosis and prevent morbidity and fatality.

  18. The identities and anti-herpes simplex virus activity of Clinacanthus nutans and Clinacanthus siamensis

    Institute of Scientific and Technical Information of China (English)

    Paween; Kunsorn; Nijsiri; Ruangrungsi; Vimolmas; Lipipun; Ariya; Khanboon; Kanchana; Rungsihirunrat

    2013-01-01

    Objective:To distinguish the difference among the Clinacanthus nutans(Burm.f.)Lindau(C.nutans)and Clinacanthus siamensis Bremek(C.siamensis)by assessing pharmacognosy characteristics,molecular aspect and also to evaluate their anti-herpes simplex virus(HSV)type 1 and type 2 activities.Methods:Macroscopic and microscopic evaluation were performed according to WHO Geneva guideline.Stomatal number,stomatal index and palisade ratio of leaves were evaluated.Genomic DNA was extracted by modified CTAB method and ITS region was amplified using PGR and then sequenced.Dry leaves were subsequently extracted with n-hexane,dichloromethane and methanol and antiviral activity was performed using plaque reduction assay and the cytotoxicity of the extracts on Vero cells was determined by MTT assay.Results:Cross section of midrib and stem showed similar major components.Leaf measurement index of stomatal number,stomatal index and palisade ratio of C.nutans were 168.32±29.49,13.83±0.86 and 6.84±0.66,respectively,while C.siamensis were 161.60±18.04,11.93±0.81and 3.37±0.31,respectively.The PCR amplification of ITS region generated the PGR product approximately 700 bp in size.There were 34 polymorphisms within the ITS region which consisted of 11 Indels and 23 nucleotide substitutions.The IC50values of C.nutans extracted with n-hexane,dichloromethane and methanol against HSV-1 were(32.05±3.63)μg/mL,(44.50±2.66)μg/mL,(64.93±7.00)μg/mL,respectively where as those of C.siamensis were(60.00±11.61)μg/mL,(55.69+4.41)μg/mL,(37.39±5.85)μg/mL,respectively.Anti HSV-2 activity of n-hexane,dichloromethane and methanol C.nutans leaves extracts were(72.62±12.60)μg/mL,(65.19±21.45)μg/mL,(65.13±2.22)μg/mL,respectively where as those of C.siamensis were(46.52±4.08)μg/mL,(49.63±2.59)μg/mL,(72.64±6.52)μg/mL,respectively.Conclusions:The combination of macroscopic,microscopic and biomolecular method are able to

  19. In vitro study of the effect of a probiotic bacterium Lactobacillus rhamnosus against herpes simplex virus type 1.

    Science.gov (United States)

    Khani, Soghra; Motamedifar, Mohammad; Golmoghaddam, Hossein; Hosseini, Hamideh Mahmoodzadeh; Hashemizadeh, Zahra

    2012-01-01

    Due to the emergence of drug resistance in herpes simplex virus type 1 (HSV-1), researchers are trying to find other methods for treating herpes simplex virus type 1 infections. Probiotic bacteria are effective in macrophage activation and may have antiviral activities. This study aimed at verifying the direct effect of Lactobacillus rhamnosus, a probiotic bacterium, in comparison with Escherichia coli, a non-probiotic one, on HSV-1 infection, and determining its effect on macrophage activation for in vitro elimination of HSV-1 infection. The above bacteria were introduced into HSV-1 infected Vero cells, and their effects were examined using both MTT and plaque assay. To determine macrophage activation against in vitro HSV-1 infection, J774 cells were exposed to these bacteria; then, macrophage viability was examined with the MTT method, and tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and nitric oxide (NO) assessments were performed using the ELISA method. A significant increased viability of macrophages was observed (p Lactobacillus rhamnosus before and after HSV-1 infection when compared with Escherichia coli as a non-probiotic bacterium. However, tumor necrosis factor α concentration produced by Escherichia coli-treated J774 cells was significantly higher than Lactobacillus rhamnosus-treated J774 cells (p Lactobacillus rhamnosus. The results of this study indicate that Lactobacillus rhamnosus enhances macrophage viability for HSV-1 elimination and activation against HSV-1 more effectively, when compared with non-probiotic Escherichia coli. it also seems that receptor occupation of macrophage sites decreases HSV-1 infectivity by both of the studied bacteria.

  20. In vitro antiviral activity of Chamaecrista nictitans (Fabaceae against herpes simplex virus: Biological characterization of mechanisms of action

    Directory of Open Access Journals (Sweden)

    Libia Herrero Uribe

    2004-09-01

    Full Text Available We have previously identified a crude extract of the plant Chamaecrista nictitans (Fabaceaewith antiviral activity against herpes simplex virus.The main objectives of this research were to identify the step of the replication cycle of herpes simplex inhibited by the extract,and to attempt to characterize the chemical characteristics of this extract.The crude extract from Chamaecrista nictitans (Fabaceaewas extracted with a mixture of diclorometane/methanol,and further fractionated following a bioassay-guided protocol using a combination of preparative thin layer and column chromatography.Toxicity and bioassay experiments were carried out in monolayers of Vero cells.The antiviral activity of the extract was assessed by total inhibition of cytopathic effect after three-day incubation.The highest concentration of the extract which was not toxic to the cells was 200 mu g/ml. Western blot and immunofluorescence techniques were used to elucidate the antiviral mechanism of the extract by infecting Vero cells with the virus at different times and monitoring the synthesis of viral proteins.A 60 kDa protein was detected at 2 hr and 8 hr post-infection but no additional proteins were synthesized at later time intervals,and cytopathic effect was not observed after 24 hr.This result indicates that the extract acts at the intracellular level in order to inhibit late transcription.However,it does not inhibit transcription/translation of early viral proteins.These results were confirmed by immunofluorescence experiments.A strong fluorescent signal was observed in control cell monolayers at 24 hr post infection,accompanied with a clear cytopathic effect.In contrast,in the presence of acyclovir or the extract,cells showed very discrete immunofluorescence,characterized by a punctuated pattern, and no cytopathic effect was observed.Neutralization assays were performed using pre-incubation of virus with either specific herpes simplex-1 antiserum,200 mu g/ml of the

  1. Seroprevalence of Herpes Simplex Virus Infection in HIV Coinfected Individuals in Eastern India with Risk Factor Analysis

    Directory of Open Access Journals (Sweden)

    Soumyabrata Nag

    2015-01-01

    Full Text Available Herpes simplex virus type 2 (HSV-2 is the cause of most genital herpes while HSV-1 is responsible for orolabial and facial lesions. In immunocompromised individuals, like HIV patients, impaired immunity leads to more frequent symptomatic and asymptomatic HSV infection. Fifty-two blood samples from HIV patients with clinically diagnosed HSV infection were taken as cases, while 45 blood samples each from HIV-infected (HIV control and noninfected patients without any herpetic lesion (non-HIV control were taken as control. Serum was tested for IgM and IgG antibodies of both HSV-1 and HSV-2 by ELISA. The seroprevalence was compared among the three groups of study population, considering the demographic and socioeconomic parameters. The HSV-2 IgM was significantly higher (p<0.005 in the HIV patient group (34.6% than the HIV control (2.2% and non-HIV control (2.2% groups, whereas HSV-2 IgG seroprevalence was higher in both HIV patient (61.5% and HIV control (57.8% groups than the non-HIV control group (17.8%. The prevalence of HSV-2 was significantly higher in persons with multiple partners and in the reproductive age group. The overall seroprevalence of HSV-1 IgM was too low (<5%, whereas it was too high (about 90% with HSV-1 IgG in all three study groups.

  2. Prevalence of specific herpes simplex virus-2 antibodies and associated factors in women of a rural town of Colombia.

    Science.gov (United States)

    Sierra, Clara A; Bedoya, Astrid M; Paris, Sara; Baena, Armando; Gaviria, Angela M; Rojas, Carlos A; Arbelaez, Maria P; Sanchez, Gloria I

    2011-04-01

    There is lack of age-specific seroprevalence surveys and identification of factors associated with herpes simplex virus type-2 seropositivity (HSV-2) in rural populations in Colombia. A random sample of 869 women was interviewed about socio-demographic aspects, sexual and reproductive history. Antibodies to HSV-2 were determined by a specific type immunoenzymatic technique (ELISA). Participants had a mean age of 38±16.1 years, 67% were married, 60% monogamous and 47% reported use of condoms. HSV-2 seroprevalence was 19.1% (95% CI: 16.6-21.9) and it was strongly associated with increasing age (Ptrend31 years of sexual activity with regular or occasional sexual partners (OR=4.3; 95% CI: 1.2-15.7) and not using condoms with regular sexual partners (OR=2.1; 95% CI: 1.4-3.3) were more likely to be HSV-2 seropositive. The overall seroprevalence rate of women of Pueblorrico, Colombia, is lower than that reported in other Latin American countries especially in women>45 years. The difference may be explained by higher prevalence of condom use in this population or lower exposure to herpes infection in male as well as females in the past.

  3. Herpes Simplex Virus-2 Glycoprotein Interaction with HVEM Influences Virus-Specific Recall Cellular Responses at the Mucosa

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    Sarah J. Kopp

    2012-01-01

    Full Text Available Infection of susceptible cells by herpes simplex virus (HSV requires the interaction of the HSV gD glycoprotein with one of two principal entry receptors, herpes virus entry mediator (HVEM or nectins. HVEM naturally functions in immune signaling, and the gD-HVEM interaction alters innate signaling early after mucosal infection. We investigated whether the gD-HVEM interaction during priming changes lymphocyte recall responses in the murine intravaginal model. Mice were primed with attenuated HSV-2 expressing wild-type gD or mutant gD unable to engage HVEM and challenged 32 days later with virulent HSV-2 expressing wild-type gD. HSV-specific CD8+ T cells were decreased at the genital mucosa during the recall response after priming with virus unable to engage HVEM but did not differ in draining lymph nodes. CD4+ T cells, which are critical for entry of HSV-specific CD8+ T cells into mucosa in acute infection, did not differ between the two groups in either tissue. An inverse association between Foxp3+ CD4+ regulatory T cells and CD8+ infiltration into the mucosa was not statistically significant. CXCR3 surface expression was not significantly different among different lymphocyte subsets. We conclude that engagement of HVEM during the acute phase of HSV infection influences the antiviral CD8+ recall response by an unexplained mechanism.

  4. Preparation and evaluation of novel in situ gels containing acyclovir for the treatment of oral herpes simplex virus infections.

