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Sample records for herpes virus tipo

  1. Herpes zoster virus vaccine.

    PubMed

    Woolery, William Alan

    2008-10-01

    Varicella zoster virus (VZV) is the etiologic agent of varicella and herpes zoster (HZ) in humans. Herpes zoster is the result of reactivation of VZV within certain sensory ganglia. The burden of illness from HZ and post-herpetic neuralgia (PHN) is high. Herpes-zoster vaccine contains live attenuated varicella-zoster virus in an amount approximately 14 times greater than that found in the varicella virus vaccine. Herpes zoster vaccine is approved for the prevention of shingles in appropriate persons aged 60 and older. The vaccine is administered in a single subcutaneous dose. Reported side effects are mild and generally limited to localized injection site findings. Herpes-zoster vaccine reportedly decreases the occurrence of herpes zoster by approximately 50 percent and prevents the development of PHN by two thirds. The vaccine appears to be minimally effective in those individuals over the age of 80 and is not recommended in this age group.

  2. Herpes Virus Amplicon Vectors

    PubMed Central

    de Silva, Suresh; Bowers, William J.

    2009-01-01

    Since its emergence onto the gene therapy scene nearly 25 years ago, the replication-defective Herpes Simplex Virus Type-1 (HSV-1) amplicon has gained significance as a versatile gene transfer platform due to its extensive transgene capacity, widespread cellular tropism, minimal immunogenicity, and its amenability to genetic manipulation. Herein, we detail the recent advances made with respect to the design of the HSV amplicon, its numerous in vitro and in vivo applications, and the current impediments this virus-based gene transfer platform faces as it navigates a challenging path towards future clinical testing. PMID:19956558

  3. Neonatal herpes simplex virus infections.

    PubMed

    Pinninti, Swetha G; Kimberlin, David W

    2013-04-01

    Neonatal herpes simplex virus infections are uncommon, but because of the morbidity and mortality associated with the infection they are often considered in the differential diagnosis of ill neonates. The use of polymerase chain reaction for diagnosis of central nervous system infections and the development of safe and effective antiviral therapy has revolutionized the diagnosis and management of these infants. Initiation of long-term antiviral suppressive therapy in these infants has led to significant improvement in morbidity. This article summarizes the epidemiology of neonatal herpes simplex virus infections and discusses clinical presentation, diagnosis, management, and follow up of infants with neonatal herpes disease.

  4. Neonatal herpes simplex virus infection.

    PubMed

    Cherpes, Thomas L; Matthews, Dean B; Maryak, Samantha A

    2012-12-01

    Neonatal herpes, seen roughly in 1 of 3000 live births in the United States, is the most serious manifestation of herpes simplex virus (HSV) infection in the perinatal period. Although acyclovir therapy decreases infant mortality associated with perinatal HSV transmission, development of permanent neurological disabilities is not uncommon. Mother-to-neonate HSV transmission is most efficient when maternal genital tract HSV infection is acquired proximate to the time of delivery, signifying that neonatal herpes prevention strategies need to focus on decreasing the incidence of maternal infection during pregnancy and more precisely identifying infants most likely to benefit from prophylactic antiviral therapy.

  5. Herpes simplex virus following stab phlebectomy.

    PubMed

    Hicks, Caitlin W; Lum, Ying Wei; Heller, Jennifer A

    2017-03-01

    Herpes simplex virus infection following surgery is an unusual postoperative phenomenon. Many mechanisms have been suggested, with the most likely explanation related to latent virus reactivation due to a proinflammatory response in the setting of local trauma. Here, we present a case of herpes simplex virus reactivation in an immunocompetent female following a conventional right lower extremity stab phlebectomy. Salient clinical and physical examination findings are described, and management strategies for herpes simplex virus reactivation are outlined. This is the first known case report of herpes simplex virus reactivation following lower extremity phlebectomy.

  6. Maternal and neonatal herpes simplex virus infections.

    PubMed

    Pinninti, Swetha G; Kimberlin, David W

    2013-02-01

    Genital herpes infections are extremely common worldwide and ~22% of pregnant women are infected with herpes simplex virus. Eighty percent of those affected with genital herpes are unaware of being infected. The most devastating consequence of maternal genital herpes is neonatal herpes disease. Fortunately, neonatal herpes simplex infections are uncommon but due to the morbidity and mortality associated with the infection are often considered in the differential diagnosis of ill neonates. The use of polymerase chain reaction assay for diagnosis of central nervous system infections and the development of safe and effective antiviral therapy have revolutionized the diagnosis and management of these infants. Most recently, the initiation of long-term antiviral suppressive therapy in these infants has led to significant improvement in morbidity. This review will summarize the epidemiology of maternal and neonatal herpes infections and discuss clinical presentation, diagnosis, management, and follow-up of infants with neonatal herpes disease.