    Science.gov (United States)

    Chaudhary, Binu; Verma, Surajpal

    2014-01-01

    The objective of this work was to develop an oral mucosal drug delivery system to facilitate the local and systemic delivery of acyclovir for the treatment of oral herpes infection caused by the herpes simplex virus (HSV). An in situ gelling system was used to increase the residence time and thus the bioavailability of acyclovir in oral mucosa. Temperature and pH trigged in situ gel formulations were prepared by cold method using polymers like poloxamer 407, carbopol 934, and HPMC. Glycerin and a mixture of tween 80 and ethanol (1 : 2 ratio) were used as the drug dissolving solvent. The pH of carbopol containing formulation was adjusted to pH 5.8 while the pH of poloxamer solution was adjusted to pH 7. These formulations were evaluated for sol-gel transition temperature, gelling capacity, pH, viscosity, spreadability, gel strength, drug content, ex-vitro permeation, and mucoadhesion. The gelation temperatures of all the formulations were within the range of 28-38°C. All the formulations exhibited fairly uniform drug content (98.15-99.75%). Drug release study of all the formulations showed sustained release properties. The release of drug through these in situ gel formulations followed the Higuchi model and Korsmeyer peppas model mechanism.

  5. Seroprevalence of herpes simplex virus-2 infection among women seeking medical care for signs and symptoms of vaginitis.

    Science.gov (United States)

    Ross, Sharon E; Carter, Belvia; Lambert, Seraphine

    2009-01-01

    Two identically designed studies were conducted to determine the prevalence of herpes simplex virus type 2 (HSV-2) infection and viral shedding among women with no known history of genital herpes or HSV-2 seropositivity, who sought care at a US-based obstetrics/gynaecology clinic because of recurrent signs and symptoms of vaginitis. Samples comprised 50 women of any race (All-Comers Sample; Study 1) and 49 black women (Black Sample; Study 2) diagnosed at the clinic visit with vaginitis on the basis of standard work-up and medical history. In the All-Comers Sample, 15 (30%) women were HSV-2 seropositive and two (4%) were positive for HSV-2 by polymerase chain reaction (PCR); these two patients were also HSV-2 seropositive. Therefore, among patients seropositive for HSV-2, two (13%) were shedding virus at the time of the clinic visit. In the Black Sample, 25 (51%) were HSV-2 seropositive and two (4%) were PCR positive for HSV-2. Factors associated with HSV-2 seropositivity included age >30 years, erythema on pelvic examination, age vaginitis.

  6. Neonatal herpes simplex virus infection following Jewish ritual circumcisions that included direct orogenital suction - New York City, 2000-2011.

    Science.gov (United States)

    2012-06-08

    Herpes simplex virus (HSV) infection commonly causes "cold sores" (HSV type 1 [HSV-1]) and genital herpes (HSV-1 or HSV type 2 [HSV-2]); HSV infection in newborns can result in death or permanent disability. During November 2000-December 2011, a total of 11 newborn males had laboratory-confirmed HSV infection in the weeks following out-of-hospital Jewish ritual circumcision, investigators from the New York City Department of Health and Mental Hygiene (DOHMH) learned. Ten of the 11 newborns were hospitalized; two died. In six of the 11 cases, health-care providers confirmed parental reports that the ritual circumcision included an ultra-Orthodox Jewish practice known as metzitzah b'peh, in which the circumciser (mohel, plural: mohelim) places his mouth directly on the newly circumcised penis and sucks blood away from the circumcision wound (direct orogenital suction). In the remaining cases, other evidence suggested that genital infection was introduced by direct orogenital suction (probable direct orogenital suction). Based on cases reported to DOHMH during April 2006-December 2011, the risk for neonatal herpes caused by HSV-1 and untyped HSV following Jewish ritual circumcision with confirmed or probable direct orogenital suction in New York City was estimated at 1 in 4,098 or 3.4 times greater than the risk among male infants considered unlikely to have had direct orogenital suction. Oral contact with a newborn's open wound risks transmission of HSV and other pathogens. Circumcision is a surgical procedure that should be performed under sterile conditions. Health-care professionals advising parents and parents choosing Jewish ritual circumcision should inquire in advance whether direct orogenital suction will be performed, and orogenital suction should be avoided.

  7. Amino acid substitutions in the thymidine kinase gene of induced acyclovir-resistant herpes simplex virus type 1

    Science.gov (United States)

    Hussin, Ainulkhir; Nor, Norefrina Shafinaz Md; Ibrahim, Nazlina

    2013-11-01

    Acyclovir (ACV) is an antiviral drug of choice in healthcare setting to treat infections caused by herpes viruses, including, but not limited to genital herpes, cold sores, shingles and chicken pox. Acyclovir resistance has emerged significantly due to extensive use and misuse of this antiviral in human, especially in immunocompromised patients. However, it remains unclear about the amino acid substitutions in thymidine (TK) gene, which specifically confer the resistance-associated mutation in herpes simplex virus. Hence, acyclovir-resistant HSV-1 was selected at high concentration (2.0 - 4.5 μg/mL), and the TK-gene was subjected to sequencing and genotypic characterization. Genotypic sequences comparison was done using HSV-1 17 (GenBank Accesion no. X14112) for resistance-associated mutation determination whereas HSV-1 KOS, HSV-1 473/08 and HSV clinical isolates sequences were used for polymorphism-associated mutation. The result showed that amino acid substitutions at the non-conserved region (UKM-1: Gln34Lys, UKM-2: Arg32Ser & UKM-5: Arg32Cys) and ATP-binding site (UKM-3: Tyr53End & UKM-4: Ile54Leu) of the TK-gene. These discoveries play an important role to extend another dimension to the evolution of acyclovir-resistant HSV-1 and suggest that selection at high ACV concentration induced ACV-resistant HSV-1 evolution. These findings also expand the knowledge on the type of mutations among acyclovir-resistant HSV-1. In conclusion, HSV-1 showed multiple strategies to exhibit acyclovir resistance, including amino acid substitutions in the TK gene.

  8. Analysis of colorectal cancer and polyp for presence herpes simplex virus and cytomegalovirus DNA sequences by polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Sahar Mehrabani khasraghi

    2016-05-01

    Full Text Available Introduction: In recent years, it was demonstrated that there is a clear association between the complicated course of colorectal cancer (CRC and the presence of herpes viruses. Despite a great number of published reports, the exact pathogenic role of herpes viruses remains unclear in these patients. The purpose of this study is to explore the prevalence of herpes simplex virus (HSV and cytomegalovirus (CMV in patients with CRC and polyp in comparison with healthy subjects using the polymerase chain reaction (PCR method. Methods: In this case-control study, 15 biopsies of patients with CRC and 20 colorectal polyp sample were selected. From each patient, two tissue samples were obtained: one sample from malignant tissue, and the other from normal colorectal tissue in an area located 15 cm away from the malignant tissue. Furthermore, 35 samples from healthy people as controls were selected. After DNA extraction, PCR was used to determine HSV and CMV genomes by specific primers. A statistical analysis was performed using the chi-square test. Results: Five CRC patients (33.3% had HSV DNA detected in both the malignant and the matched normal tissue. Five CRC patients (33.3% and seven polyp patients (35.0% had CMV DNA detected in both the malignant and the matched normal tissue. HSV DNA was found in 20% and CMV DNA in 37.1% of samples from healthy people as a control group. Thus, no significant association was observed between the prevalence of HSV and CMV, and an incidence of CRC and polyps according to the location of the samples as compared with the control group. Conclusion: The findings demonstrated that there is no direct molecular evidence to support the association between HSV and CMV and human colorectal malignancies. However, the results from this study do not exclude a possible oncogenic role of these viruses in the neoplastic development of colon cells.

  9. Clinical and virologic response to episodic acyclovir for genital ulcers among HIV-1 seronegative, herpes simplex virus type 2 seropositive African women: a randomized, placebo-controlled trial.

    Science.gov (United States)

    Baeten, Jared M; Reid, Stewart E; Delany-Moretlwe, Sinead; Hughes, James P; Wang, Richard S; Wilcox, Ellen; Limbada, Mohammed; Akpomiemie, Godspower; Corey, Lawrence; Wald, Anna; Celum, Connie

    2012-01-01

    In a randomized trial among African women with recurrent genital herpes, episodic acyclovir therapy resulted in modestly greater likelihood of lesion healing (hazard ratio [HR] = 1.48, P = 0.098; mean, 5.1 vs. 6.0 days) and cessation of herpes simplex virus shedding (HR = 1.88, P = 0.008; mean, 3.0 vs. 5.0 days) compared with placebo, similar to results of studies in high-income countries (ClinicalTrials.gov registration NCT00808405).

  10. Tolerance and immunity in mice infected with herpes simplex virus: simultaneous induction of protective immunity and tolerance to delayed-type hypersensitivity.

    Science.gov (United States)

    Nash, A A; Gell, P G; Wildy, P

    1981-01-01

    Unresponsiveness to delayed type hypersensitivity was induced in mice following an intravenous injection of herpes simplex virus. The principal tolerogens used were thymidine kinase-deficient virus mutants which grow poorly in vivo; u.v.-inactivated and to a lesser extent formalin-inactivated virus were also tolerogenic. The tolerance induced was specific for the virus type. Despite the tolerance to delayed hypersensitivity, anti-viral immunity is present as determined by the rapid inactivation of infectious virus. The mechanism of tolerance to herpes virus and the importance of these observations for the pathogenesis of viral disease is discussed. PMID:7251047

  11. Tolerance and immunity in mice infected with herpes simplex virus: studies on the mechanism of tolerance to delayed-type hypersensitivity.

    Science.gov (United States)

    Nash, A A; Phelan, J; Gell, P G; Wildy, P

    1981-01-01

    Tolerance to delayed-type hypersensitivity is produced in mice following an intravenous injection of herpes simplex virus. This form of tolerance is produced early on, following simultaneous injections of virus subcutaneously and intravenously, and is long lasting (greater than 100 days). The early tolerance mechanism is resistant to high doses of cyclophosphamide and is not transferable by serum or spleen cells taken after 7 days. However, spleen cells taken at 14 days onwards inhibit the induction of delayed hypersensitivity when transferred to normal syngeneic recipients. These cells are T lymphocytes and are specific for the herpes type used in the induction. PMID:6265348

  12. Genital herpes - self-care

    Science.gov (United States)

    Herpes - genital -self-care; Herpes simplex - genital - self-care; Herpesvirus 2 - self-care; HSV-2 - self-care ... genital herpes can be treated. Follow your health care provider's instructions for treatment and follow-up.

  13. Characterization of heterosubunit complexes formed by the R1 and R2 subunits of herpes simplex virus 1 and equine herpes virus 4 ribonucleotide reductase.

    Science.gov (United States)

    Sun, Y; Conner, J

    2000-04-01

    We report on the separate PCR cloning and subsequent expression and purification of the large (R1) and small (R2) subunits from equine herpes virus type 4 (EHV-4) ribonucleotide reductase. The EHV-4 R1 and R2 subunits reconstituted an active enzyme and their abilities to complement the R1 and R2 subunits from the closely related herpes simplex virus 1 (HSV-1) ribonucleotide reductase, with the use of subunit interaction and enzyme activity assays, were analysed. Both EHV-4 R1/HSV-1 R2 and HSV-1 R1/EHV-4 R2 were able to assemble heterosubunit complexes but, surprisingly, neither of these complexes was fully active in enzyme activity assays; the EHV-4 R1/HSV-1 R2 and HSV-1 R1/EHV-4 R2 enzymes had 50% and 5% of their respective wild-type activities. Site-directed mutagenesis was used to alter two non-conserved residues located within the highly conserved and functionally important C-termini of the EHV-4 and HSV-1 R1 proteins. Mutation of Pro-737 to Lys and Lys-1084 to Pro in EHV-4 and HSV-1 R1 respectively had no effects on subunit assembly. Mutation of Pro-737 to Lys in EHV-4 R1 decreased enzyme activity by 50%; replacement of Lys-1084 by Pro in HSV-1 R1 had no effect on enzyme activity. Both alterations failed to restore full enzyme activities to the heterosubunit enzymes. Therefore probably neither of these amino acids has a direct role in catalysis. However, mutation of the highly conserved Tyr-1111 to Phe in HSV-1 R1 inactivated enzyme activity without affecting subunit interaction.

  14. Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis

    Science.gov (United States)

    Jones, Clinton

    2013-01-01

    α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts. PMID:25278776

  15. Antiviral and virucidal activity of Chelidonium majus L. extract compared with Acyclovir against Herpes simplex virus type 1

    Directory of Open Access Journals (Sweden)

    M Sadeghpour Natanzi

    2017-02-01

    Full Text Available Background and aim: Herpes simplex virus is one of the most important human pathogenic viruses that may lead to oral herpes, keratoconjunctivitis and even encephalitis. A number of enzymes of the virus such as DNA polymerase can be targeted antiviral drugs. Acyclovir is used to treat infections of the virus, today due to drug resistance, need to do more research on finding new drugs, especially herbal medicines has increased. This study aimed to investigate the antiviral effect of methanol extract of Chelidonium majus compared with acyclovir against the virus in HeLa cell culture. Methods: In this experimental study, the toxicity of Chelidonium majus L. methanol extract and acyclovir on HeLa cell was determined with both MTT and Trypan blue methods. The antiviral effect of Chelidonium majus L. extract and acyclovir was evaluated in different concentration (1800- 1700- 1600- 1500- 1400 and 500- 100- 75- 50- 30-10 µg/ml and also in different times before, after and during of virus adsorption respectively.  The virus titer was measured by tissue culture infectious dose 50 TCID50(  method. The T-test method was used to comparing the effects of both compounds on virus. Results: The maximum non-toxic concentration of Chelidonium majus L. extract on HeLa cell was determined 1600 µg/ml that has the maximum inhibitory effect on HSV-1 replication. Acyclovir was shown low toxicity on HeLa cells.The 30 µg/ml concentration of acyclovir was considered for the next steps of the study.The highest inhibitory effect of the extract was observed 1 hour after absorption and the virus replication was suppressed completely by the acyclovir immediately after virus adsorption up to 8 hours after infection. Conclusion: The Chelidonium majus L. methanol extract has less effect than the acyclovir on inhibition of herpes simplex virus replication in a first few hours of infection. More research is needed to achieve effective compounds with antiviral activity of above

  16. Genital herpes

    Science.gov (United States)

    ... In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious ... JT and Corey L. Herpes simplex virus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, ...

  17. The calcitonin receptor gene is a candidate for regulation of susceptibility to herpes simplex type 1 neuronal infection leading to encephalitis in rat.

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    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a fatal infection of the central nervous system (CNS predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL, Hse1, on rat chromosome 4 (confidence interval 24.3-31 Mb; LOD score 29.5 governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development.

  18. The interaction between herpes simplex virus 1 genome and promyelocytic leukemia nuclear bodies (PML-NBs as a hallmark of the entry in latency

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    Patrick Lomonte

    2016-11-01

    Full Text Available Herpes simplex virus 1 (HSV-1 is a human pathogen that establishes latency in the nucleus of infected neurons in the PNS and the CNS. At the transcriptional level latency is characterized by a quasi-complete silencing of the extrachromosomal viral genome that otherwise expresses more than 80 genes during the lytic cycle. In neurons, latency is anticipated to be the default transcriptional program; however, limited information exists on the molecular mechanisms that force the virus to enter the latent state. Our recent study demonstrates that the interaction of the viral genomes with the nuclear architecture and specifically the promyelocytic leukemia nuclear bodies (PML-NBs is a major determinant for the entry of HSV-1 into latency (Maroui MA, Callé A et al. (2016. Latency entry of herpes simplex virus 1 is determined by the interaction of its genome with the nuclear environment. PLoS Pathogens 12(9: e1005834..

  19. PREVALENCE OF HERPES SIMPLEX VIRUS TYPES 1 AND 2 AND ASSOCIATED SOCIODEMOGRAPHIC VARIABLES IN PREGNANT WOMEN ATTENDING KING FAHD HOSPITAL OF THE UNIVERSITY

    OpenAIRE

    Obeid, Obeid E.

    2007-01-01

    Objectives: The risk factors associated with herpes simplex virus (HSV) seropositivity in pregnant women in Saudi Arabia are not known. This study was aimed at identifying the sociodemographic variables associated with seroprevalence of HSV-1 and HSV-2 in pregnant women in a Saudi hospital. Materials and Methods: This is a hospital-based cross-sectional study that included all pregnant mothers who delivered at King Fahd Hospital of the University (KFHU) over a period of two years (Novembe...

  20. Interaction of herpes simplex virus type 2 (HSV-2) glycoprotein D with the host cell surface is sufficient to induce Chlamydia trachomatis persistence

    OpenAIRE

    Vanover, J.; Kintner, J.; Whittimore, J.; Schoborg, R. V.

    2010-01-01

    When presented with certain unfavourable environmental conditions, Chlamydia trachomatis reticulate bodies (RBs) enter into a viable, yet non-cultivable state called persistence. Previously, we established an in vitro C. trachomatis and herpes simplex virus type 2 (HSV-2) co-infection model. These data indicate that (i) viral co-infection stimulates chlamydial persistence, (ii) productive HSV replication is not required for persistence induction, and (iii) HSV-induced persistence is not media...

  1. Use of a fragment of glycoprotein G-2 produced in the baculovirus expression system for detecting herpes simplex virus type 2-specific antibodies

    NARCIS (Netherlands)

    Ikoma, M; Liljeqvist, JA; Glazenburg, KL; The, TH; Welling-Wester, S; Groen, J.

    2002-01-01

    Fragments of glycoprotein G (gG-2(281-594His)), comprising residues 281 to 594 of herpes simplex virus type 2 (HSV-2), glycoprotein G of HSV-1 (gG-1(t26-189His)), and glycoprotein D of HSV-1 (gD-1(1-313)), were expressed in the baculovirus expression system to develop an assay for the detection of H

  2. Synergistic effect of flavones and flavonols against herpes simplex virus type 1 in cell culture. Comparison with the antiviral activity of propolis.

    Science.gov (United States)

    Amoros, M; Simões, C M; Girre, L; Sauvager, F; Cormier, M

    1992-12-01

    The in vitro activity against herpes simplex virus type 1 of the major flavonoids identified in propolis was investigated. Flavonols were found to be more active than flavones, the order of importance being galangin, kaempferol, and quercetin. The efficacy against HSV-1 of binary flavone-flavonol combinations has been also investigated. The synergy demonstrated by all combinations could explain why propolis is more active than its individual compounds.

  3. Use of a fragment of glycoprotein G-2 produced in the baculovirus expression system for detecting herpes simplex virus type 2-specific antibodies

    NARCIS (Netherlands)

    Ikoma, M; Liljeqvist, JA; Glazenburg, KL; The, TH; Welling-Wester, S; Groen, J.

    Fragments of glycoprotein G (gG-2(281-594His)), comprising residues 281 to 594 of herpes simplex virus type 2 (HSV-2), glycoprotein G of HSV-1 (gG-1(t26-189His)), and glycoprotein D of HSV-1 (gD-1(1-313)), were expressed in the baculovirus expression system to develop an assay for the detection of

  4. Role of Autoantibodies to N-Methyl-d-Aspartate (NMDA) Receptor in Relapsing Herpes Simplex Encephalitis: A Retrospective, One-Center Experience.

    Science.gov (United States)

    Sutcu, Murat; Akturk, Hacer; Somer, Ayper; Tatli, Burak; Torun, Selda Hancerli; Yıldız, Edibe Pembegul; Şık, Guntulu; Citak, Agop; Agacfidan, Ali; Salman, Nuran

    2016-03-01

    Post-herpes simplex virus encephalitis relapses have been recently associated with autoimmunity driven by autoantibodies against N-methyl-d-aspartate (NMDA) receptors. Because it offers different treatment options, determination of this condition is important. Between 2011 and 2014, 7 children with proven diagnosis of herpes simplex virus encephalitis were identified in a university hospital of Istanbul. Two patients had neurologic relapse characterized mainly by movement disorders 2 to 3 weeks after initial encephalitis. The first patient received a second 14 days of acyclovir treatment together with antiepileptic drugs and left with severe neurologic sequelae. The second patient was found to be NMDA receptors antibody positive in the cerebrospinal fluid. She was treated with intravenous immunoglobulin and prednisolone. She showed substantial improvement, gradually regaining lost neurologic abilities. Post-herpes simplex virus encephalitis relapses may frequently be immune-mediated rather than a viral reactivation, particularly in children displaying movement disorders like choreoathetosis. Immunotherapy may provide benefit for this potentially devastating condition, like the case described in this report.

  5. Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii.