  7. Neonatal Herpes Simplex Virus Infection.

    PubMed

    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.

  8. Herpes simplex virus infection during pregnancy.

    PubMed

    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.

  9. Designing herpes viruses as oncolytics

    PubMed Central

    Peters, Cole; Rabkin, Samuel D

    2015-01-01

    Oncolytic herpes simplex virus (oHSV) was one of the first genetically-engineered oncolytic viruses. Because HSV is a natural human pathogen that can cause serious disease, it is incumbent that it can be genetically-engineered or significantly attenuated for safety. Here, we present a detailed explanation of the functions of HSV-1 genes frequently mutated to endow oncolytic activity. These genes are nonessential for growth in tissue culture cells but are important for growth in postmitotic cells, interfering with intrinsic antiviral and innate immune responses or causing pathology, functions dispensable for replication in cancer cells. Understanding the function of these genes leads to informed creation of new oHSVs with better therapeutic efficacy. Virus infection and replication can also be directed to cancer cells through tumor-selective receptor binding and transcriptional- or post-transcriptional miRNA-targeting, respectively. In addition to the direct effects of oHSV on infected cancer cells and tumors, oHSV can be “armed” with transgenes that are: reporters, to track virus replication and spread; cytotoxic, to kill uninfected tumor cells; immune modulatory, to stimulate antitumor immunity; or tumor microenvironment altering, to enhance virus spread or to inhibit tumor growth. In addition to HSV-1, other alphaherpesviruses are also discussed for their oncolytic activity. PMID:26462293

  10. Pediatrics and herpes simplex virus vaccines.

    PubMed

    Rupp, Richard; Rosenthal, Susan L; Stanberry, Lawrence R

    2005-01-01

    This review explores the development of prophylactic genital herpes vaccines and their potential impact on perinatal and oral-facial disease. Vaccine strategies have included the use of whole killed virus, viral subunits, attenuated live virus, viral vectors, and bare DNA. To date, the recombinant subunit vaccine, truncated HSV-2 gD and alum/MPL, has been the most efficacious. The vaccine is 73 to 74 percent effective in preventing genital disease in herpes simplex virus seronegative women but is not effective in men or seropositive women. Models predict a significant impact on genital herpes if it limits viral shedding. Reductions in perinatal and oral-facial disease are likely to occur as well. Once an efficacious herpes vaccine is available, its effectiveness will depend ultimately on vaccine acceptance by professional organizations, healthcare professionals, and parents. Further research is required to improve on and fully understand the implications of prophylactic herpes simplex vaccines.

  11. Herpes simplex type-1 virus infection.

    PubMed

    Huber, Michaell A

    2003-06-01

    Oral infection caused by the herpes simplex virus represents one of the more common conditions the dental practitioner will be called upon to manage. Unique in its ability to establish latency and undergo subsequent recurrence, it is an ubiquitous infectious agent for which a cure does not exist. For the immunocompetent patient, herpes virus simplex infection typically represents nothing more than a nuisance. However, for the immunocompromised patient, this infection is associated with increased morbidity and mortality. Recently introduced antiviral drug regimens may reduce the morbidity and potential mortality of the herpes simplex virus, especially in immunocompromised patients. The value of antiviral therapy in the management of recurrent herpes simplex virus infection in the immunocompetent patient remains an area of contentious debate.

  12. Herpes Simplex Virus: Partner for Life

    PubMed Central

    Blondeau, Joseph M.; Embil, Juan A.

    1988-01-01

    The authors provide a careful review of the characteristics of the herpes simplex virus and its various manifestations. They offer suggestions for its diagnosis and treatment, in various forms, and outline an approach to physician counselling of infected persons.