    Science.gov (United States)

    Carter, C J

    2009-11-01

    Many genes implicated in schizophrenia can be related to glutamatergic transmission and neuroplasticity, oligodendrocyte function, and other families clearly related to neurobiology and schizophrenia phenotypes. Others appear rather to be involved in the life cycles of the pathogens implicated in the disease. For example, aspartylglucosaminidase (AGA), PLA2, SIAT8B, GALNT7, or B3GAT1 metabolize chemical ligands to which the influenza virus, herpes simplex, cytomegalovirus (CMV), rubella, or Toxoplasma gondii bind. The epidermal growth factor receptor (EGR/EGFR) is used by the CMV to gain entry to cells, and a CMV gene codes for an interleukin (IL-10) mimic that binds the host cognate receptor, IL10R. The fibroblast growth factor receptor (FGFR1) is used by herpes simplex. KPNA3 and RANBP5 control the nuclear import of the influenza virus. Disrupted in schizophrenia 1 (DISC1) controls the microtubule network that is used by viruses as a route to the nucleus, while DTNBP1, MUTED, and BLOC1S3 regulate endosomal to lysosomal routing that is also important in viral traffic. Neuregulin 1 activates ERBB receptors releasing a factor, EBP1, known to inhibit the influenza virus transcriptase. Other viral or bacterial components bind to genes or proteins encoded by CALR, FEZ1, FYN, HSPA1B, IL2, HTR2A, KPNA3, MED12, MED15, MICB, NQO2, PAX6, PIK3C3, RANBP5, or TP53, while the cerebral infectivity of the herpes simplex virus is modified by Apolipoprotein E (APOE). Genes encoding for proteins related to the innate immune response, including cytokine related (CCR5, CSF2RA, CSF2RB, IL1B, IL1RN, IL2, IL3, IL3RA, IL4, IL10, IL10RA, IL18RAP, lymphotoxin-alpha, tumor necrosis factor alpha [TNF]), human leukocyte antigen (HLA) antigens (HLA-A10, HLA-B, HLA-DRB1), and genes involved in antigen processing (angiotensin-converting enzyme and tripeptidyl peptidase 2) are all concerned with defense against invading pathogens. Human microRNAs (Hsa-mir-198 and Hsa-mir-206) are predicted to bind

  6. Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo

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    Yin L

    2017-02-01

    Full Text Available Lei Yin,1–3 Chunhong Zhao,3 Jixia Han,4 Zengjun Li,2 Yanan Zhen,3 Ruixue Xiao,3 Zhongfa Xu,3 Yanlai Sun2 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, 2Department of Gastrointestinal Cancer Surgery, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, 3Department of Gastrointestinal Surgery, The Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, 4Department of General Surgery, The Sixth People’s Hospital of Jinan, Jinan, People’s Republic of China Background: The incidence of colorectal cancer (CRC is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2 in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor.Materials and methods: We investigated the cytopathic effects of oHSV2 in CRC cell lines using the MTT assay. Then, cell cycle progression and apoptosis of oHSV2 were examined by flow cytometry. We generated a model of CRC with mouse CRC cell CT26 in BALB/c mice. The antitumor effects and adaptive immune response of oHSV2 were assessed in tumor-bearing mice. The therapeutic efficacy of oHSV2 was compared with the traditional chemotherapeutic agent, 5-fluorouracil.Results: The in vitro data showed that oHSV2 infected the CRC cell lines successfully and that the tumor cells formed a significant number of syncytiae postinfection. The oHSV2 killed cancer cells independent of the cell cycle and mainly caused tumor cells necrosis. The in vivo results showed that oHSV2 significantly inhibited tumor growth and prolonged survival of

  7. Immune- and Nonimmune-Compartment-Specific Interferon Responses Are Critical Determinants of Herpes Simplex Virus-Induced Generalized Infections and Acute Liver Failure.

    Science.gov (United States)

    Parker, Zachary M; Pasieka, Tracy Jo; Parker, George A; Leib, David A

    2016-12-01

    The interferon (IFN) response to viral pathogens is critical for host survival. In humans and mouse models, defects in IFN responses can result in lethal herpes simplex virus 1 (HSV-1) infections, usually from encephalitis. Although rare, HSV-1 can also cause fulminant hepatic failure, which is often fatal. Although herpes simplex encephalitis has been extensively studied, HSV-1 generalized infections and subsequent acute liver failure are less well understood. We previously demonstrated that IFN-αβγR(-/-) mice are exquisitely susceptible to liver infection following corneal infection with HSV-1. In this study, we used bone marrow chimeras of IFN-αβγR(-/-) (AG129) and wild-type (WT; 129SvEv) mice to probe the underlying IFN-dependent mechanisms that control HSV-1 pathogenesis. After infection, WT mice with either IFN-αβγR(-/-) or WT marrow exhibited comparable survival, while IFN-αβγR(-/-) mice with WT marrow had a significant survival advantage over their counterparts with IFN-αβγR(-/-) marrow. Furthermore, using bioluminescent imaging to maximize data acquisition, we showed that the transfer of IFN-competent hematopoietic cells controlled HSV-1 replication and damage in the livers of IFN-αβγR(-/-) mice. Consistent with this, the inability of IFN-αβγR(-/-) immune cells to control liver infection in IFN-αβγR(-/-) mice manifested as profoundly elevated aspartate transaminase (AST) and alanine transaminase (ALT) levels, indicative of severe liver damage. In contrast, IFN-αβγR(-/-) mice receiving WT marrow exhibited only modest elevations of AST and ALT levels. These studies indicate that IFN responsiveness of the immune system is a major determinant of viral tropism and damage during visceral HSV infections. Herpes simplex virus 1 (HSV-1) infection is an incurable viral infection with the most significant morbidity and mortality occurring in neonates and patients with compromised immune systems. Severe pathologies from HSV include the

  8. Anti-herpes simplex virus activities of monogalactosyl diglyceride and digalactosyl diglyceride from Clinacanthus nutans, a traditional Thai herbal medicine

    Institute of Scientific and Technical Information of China (English)

    Sirada Pongmuangmul; Supaporn Phumiamorn; Phanchana Sanguansermsri; Nalin Wongkattiya; Ian Hamilton Fraser; Donruedee Sanguansermsri

    2016-01-01

    Objective: To evaluate the monogalactosyl diglyceride(MGDG) and digalactosyl diglyceride(DGDG) from Clinacanthus nutans(C. nutans) for their in vitro antiviral activities against herpes simplex virus type 1(HSV-1) and type 2(HSV-2) by plaque reduction assay.Methods: MGDG and DGDG were extracted with chloroform from C. nutans leaves.MGDG and DGDG were separated from chloroform crude extract using column chromatography, characterized by thin layer chromatography and quantified by high performance liquid chromatography. The anti HSV-1 and 2 activity against pre-treatment and posttreatment of the compounds was evaluated using plaque reduction assay. The cytotoxicity of the extract and the compounds on Vero cells were performed by MTT assay.Results: MGDG and DGDG obtained by column chromatography showed identical profiles as standard MGDG and standard DGDG using thin layer chromatography and high performance liquid chromatography. MGDG and DGDG from C. nutans showed 100%inhibition of HSV-1 replication at the post step of infection at noncytotoxic concentration with IC50 values of 36.00 and 40.00 mg/m L, and HSV-2 at 41.00 and 43.20 mg/mL,respectively. Moreover, MGDG and DGDG from C. nutans were demonstrated to have antiherpes simplex activity at the same level as standard synthetic compounds. In contrast, pretreatment of Vero cells with MGDG and DGDG before HSV-1 and HSV-2 infection did not show inhibitory effect against these viruses. MGDG and DGDG exhibited antiviral activity against HSV-1 with selectivity index of 26.00 and 23.00 and HSV-2 of 23.30 and 21.30.Conclusions: MGDG and DGDG from C. nutans, a traditional Thai herbal medicine illustrated inhibitory activity against HSV-1 and HSV-2, probably by inhibiting the late stage of multiplication, suggesting their promising use as anti-HSV agents.

  9. β-Amyloid peptides display protective activity against the human Alzheimer's disease-associated herpes simplex virus-1.

    Science.gov (United States)

    Bourgade, Karine; Garneau, Hugo; Giroux, Geneviève; Le Page, Aurélie Y; Bocti, Christian; Dupuis, Gilles; Frost, Eric H; Fülöp, Tamàs

    2015-02-01

    Amyloid plaques, the hallmark of Alzheimer's disease (AD), contain fibrillar β-amyloid (Aβ) 1-40 and 1-42 peptides. Herpes simplex virus 1 (HSV-1) has been implicated as a risk factor for AD and found to co-localize within amyloid plaques. Aβ 1-40 and Aβ 1-42 display anti-bacterial, anti-yeast and anti-viral activities. Here, fibroblast, epithelial and neuronal cell lines were exposed to Aβ 1-40 or Aβ 1-42 and challenged with HSV-1. Quantitative analysis revealed that Aβ 1-40 and Aβ 1-42 inhibited HSV-1 replication when added 2 h prior to or concomitantly with virus challenge, but not when added 2 or 6 h after virus addition. In contrast, Aβ 1-40 and Aβ 1-42 did not prevent replication of the non-enveloped human adenovirus. In comparison, antimicrobial peptide LL-37 prevented HSV-1 infection independently of its sequence of addition. Our findings showed also that Aβ 1-40 and Aβ 1-42 acted directly on HSV-1 in a cell-free system and prevented viral entry into cells. The sequence homology between Aβ and a proximal transmembrane region of HSV-1 glycoprotein B suggested that Aβ interference with HSV-1 replication could involve its insertion into the HSV-1 envelope. Our data suggest that Aβ peptides represent a novel class of antimicrobial peptides that protect against neurotropic enveloped virus infections such as HSV-1. Overproduction of Aβ peptide to protect against latent herpes viruses and eventually against other infections, may contribute to amyloid plaque formation, and partially explain why brain infections play a pathogenic role in the progression of the sporadic form of AD.

  10. DO HERPES SIMPLEX VIRUSES (TYPE 1 AND 2 PLAY A ROLE IN THE PATHOGENESIS OF HASHIMOTO'S THYROIDITIS?

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    MAZIN J. MOUSA

    2013-01-01

    Full Text Available Objective: Autoimmune thyroid disease is a complex disease with genetic, endogenous and environmental etiologies. This review examines the data related to the role of viruses in the development of Hashimoto's thyroiditis.Materials and methods: This study was conducted on Hashimoto's thyroiditis patients, whom diagnosis was confirmed by testing their post-thyroidectomy specimens histopathologically, along with hormonal assays for their T3, T4 and TSH. The study samples were collected randomly from different hospitals in Al-Hilla City, Babylon-Iraq; during the period from August 2011 to December 2012. The study included 28 patients; 27 of them were females with only one male. Patients' ages ranged from 22 to 51 years, with a mean age of 36.82±7.703 years. A blood samples were drawn from all the above mentioned patients to detect a herpes simplex virus (Type 1 and 2 (HSV 1 and 2 infections and the diagnosis was established by testing the patients' sera with a virus-specific IgM and IgG antibodies using ELISA technique.Results: This study demonstrated an abundant negative result (92.8% for HSV 1-specific IgG among the patients; with equal negative and positive antibody titres for HSV 1-specific IgM. On the other hand; the data concerning HSV 2 showed a complete negativity in IgG specific for the virus among the study patients with plentiful negativity (96.4% regarding the titre of HSV 2-specific IgM.Conclusion: The possible role of human herpes viruses in the pathogenesis of Hashimoto's thyroiditis is not supported by our study; hence our raised question stays open for more investigation on more patients and in different regions of the country, in order to develop new strategies for prevention and/or treatment.

  11. Clinical course and spectrum of intensive care unit patients reactivating herpes simplex-1 virus: A retrospective analysis

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    Sundar Krishna

    2008-01-01

    Full Text Available Background : Herpes simplex-1 virus (HSV-1 reactivation in the respiratory tract is common in intensive care unit (ICU patients. However, susceptible ICU populations are poorly defined. Clinical recognition of HSV infection of the respiratory tract is difficult and the impact of such reactivation is not understood. Materials and Methods : A retrospective analysis of HSV-1 positive patients encountered over a 5-year period at a multispecialty ICU was carried out. HSV-1 was identified in respiratory secretions using a qualitative polymerase chain reaction (PCR technique. Patient charts were reviewed for clinical features that would typify HSV-1 respiratory involvement, and the morbidity and mortality risks found with HSV-1 respiratory involvement. Results : A review of 48 HSV-1 positive ICU patients showed that patients reactivating HSV in the respiratory tract fell into one of the three categories: (1 septic elderly patients with and without ARDS, (2 immunosuppressed patients, especially those receiving high-dose steroids, and (3 post-thoracotomy patients. Abnormalities suggestive of HSV-1 reactivation in the respiratory tract included, haemorrhagic or excessive respiratory secretions, concomitant orofacial herpes (42%, and bronchoscopic abnormalities (hemorrhagic ulcers and mucosal friability (83%. Twenty eight percent of the HSV-1 infected patients experienced postextubation stridor. HSV-1 reactivation was associated with extended ventilator stays, significant mortality (42%, and ventilator-associated pneumonias (52%. Conclusions : Identification of susceptible populations and definition of clinical features of HSV-1 related respiratory disease can enable diagnosis of HSV-1 infection in ICU patients. Although detection by a PCR technique can rapidly diagnose HSV-1 reactivation, prospective studies are required to clarify HSV disease versus mere shedding, and understand the impact of HSV-1 reactivation in hospitalized patients.

  12. HERPES SIMPLEX VIRUS TYPE 2 SEROPOSITIVITY AMONG EVER MARRIED WOMEN IN SOUTH AND NORTH VIETNAM: A POPULATION-BASED STUDY

    Science.gov (United States)

    Van Le, Hoa; Schoenbach, Victor J; Herrero, Rolando; Pham, Anh Thi Hoang; Nguyen, Hieu Trong; Nguyen, Thuy Thi; Muñoz, Nubia; Franceschi, Silvia; Vaccarella, Salvatore; Parkin, Max D; Snijders, Peter JF; Ashley, Rhoda; Smith, Jennifer S

    2010-01-01

    Objective To investigate herpes simplex virus type–2 (HSV-2) seropositivity and associated risk factors in Vietnamese women. Methods Cross-sectional study with personal interviews and gynecological examinations among population-based samples of ever married women, aged 15–69 years, living in Ho Chi Minh City (HCMC) and Hanoi in 1997. Type-specific IgG antibodies against HSV-2 were detected using HerpeSelect ELISA (Focus Diagnostics). Adjusted prevalence ratios were estimated with log-binomial regression. Results HSV-2 seroprevalence was higher in 1,106 women from HCMC (30.8%, 95% CI: 28.1–33.4, age-standardized to 2000 world standard population) than in 1,170 women from Hanoi (8.8%, 95% CI: 7.1–10.5). In HCMC, HSV-2 seroprevalence was higher for women who were not married, HPV DNA positive, current hormonal contraceptive users, or had a history of multiple sexual partners or spontaneous abortion. HCMC seroprevalence was inversely associated with educational attainment, age at first intercourse, and age at first pregnancy. In the multivariable model for HCMC, a trend of increasing HSV-2 seroprevalence with age was observed, and prevalence ratios were nearly identical to age-adjusted prevalence ratios for marital status, age at first pregnancy, and HPV DNA positivity. Conclusion HSV-2 was notably less prevalent in Hanoi than HCMC, where it was associated with traditional HSV-2 risk factors. These results are likely explained by socio-cultural, historical, economic, and demographic factors related to urban-rural and regional differences. Future population-based studies should include men and never-married women as a next step toward obtaining a more nearly complete picture of HSV-2 epidemiology in Vietnam. PMID:19617867

  13. Herpes simplex virus type 2-associated recurrent aseptic (Mollaret's meningitis in genitourinary medicine clinic: a case report

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    Abou-Foul AK

    2014-03-01

    Full Text Available Ahmad K Abou-Foul, Thajunisha M Buhary, Sedki L Gayed Department of Genitourinary Medicine, Royal Blackburn Hospital, East Lancashire Hospitals NHS Trust, Blackburn, UK Introduction: Cases of idiopathic recurrent benign aseptic meningitis were first described by Mollaret. Today, herpes simplex virus (HSV is considered the cause of most cases of Mollaret's meningitis. Case report: A 40-year-old male was referred to our genitourinary medicine clinic with recurrent genital herpetic lesions. He had HSV-2-positive genital ulcers 8 years earlier. One year after the first infection, he developed severe recurrent attacks of headache associated with meningitis symptoms. The results of all radiological and biochemical tests were normal, but the patient reported a correlation between his attacks and genital herpes flare-ups. We diagnosed the patient with Mollaret's meningitis and started him on continuous suppressive acyclovir therapy, which resulted in marked clinical improvement. Discussion: Mollaret's meningitis is a rare form of idiopathic recurrent aseptic meningitis that has a sudden onset, short duration, and spontaneous remission with unpredictable recurrence. We believe that the presence of concurrent or recurrent mucocutaneous herpetic lesions can aid its diagnosis, prior to which, affected patients usually have many unnecessary investigations and treatments. Therefore, detailed sexual history should be sought in all patients with aseptic meningitis, and clinicians should also ask about history of recurrent headaches in all patients with recurrent herpetic anogenital lesions. Continuous suppressive acyclovir therapy may reduce the frequency and severity of attacks and can dramatically improve lifestyle. Keywords: HSV-2 virus, acyclovir, Mollaret's meningitis, recurrent aseptic meningitis, HSV-2 virus, viral meningitis, acyclovir

  14. Cost-effective and label-free holographic biosensor for detection of herpes simplex virus (Conference Presentation)

    Science.gov (United States)

    Ray, Aniruddha; Ho, Ha; Daloglu, Mustafa; Torres, Avee; McLeod, Euan; Ozcan, Aydogan

    2017-03-01

    Herpes is one of the most widespread sexually transmitted viral diseases. Timely detection of Herpes Simplex Virus (HSV) can help prevent the rampant spreading of the virus. Current detection techniques such as viral culture, immuno-assays or Polymerase-Chain-Reaction, are time extensive and require expert handling. Here we present a field-portable, easy-to-use, and cost-effective biosensor for the detection of HSV based on holographic imaging. The virus is first captured from a target solution onto specifically developed substrates, prepared by coating glass coverslips with HSV-specific antibodies, and imaged using a lensfree holographic microscope. Several light-emitting-diodes (LEDs), coupled to multi-mode optical-fibers, are used to illuminate the sample containing the viruses. A micro-controller is used to activate the LEDs one at a time and in-line holograms are recorded using a CMOS imager placed immediately above the substrate. These sub-pixel shifted holograms are used to generate a super-resolved hologram, which is reconstructed to obtain the phase and amplitude images of the viruses. The signal of the viruses is enhanced using self-assembled PEG-based nanolenses, formed around the viral particles. Based on the phase information of the reconstructed images we can estimate the size of the viral particles, with an accuracy of +/- 11 nm, as well as quantify the viral load. The limit-of-detection of this system is estimated to be <500 viral copies per 100 μL sample volume that is imaged over 30 mm^2 field-of-view. This holographic microscopy based biosensor is label-free, cost-effective and field-portable, providing results in 2 hours, including sample preparation and imaging time.

  15. Histone Deacetylase Inhibitors Reduce the Number of Herpes Simplex Virus-1 Genomes Initiating Expression in Individual Cells

    Science.gov (United States)

    Shapira, Lev; Ralph, Maya; Tomer, Enosh; Cohen, Shai; Kobiler, Oren

    2016-01-01

    Although many viral particles can enter a single cell, the number of viral genomes per cell that establish infection is limited. However, mechanisms underlying this restriction were not explored in depth. For herpesviruses, one of the possible mechanisms suggested is chromatinization and silencing of the incoming genomes. To test this hypothesis, we followed infection with three herpes simplex virus 1 (HSV-1) fluorescence expressing recombinants in the presence or absence of histone deacetylases inhibitors (HDACi’s). Unexpectedly, a lower number of viral genomes initiated expression in the presence of these inhibitors. This phenomenon was observed using several HDACi: Trichostatin A (TSA), Suberohydroxamic Acid, Valporic Acid, and Suberoylanilide Hydroxamic Acid. We found that HDACi presence did not change the progeny outcome from the infected cells but did alter the kinetic of the gene expression from the viral genomes. Different cell types (HFF, Vero, and U2OS), which vary in their capability to activate intrinsic and innate immunity, show a cell specific basal average number of viral genomes establishing infection. Importantly, in all cell types, treatment with TSA reduced the number of viral genomes. ND10 nuclear bodies are known to interact with the incoming herpes genomes and repress viral replication. The viral immediate early protein, ICP0, is known to disassemble the ND10 bodies and to induce degradation of some of the host proteins in these domains. HDACi treated cells expressed higher levels of some of the host ND10 proteins (promyelocytic leukemia and ATRX), which may explain the lower number of viral genomes initiating expression per cell. Corroborating this hypothesis, infection with three HSV-1 recombinants carrying a deletion in the gene coding for ICP0, show a reduction in the number of genomes being expressed in U2OS cells. We suggest that alterations in the levels of host proteins involved in intrinsic antiviral defense may result in

  16. Histone deacetylase inhibitors reduce the number of herpes simplex virus-1 genomes initiating expression in individual cells

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    Lev Shapira

    2016-12-01

    Full Text Available Although many viral particles can enter a single cell, the number of viral genomes per cell that establish infection is limited. However, mechanisms underlying this restriction were not explored in depth. For herpesviruses, one of the possible mechanisms suggested is chromatinization and silencing of the incoming genomes. To test this hypothesis, we followed infection with three herpes simplex virus 1 (HSV-1 fluorescence-expressing recombinants in the presence or absence of histone deacetylases inhibitors (HDACi’s. Unexpectedly, a lower number of viral genomes initiated expression in the presence of these inhibitors. This phenomenon was observed using several HDACi: Trichostatin A (TSA, Suberohydroxamic Acid (SBX, Valporic Acid (VPA and Suberoylanilide Hydoxamic Acid (SAHA. We found that HDACi presence did not change the progeny outcome from the infected cells but did alter the kinetic of the gene expression from the viral genomes. Different cell types (HFF, Vero and U2OS, which vary in their capability to activate intrinsic and innate immunity, show a cell specific basal average number of viral genomes establishing infection. Importantly, in all cell types, treatment with TSA reduced the number of viral genomes. ND10 nuclear bodies are known to interact with the incoming herpes genomes and repress viral replication. The viral immediate early protein, ICP0, is known to disassemble the ND10 bodies and to induce degradation of some of the host proteins in these domains. HDACi treated cells expressed higher levels of some of the host ND10 proteins (PML and ATRX, which may explain the lower number of viral genomes initiating expression per cell. Corroborating this hypothesis, infection with three HSV-1 recombinants carrying a deletion in the gene coding for ICP0, show a reduction in the number of genomes being expressed in U2OS cells. We suggest that alterations in the levels of host proteins involved in intrinsic antiviral defense may result in

  17. Herpes simples no serviço de estomatologia do Hospital São Lucas da PUCRS: estudo epidemiológico =Herpes simplex at stomatology division of Hospital São Lucas, PUCRS: epidemiological study

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    Stemmer, Ana Carolina et al.

    2005-01-01

    Full Text Available O presente estudo teve por objetivo investigar o perfil epidemiológico do herpes simples entre os pacientes do Serviço de Estomatologia do Hospital São Lucas da PUCRS. Foram analisados 167 prontuários dos quais 98 (58,68% tiveram diagnóstico de gengivoestomatite herpética primária e 69 (41,32% de herpes recorrente. As variáveis idade e sexo dos pacientes, sintomas da manifestação herpética, sítios anatômicos afetados, linfadenopatia e complicações, bem como tratamento empregado foram analisadas. Na gengivoestomatite herpética, 69,38% tinham entre 21 e 40 anos. O sexo feminino foi o mais acometido tanto pela doença primária quanto pela recorrente. Entre os sítios da cavidade bucal destacaram-se língua e gengiva para a doença primária, e o vermelhão dos lábios para a secundária. Os sintomas mais freqüentes da primoinfecção foram febre e dor, já nas lesões recorrentes, destacaram-se dor e ardência. Todos os pacientes exibiram linfadenopatia. Analgésicos e antitérmicos foram as principais drogas no tratamento da gengiovoestomatite herpética primária, enquanto, para o herpes recorrente, foram os anti-sépticos e antivirais. The aim of this work was to investigate the epidemiological profile of Herpes simplex at Stomatology Division of Hospital São Lucas-PUCRS. Records of 167 patients were reviewed: 98 (58,68% of them were primary herpetic gingivostomatitis patients and 69 (41,32% were recurrent herpes patients. Age, sex, symptoms, anatomical sites affected, complications, lymphadenopathy and treatment were analyzed. Results showed that 69,38% of primary herpetic gingivostomatitis patients were under age of 21 years, while 41,42% of recurrent herpes patients were between 21 and 40 years of age. Females were more affected than males by both primary and secondary disease. The most commonly involved anatomical sites were tongue and gums in primary herpetic gingivostomatitis and lip vermilion in recurrent herpes. Fever

  18. Leflunomide in the Treatment of a Pseudotumoral Genital Herpes Simplex Virus Infection in an HIV Patient

    OpenAIRE

    Marie R. Roger; Anstead, Gregory M.

    2017-01-01

    The patient is a 52-year-old African American man with a past medical history of HIV infection (on antiretroviral therapy, CD4 count 399 cells/µL, and undetectable HIV viral load) and recurrent genital herpes. While on valacyclovir, the patient presented with four tumorous lesions on the perineum and scrotum. A biopsy specimen stained positively with HSV-1 and HSV-2 immunostains and displayed a lymphoplasmacytic infiltrate. The patient received foscarnet and imiquimod for two weeks with minim...

  19. A strategy for O-glycoproteomics of enveloped viruses--the O-glycoproteome of herpes simplex virus type 1.

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    Ieva Bagdonaite

    2015-04-01

    Full Text Available Glycosylation of viral envelope proteins is important for infectivity and interaction with host immunity, however, our current knowledge of the functions of glycosylation is largely limited to N-glycosylation because it is difficult to predict and identify site-specific O-glycosylation. Here, we present a novel proteome-wide discovery strategy for O-glycosylation sites on viral envelope proteins using herpes simplex virus type 1 (HSV-1 as a model. We identified 74 O-linked glycosylation sites on 8 out of the 12 HSV-1 envelope proteins. Two of the identified glycosites found in glycoprotein B were previously implicated in virus attachment to immune cells. We show that HSV-1 infection distorts the secretory pathway and that infected cells accumulate glycoproteins with truncated O-glycans, nonetheless retaining the ability to elongate most of the surface glycans. With the use of precise gene editing, we further demonstrate that elongated O-glycans are essential for HSV-1 in human HaCaT keratinocytes, where HSV-1 produced markedly lower viral titers in HaCaT with abrogated O-glycans compared to the isogenic counterpart with normal O-glycans. The roles of O-linked glycosylation for viral entry, formation, secretion, and immune recognition are poorly understood, and the O-glycoproteomics strategy presented here now opens for unbiased discovery on all enveloped viruses.

  20. Doxorubicin-enriched, ALDHbr mouse breast cancer stem cells are treatable to oncolytic herpes simplex virus type 1

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    Zhuang Xiufen

    2012-11-01

    Full Text Available Abstract Background The primary objective of this study was to test whether oncolytic herpes simplex virus type 1 (HSV1 could eradicate chemoresistant cancer stem cells (CSCs. Methods The fluorescent aldefluor reagent-based technique was used to identify and isolate ALDHbr cells as CSCs from the 4T1 murine breast cancer cell line. The presence of ALDHbr 4T1 cells was also examined in 4T1 breast cancer transplanted in immune-competent syngeneic mice. Results Compared with ALDHlo cells, ALDHbr cells had a markedly higher ability to form tumor spheres in vitro and a higher tumorigenic potential in vivo. ALDHbr cells also exhibited increased doxorubicin resistance in vitro, which correlated with a selective increase in the percentage of ALDHbr cells after doxorubicin treatment and an increased expression of P-glycoprotein (P-gp, a known chemoresistance factor. In contrast, oncolytic HSV1 was able to kill ALDHbr cells in vitro and even more markedly in vivo. Furthermore, in in vivo studies, systemic administration of doxorubicin followed by intratumoral injection of oncolytic HSV1 resulted in much more significant suppression of tumor growth with increased median survival period compared with each treatment given alone (p+ T lymphocytes were induced by oncolytic HSV1, no significant specific T cell response against CSCs was detected in vivo. Conclusions These results suggested that the use of oncolytic HSV1 following doxorubicin treatment may help eradicate residual chemoresistant CSCs in vivo.

  1. The equine herpesvirus 1 gene 63 RING finger protein partially complements Vmw110, its herpes simplex virus type 1 counterpart.

    Science.gov (United States)

    Everett, R; Orr, A; Elliott, M

    1995-09-01

    All alpha herpesviruses of known DNA sequence have been found to encode a protein with similarities to immediate early protein Vmw110 (ICP0) of herpes simplex virus type 1 (HSV-1). The conserved portion of this family of proteins is a characteristic zinc binding module, known as a RING finger or C3HC4 domain. Examples of RING finger domains occur in many other proteins of diverse evolutionary origin and function. Recently, the solution structure of the equine herpesvirus 1 (EHV-1) RING finger protein, encoded by gene 63, has been solved. To investigate whether this structure could be considered to be a paradigm of herpesvirus RING domains, we have constructed a recombinant HSV-1 which expresses the EHV-1 gene 63 protein (EHVg63) in place of Vmw110. Comparison of the growth properties of the recombinant with those of wild-type and Vmw110-defective viruses indicates that EHVg63 is able to fulfil partially, but not completely, the roles of Vmw110 during virus growth in tissue culture.

  2. Neonatal Herpes Simplex Virus Type 1 Infection and Jewish Ritual Circumcision With Oral Suction: A Systematic Review.

    Science.gov (United States)

    Leas, Brian F; Umscheid, Craig A

    2015-06-01

    Jewish ritual circumcision rarely but occasionally includes a procedure involving direct oral suction of the wound, which can expose an infant to infection with herpes simplex virus type 1 (HSV-1). This practice has provoked international controversy in recent years, but no systematic review of the clinical literature has previously been published. We designed this review to identify and synthesize all published studies examining the association between circumcision with direct oral suction and HSV-1 infection. Our search strategy identified 6 published case series or case reports, documenting 30 cases between 1988 and 2012. Clinical findings were consistent with transmission of infection during circumcision, although the evidence base is limited by the small number of infections and incomplete case data. Published evidence suggests that circumcision with direct oral suction has resulted in severe neonatal illness and death from HSV-1 transmission, but further research is necessary to clarify the risk of infection. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Neonatal testicular cell transplantation restores murine spermatogenesis damaged in the course of herpes simplex virus-induced orchitis.

    Science.gov (United States)

    Malolina, Ekaterina A; Kulibin, Andrey Yu; Kushch, Alla A

    2016-04-01

    Genital tract infection and inflammation may affect male fertility, causing germ and Sertoli cell loss. We determined if testicular cell transplantation is effective at repairing testicular injury induced by herpes simplex virus (HSV) orchitis. ROSA26 mice were used as donors and the recipients were C57BL/6 mice after HSV testicular inoculation; some of the recipients were treated with the antiviral drug acyclovir (ACV). ACV reduced the amount of HSV antigen in testes on Day 3 after transplantation and enhanced the efficacy of transplantation at Day 30. In recipient testes, donor Sertoli cells formed new seminiferous tubules; significantly more new tubules were observed in the testes of ACV-treated mice compared with mice not treated with ACV (17.8% vs 3.6%). Over half (50.4%) of new tubules in ACV-treated testes contained germ cells and round spermatids were detected in 14.2% of new tubules compared with 15.9% and 5.3% in testes not treated with ACV, respectively. At Day 150 the seminiferous epithelium was completely recovered in some donor tubules and elongated spermatids were observed inside it. Thus, our findings reveal the effectiveness of the combination of antiviral therapy with neonatal testis-cell transplantation for the restoration of spermatogenesis damaged by viral infection.

  4. Resistance of herpes simplex viruses to acyclovir: an update from a ten-year survey in France.

    Science.gov (United States)

    Frobert, Emilie; Burrel, Sonia; Ducastelle-Lepretre, Sophie; Billaud, Geneviève; Ader, Florence; Casalegno, Jean-Sébastien; Nave, Viviane; Boutolleau, David; Michallet, Mauricette; Lina, Bruno; Morfin, Florence

    2014-11-01

    The widespread use of acyclovir (ACV) and the increasing number of immunocompromised patients have raised concern about an increase in ACV-resistant herpes simplex virus (HSV). ACV resistance has traditionally been a major concern for immunocompromised patients with a frequency reported between 2.5% and 10%. The aim of this study was to reassess the status of HSV resistance to ACV in immunocompetent and immunocompromised patients over a ten year period, between 2002 and 2011. This was done by retrospectively following 1425 patients. In immunocompetent patients, prevalence of resistance did not exceed 0.5% during the study period; whereas in immunocompromised patients, a significant increase was observed, rising from 3.8% between 2002 and 2006 (7/182 patients) to 15.7% between 2007 and 2011 (28/178) (p=0.0001). This sharp rise in resistance may largely be represented by allogeneic hematopoietic stem cell transplant patients, in which the prevalence of ACV resistance rose similarly from 14.3% (4/28) between 2002 and 2006 to 46.5% (26/56) between 2007 and 2011 (p=0.005). No increase in ACV resistance was detected in association with other types of immune deficiencies. Genotypic characterization of HSV UL23 thymidine kinase and UL30 DNA polymerase genes revealed 11 and 7 previously unreported substitutions, respectively. These substitutions may be related to potential polymorphisms, drug resistance, or other mutations of unclear significance.

  5. Monitoring of bystander effect of herpes simplex virus thymidine kinase/acyclovir system using fluorescence resonance energy transfer technique.

    Science.gov (United States)

    Xiong, Tao; Li, Yongjun; Ni, Fenge; Zhang, Feng

    2012-02-01

    Cytotoxic gene therapy mediated by gene transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene followed by acyclovir (ACV) treatment has been reported to inhibit malignant tumor growth in a variety of studies. The magnitude of "bystander effect" is an essential factor for this anti-tumor approach in vivo. However, the mechanism by which HSV-tk/ACV brings "bystander effect" is poorly understood. In this report, the plasmid CD3 (ECFP-CRS-DsRed) and TK-GFP were transferred to the human adenoid cystic carcinoma line ACC-M cell line. The CD3-expressing cells apoptosis was monitored using fluorescence resonance energy transfer (FRET) technique. First, CD3 and TK-GFP co-expressing ACC-M cells apoptosis was monitored using FRET technique. The apoptosis was induced by ACV and initiated by caspase3. The FRET efficient was remarkably decreased and then disappeared during cellular apoptosis, which indicated that the TK-GFP expressing ACC-M cells apoptosis, induced by ACV, was via a caspase3-dependent pathway. Secondly, CD3 and TK-GFP mixed expressing ACC-M cells apoptosis, induced by ACV, were monitored using FRET technique. The apoptotic phenomena appeared in the CD3-expressing ACC-M cells. The results show that HSV-tk/ACV system killed ACC-M cells using its bystander effect. These results confirm that HSV-tk/ACV system is potential for cancer gene therapy.

  6. Comparative study of inactivation of herpes simplex virus types 1 and 2 by commonly used antiseptic agents

    Energy Technology Data Exchange (ETDEWEB)

    Croughan, W.S.; Behbehani, A.M.

    1988-02-01

    A comparative study of the different reactions of herpes simplex virus types 1 and 2 to Lysol, Listerine, bleach, rubbing alcohol, Alcide disinfectant (Alcide Corp., Westport, Conn.), and various pHs, temperatures, and UV light exposures was performed. Both types of stock virus (titers of approximately 10(6) and 10(5.5) for types 1 and 2, respectively) were inactivated by 0.5% Lysol in 5 min; by Listerine (1:1 mixtures) in 5 min; by 2000 ppm (2000 microliters/liter) of bleach in 10 min; by rubbing alcohol (1:1 mixtures) at zero time; by Alcide disinfectant (0.2 ml of virus plus 2.0 ml of Alcide) at zero time; by pHs 3, 5, and 11 in 10 min; and by a temperature of 56 degrees C in 30 min. A germicidal lamp at a distance of 48 cm failed to completely inactivate the two types in 15 min. Type 1 showed slightly more resistance to Listerine and bleach and significantly more resistance to heat; moreover, pH 9 did not affect the infectivity of either type after 10 min.

  7. Comparative study of inactivation of herpes simplex virus types 1 and 2 by commonly used antiseptic agents.

    Science.gov (United States)

    Croughan, W S; Behbehani, A M

    1988-02-01

    A comparative study of the different reactions of herpes simplex virus types 1 and 2 to Lysol, Listerine, bleach, rubbing alcohol, Alcide disinfectant (Alcide Corp., Westport, Conn.), and various pHs, temperatures, and UV light exposures was performed. Both types of stock virus (titers of approximately 10(6) and 10(5.5) for types 1 and 2, respectively) were inactivated by 0.5% Lysol in 5 min; by Listerine (1:1 mixtures) in 5 min; by 2,000 ppm (2,000 microliters/liter) of bleach in 10 min; by rubbing alcohol (1:1 mixtures) at zero time; by Alcide disinfectant (0.2 ml of virus plus 2.0 ml of Alcide) at zero time; by pHs 3, 5, and 11 in 10 min; and by a temperature of 56 degrees C in 30 min. A germicidal lamp (model G30TB; General Electric Co., Schenectady, N.Y.) (30 W) at a distance of 48 cm failed to completely inactivate the two types in 15 min. Type 1 showed slightly more resistance to Listerine and bleach and significantly more resistance to heat; moreover, pH 9 did not affect the infectivity of either type after 10 min.

  8. Therapeutic efficacy of G207, a conditionally replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters.

    Science.gov (United States)

    Nakano, K; Todo, T; Chijiiwa, K; Tanaka, M

    2001-04-01

    Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and one hamster) showed nearly total cell killing within 72 h of G207 infection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 x 10(7) pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regression or growth reduction of uninoculated tumors as well as inoculated tumors. In athymic mice, however, the anti-tumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemic anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.

  9. Herpes Simplex Virus Type-I and Pyogenic Granuloma: A Vascular Endothelial Growth Factor-Mediated Association

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    L. el Hayderi

    2013-08-01

    Full Text Available Pyogenic granuloma (PG is a vascular endothelial growth factor (VEGF-related neoangiogenic process. Minor trauma, chronic irritation, certain drugs and pregnancy may favor PG. Viral triggers have not been reported up to date. A 52-year-old woman with hairy-cell leukemia presented because of a 3-month history of a giant pseudotumoral lesion on her left cheek. All prior antibacterial, antifungal and anti-inflammatory treatments had failed. Histology revealed PG with sparse and isolated epithelial cell aggregates. Immunohistochemistry (IHC identified herpes simplex virus type-I (HSV-I antigens in the nuclei and cytoplasm of normal-appearing as well as cytopathic epithelial cells, suggesting a chronic, low-productive HSV infection. No HSV-I signal was evidenced in the endothelial cells of the PG. Furthermore, IHC revealed VEGF in the HSV-I infected epithelial cells as well as within the PG endothelial cells. These results incited oral treatment with valaciclovir, and the PG promptly resolved after 2 weeks. These findings suggest that a chronic HSV-I infection might play an indirect, partial role in neoangiogenesis, presumably via HSV-I infection-related stimulation of keratinocytic VEGF production.

  10. Visualization of mouse neuronal ganglia infected by Herpes Simplex Virus 1 (HSV-1 using multimodal non-linear optical microscopy.

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    Pierre-Alexandre Rochette

    Full Text Available Herpes simplex virus 1 (HSV-1 is a neurotropic virus that causes skin lesions and goes on to enter a latent state in neurons of the trigeminal ganglia. Following stress, the virus may reactivate from latency leading to recurrent lesions. The in situ study of neuronal infections by HSV-1 is critical to understanding the mechanisms involved in the biology of this virus and how it causes disease; however, this normally requires fixation and sectioning of the target tissues followed by treatment with contrast agents to visualize key structures, which can lead to artifacts. To further our ability to study HSV-1 neuropathogenesis, we have generated a recombinant virus expressing a second generation red fluorescent protein (mCherry, which behaves like the parental virus in vivo. By optimizing the application of a multimodal non-linear optical microscopy platform, we have successfully visualized in unsectioned trigeminal ganglia of mice both infected cells by two-photon fluorescence microscopy, and myelinated axons of uninfected surrounding cells by coherent anti-Stokes Raman scattering (CARS microscopy. These results represent the first report of CARS microscopy being combined with 2-photon fluorescence microscopy to visualize virus-infected cells deep within unsectioned explanted tissue, and demonstrate the application of multimodal non-linear optical microscopy for high spatial resolution biological imaging of tissues without the use of stains or fixatives.

  11. Herpes simplex virus 1 VP22 regulates translocation of multiple viral and cellular proteins and promotes neurovirulence.

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    Tanaka, Michiko; Kato, Akihisa; Satoh, Yuko; Ide, Takahiro; Sagou, Ken; Kimura, Kayo; Hasegawa, Hideki; Kawaguchi, Yasushi

    2012-05-01

    Herpes simplex virus 1 (HSV-1) protein VP22, encoded by the UL49 gene, is a major virion tegument protein. In the present study, we showed that VP22 was required for efficient redistribution of viral proteins VP16, VP26, ICP0, ICP4, and ICP27 and of cellular protein Hsc-70 to the cytoplasm of infected cells. We found that two dileucine motifs in VP22, at amino acids 235 and 236 and amino acids 251 and 252, were necessary for VP22 regulation of the proper cytoplasmic localization of these viral and cellular proteins. The dileucine motifs were also required for proper cytoplasmic localization of VP22 itself and for optimal expression of viral proteins VP16, VP22, ICP0, UL41, and glycoprotein B. Interestingly, a recombinant mutant virus with alanines substituted for the dileucines at amino acids 251 and 252 had a 50% lethal dose (LD(50)) for neurovirulence in mice following intracerebral inoculation about 10(3)-fold lower than the LD(50) of the repaired virus. Furthermore, the replication and spread of this mutant virus in the brains of mice following intracerebral inoculation were significantly impaired relative to those of the repaired virus. The ability of VP22 to regulate the localization and expression of various viral and cellular proteins, as shown in this study, was correlated with an increase in viral replication and neurovirulence in the experimental murine model. Thus, HSV-1 VP22 is a significant neurovirulence factor in vivo.

  12. Herpes Simplex Virus Type-1 (HSV-1 Entry into Human Mesenchymal Stem Cells Is Heavily Dependent on Heparan Sulfate

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    Samiksha Choudhary

    2011-01-01

    Full Text Available Hematopoietic stem cells recipients remain susceptible to opportunistic viral infections including herpes simplex virus type-1 (HSV-1. The purpose of this investigation was to analyze susceptibility of human mesenchymal stem cells (hMSCs to HSV-1 infection and identify the major entry receptor. Productive virus infection in hMSCs was confirmed by replication and plaque formation assays using a syncytial HSV-1 KOS (804 virus. To examine the significance of entry receptors, RT-PCR and antibody-blocking assays were performed. RT-PCR data showed the expression of gD receptors: nectin-1, 3-O sulfotransferase-3 (3-OST-3, and HVEM. Antibody-blocking assay together with heparinase treatment suggested an important role for HS and 3-O-sulfated heparan sulfate (3-OS HS, but not nectin-1 or HVEM, in mediating HSV-1 entry and spread in hMSCs. Taken together, our results provide strong evidence demonstrating that HSV-1 is capable of infecting hMSCs and HS and 3-OS HS serve as its entry receptors during this process.

  13. Blocking of PDL-1 interaction enhances primary and secondary CD8 T cell response to herpes simplex virus-1 infection.

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    Rudragouda Channappanavar

    Full Text Available The blocking of programmed death ligand-1 (PDL-1 has been shown to enhance virus-specific CD8 T cell function during chronic viral infections. Though, how PDL-1 blocking at the time of priming affects the quality of CD8 T cell response to acute infections is not well understood and remains controversial. This report demonstrates that the magnitude of the primary and secondary CD8 T cell responses to herpes simplex virus-1 (HSV-1 infection is subject to control by PDL-1. Our results showed that after footpad HSV-1 infection, PD-1 expression increases on immunodominant SSIEFARL peptide specific CD8 T cells. Additionally, post-infection, the level of PDL-1 expression also increases on CD11c+ dendritic cells. Intraperitoneal administration of anti-PDL-1 monoclonal antibody given one day prior to and three days after cutaneous HSV-1 infection, resulted in a marked increase in effector and memory CD8 T cell response to SSIEFARL peptide. This was shown by measuring the quantity and quality of SSIEFARL-specific CD8 T cells by making use of ex-vivo assays that determine antigen specific CD8 T cell function, such as intracellular cytokine assay, degranulation assay to measure cytotoxicity and viral clearance. Our results are discussed in terms of the beneficial effects of blocking PDL-1 interactions, while giving prophylactic vaccines, to generate a more effective CD8 T cell response to viral infection.

  14. Performance of the HSV OligoGen kit for the diagnosis of herpes simplex virus type 1 and 2.

    Science.gov (United States)

    Parra-Sánchez, Manuel; Marcuello López, Ana; García-Rey, Silvia; Zakariya-Yousef Breval, Ismail; Bernal Martínez, Samuel; Pueyo Rodríguez, Isabel; Martín-Mazuelos, Estrella; Palomares Folía, José Carlos

    2016-07-01

    PCR methods are nowadays between the most rapid and sensitive methods for screening and diagnosing herpes simplex virus (HSV) type 1 and 2. The aim of this study was to analyze the reliability, accuracy, and usefulness of the new assay HSV OligoGen kit in comparison with the Roche LightCycler HSV ½ Qual Kit assay for the detection of HSV in clinical samples. For this analysis, a prospective study was designed for detection of HSV-1 and HSV-2 including 110 ulcer specimens, 48 urine, 48 endocervical, 43 cerebral spinal fluids, 4 urethral and 3 pharyngeal swabs that were sent from a regional STI clinic or an Intensive Clinical Unit, both in Seville, Spain. In comparison to the Roche LightCycler HSV ½ Qual Kit assay, sensitivity, specificity, positive and negative predicative values, and kappa value for HSV detection using the HSV OligoGen kit were 96.2%, 100%, 100%, 98.3%, and 0.97 for HSV-1, respectively. For HSV-2, the corresponding values were 98.3%, 100%, 100%, 99.5%, and 0.98, respectively. Statistical data obtained in this study confirms the usefulness and reliable results of this new assay.

  15. Application of polymerase chain reaction to differentiate herpes simplex virus 1 and 2 serotypes in culture negative intraocular aspirates

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    Shyamal G

    2005-01-01

    Full Text Available Purpose: To standardize and apply a polymerase chain reaction (PCR on the glycoprotein D gene to differentiate Herpes simplex virus (HSV 1 & 2 serotypes in culture negative intraocular specimens. Methods: Twenty-one intraocular fluids collected from 19 patients were subjected to cultures for HSV and uniplex PCR (uPCR for DNA polymerase gene. To differentiate HSV serotypes, as 1 & 2, a seminested PCR (snPCR targeting the glycoprotein D gene was standardised and applied onto 21 intraocular fluids. The specificity of the snPCR was verified by application onto ATCC strains of HSV 1 and 2, clinical isolates and DNA sequencing of the amplified products. All specimens were also tested for the presence of cytomegalovirus (CMV and varicella zoster virus (VZV by nucleic acid amplification methods. Results: Four of the 21 intraocular fluids were positive for HSV by uPCR. snPCR detected HSV in three additional specimens (total of seven specimens, and identified three as HSV 1 and four as HSV 2. DNA sequencing of PCR products showed 100% homology with the standard strains of HSV 1 and 2 respectively. None of the samples were positive in culture. Among the other patients, CMV DNA was detected in two and VZV DNA in five others. Conclusions: The standardized snPCR can be applied directly onto the culture negative specimens for rapid differentiation of HSV serotypes.

  16. Acute Interstitial Nephritis Proteinuria and Herpes Simplex Virus Hepatitis in Pregnancy Mimic HELLP Syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelets

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    Wendy M. White

    2011-12-01

    Full Text Available Elevated transaminases, hemolysis, and thrombocytopenia in pregnancy are most often caused by a preeclampsia variant—HELLP syndrome (hemolysis, elevated liver enzymes, low platelets. In atypical cases, it is important to consider other causes, such as herpes simplex virus (HSV hepatitis. Acute interstitial nephritis (AIN-induced proteinuria can make distinguishing HELLP from its mimics more difficult. A 43-year-old G4P3 gestational carrier at 28 weeks had abnormal laboratory findings consistent with HELLP, including proteinuria. However, she was normotensive and febrile, prompting an investigation into other possible causes of her signs and symptoms. She ultimately was diagnosed with disseminated HSV infection, started on definitive therapy, and allowed to continue her pregnancy to term. The proteinuria was attributed to AIN. AIN can cause proteinuria in the critically ill pregnant patient. When mimics of HELLP syndrome, such as disseminated HSV infection, are the cause of critical illness, the presence of AIN-induced proteinuria may falsely implicate a hypertensive disorder of pregnancy, resulting in iatrogenic premature delivery of the fetus and failure to initiate definitive potential lifesaving treatment.

  17. Diagnosis of herpes simplex virus-1 keratitis using Giemsa stain, immunofluorescence assay, and polymerase chain reaction assay on corneal scrapings

    Science.gov (United States)

    Farhatullah, S; Kaza, S; Athmanathan, S; Garg, P; Reddy, S B; Sharma, S

    2004-01-01

    Aims: To evaluate three tests used routinely for the diagnosis of herpes simplex virus (HSV) keratitis. Methods: Corneal scrapings from 28 patients with clinically typical dendritic corneal ulcer suggestive of HSV keratitis, and 30 patients with clinically non-viral corneal ulcers, were tested by (i) Giemsa stain for multinucleated giant cells, (ii) immunofluorescence assay (IFA) for HSV-1 antigen, and (iii) polymerase chain reaction (PCR) for HSV-1 DNA, by investigators masked to clinical diagnosis. The control subjects were also investigated by smears and cultures for bacteria, fungus, and Acanthamoeba. Results: The specificity and positive predictive values of all three tests for the diagnosis of HSV keratitis were between 95–100%. The sensitivity of IFA and PCR was 78.6% and 81.2%, respectively, and the difference was not significant; however, their sensitivity and negative predictive value were significantly higher than Giemsa stain. Conclusions: While a combination of IFA and PCR constitute the choice of tests in clinically suspected cases of HSV keratitis, multinucleated giant cells in Giemsa stain can pre-empt testing by IFA and PCR in otherwise atypical cases of HSV keratitis. PMID:14693792

  18. The product of the Herpes simplex virus 1 UL7 gene interacts with a mitochondrial protein, adenine nucleotide translocator 2

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    Kawaguchi Yasushi

    2008-10-01

    Full Text Available Abstract The herpes simplex virus 1 (HSV-1 UL7 gene is highly conserved among herpesviridae. Since the construction of recombinant HSV-1 with a mutation in the UL7 gene has not been reported, the involvement of HSV-1 UL7 in viral replication has been unclear. In this study, we succeeded in generating a UL7 null HSV-1 mutant virus, MT102, and characterized it. Our results were as follows. (i In Vero cells, MT102 was replication-competent, but formed smaller plaques and yielded 10- to 100-fold fewer progeny than the wild-type virus, depending on the multiplicity of infection. (ii Using mass spectrometry-based proteomics technology, we identified a cellular mitochondrial protein, adenine nucleotide translocator 2 (ANT2, as a UL7-interacting partner. (iii When ANT2 was transiently expressed in COS-7 cells infected with HSV-1, ANT2 was specifically co-precipitated with UL7. (iv Cell fractionation experiments with HSV-1-infected cells detected the UL7 protein in both the mitochondrial and cytosolic fractions, whereas ANT2 was detected only in the mitochondrial fraction. These results indicate the importance of HSV-1 UL7's involvement in viral replication and demonstrate that it interacts with ANT2 in infected cells. The potential biological significance of the interaction between UL7 and ANT2 is discussed.

  19. Medroxyprogesterone acetate and levonorgestrel increase genital mucosal permeability and enhance susceptibility to genital herpes simplex virus type 2 infection.

    Science.gov (United States)

    Quispe Calla, N E; Vicetti Miguel, R D; Boyaka, P N; Hall-Stoodley, L; Kaur, B; Trout, W; Pavelko, S D; Cherpes, T L

    2016-11-01

    Depot-medroxyprogesterone acetate (DMPA) is a hormonal contraceptive especially popular in areas with high prevalence of HIV and other sexually transmitted infections (STI). Although observational studies identify DMPA as an important STI risk factor, mechanisms underlying this connection are undefined. Levonorgestrel (LNG) is another progestin used for hormonal contraception, but its effect on STI susceptibility is much less explored. Using a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, we herein found that DMPA and LNG similarly reduced genital expression of the desmosomal cadherin desmoglein-1α (DSG1α), enhanced access of inflammatory cells to genital tissue by increasing mucosal epithelial permeability, and increased susceptibility to viral infection. Additional studies with uninfected mice revealed that DMPA-mediated increases in mucosal permeability promoted tissue inflammation by facilitating endogenous vaginal microbiota invasion. Conversely, concomitant treatment of mice with DMPA and intravaginal estrogen restored mucosal barrier function and prevented HSV-2 infection. Evaluating ectocervical biopsy tissue from women before and 1 month after initiating DMPA remarkably revealed that inflammation and barrier protection were altered by treatment identically to changes seen in progestin-treated mice. Together, our work reveals DMPA and LNG diminish the genital mucosal barrier; a first-line defense against all STI, but may offer foundation for new contraceptive strategies less compromising of barrier protection.

  20. Antigen-specific immune-suppressor factor in herpes simplex virus type 2 infections of UV B-irradiated mice

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    Aurelian, L.; Yasumoto, S.; Smith, C.C.

    1988-07-01

    UV B-irradiation (280 to 320 nm) of mice at the site of cutaneous infection with herpes simplex virus type 2 (HSV-2) induced suppressor T-cell circuits that decreased HSV-2-induced proliferative responses of HSV-2-immune lymph node cells. Adoptive transfer experiments indicated that splenocytes from UV B-irradiated HSV-2-infected animals contain L3T4+ cells that suppress proliferative responses in vivo, consistent with suppressor inducer cells. However, following in vitro culture of the splenocytes with HSV-2 antigen, the proliferation of immune lymph node cells was inhibited by Lyt2+ suppressor T cells, consistent with antigen-induced suppressor effector cells. Antigen-specific and nonspecific suppressor factors were fractionated from supernatants of HSV-2-stimulated spleen cells by molecular-sieve chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the Sephadex fraction that contained the antigen-specific suppressor factor, in the presence or absence of 2-mercaptoethanol, defined a 115-kilodalton protein consisting of two disulfide-bound components with molecular sizes of 70 and 52 kilodaltons. The implications of these results with respect to the regulation of HSV-induced cell-mediated immunity following UV B-irradiation are discussed.