  13. The management of herpes simplex virus infections.

    PubMed

    Yeung-Yue, Kimberly A; Brentjens, Mathijs H; Lee, Patricia C; Tyring, Stephen K

    2002-04-01

    Herpes simplex virus persists in a latent form for the life of its host, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently no cure is available. Antiviral therapy is the main treatment modality, used either orally, intravenously, or topically to prohibit further replication of the virus and thereby minimize cellular destruction. However, immunologic advances in the treatment and prevention of herpes simplex infections are promising and continue to be studied.

  14. [Immune evasion by herpes simplex viruses].

    PubMed

    Retamal-Díaz, Angello R; Suazo, Paula A; Garrido, Ignacio; Kalergis, Alexis M; González, Pablo A

    2015-02-01

    Herpes simplex viruses and humans have co-existed for tens of thousands of years. This long relationship has translated into the evolution and selection of viral determinants to evade the host immune response and reciprocally the evolution and selection of host immune components for limiting virus infection and damage. Currently there are no vaccines available to avoid infection with these viruses or therapies to cure them. Herpes simplex viruses are neurotropic and reside latently in neurons at the trigeminal and dorsal root ganglia, occasionally reactivating. Most viral recurrences are subclinical and thus, unnoticed. Here, we discuss the initial steps of infection by herpes simplex viruses and the molecular mechanisms they have developed to evade innate and adaptive immunity. A better understanding of the molecular mechanisms evolved by these viruses to evade host immunity should help us envision novel vaccine strategies and therapies that limit infection and dissemination.

  15. Herpes simplex virus Membrane Fusion.

    PubMed

    Weed, Darin J; Nicola, Anthony V

    2017-01-01

    Herpes simplex virus mediates multiple distinct fusion events during infection. HSV entry is initiated by fusion of the viral envelope with either the limiting membrane of a host cell endocytic compartment or the plasma membrane. In the infected cell during viral assembly, immature, enveloped HSV particles in the perinuclear space fuse with the outer nuclear membrane in a process termed de-envelopment. A cell infected with some strains of HSV with defined mutations spread to neighboring cells by a fusion event called syncytium formation. Two experimental methods, the transient cell-cell fusion approach and fusion from without, are useful surrogate assays of HSV fusion. These five fusion processes are considered in terms of their requirements, mechanism, and regulation. The execution and modulation of these events require distinct yet often overlapping sets of viral proteins and host cell factors. The core machinery of HSV gB, gD, and the heterodimer gH/gL is required for most if not all of the HSV fusion mechanisms.

  16. Can Herpes Simplex Virus Encephalitis Cause Aphasia?

    ERIC Educational Resources Information Center

    Naude, H.; Pretorius, E.

    2003-01-01

    Aphasia implies the loss or impairment of language caused by brain damage. The key to understanding the nature of aphasic symptoms is the neuro-anatomical site of brain damage, and not the causative agent. However, because "Herpes simplex" virus (HSV) encephalitis infection usually affects the frontal and temporal lobes, subcortical…

  17. Can Herpes Simplex Virus Encephalitis Cause Aphasia?

    ERIC Educational Resources Information Center

    Naude, H.; Pretorius, E.

    2003-01-01

    Aphasia implies the loss or impairment of language caused by brain damage. The key to understanding the nature of aphasic symptoms is the neuro-anatomical site of brain damage, and not the causative agent. However, because "Herpes simplex" virus (HSV) encephalitis infection usually affects the frontal and temporal lobes, subcortical…

  18. Preventing herpes simplex virus in the newborn.

    PubMed

    Pinninti, Swetha G; Kimberlin, David W

    2014-12-01

    Genital herpes simplex virus (HSV) infections are very common worldwide. Approximately 22% of pregnant women are infected genitally with HSV, and most of them are unaware of this. The most devastating consequence of maternal genital herpes is HSV disease in the newborn. Although neonatal HSV infections remain uncommon, due to the significant morbidity and mortality associated with the infection, HSV infection in the newborn is often considered in the differential diagnosis of ill neonates. This review summarizes the epidemiology and management of neonatal HSV infections and discusses strategies to prevent HSV infection in the newborn.

  19. Inactivation of Herpes Simplex Viruses by Nonionic Surfactants

    PubMed Central

    Asculai, Samuel S.; Weis, Margaret T.; Rancourt, Martha W.; Kupferberg, A. B.

    1978-01-01

    Nonionic surface-active agents possessing ether or amide linkages between the hydrophillic and hydrophobic portions of the molecule rapidly inactivated the infectivity of herpes simplex viruses. The activity stemmed from the ability of nonionic surfactants to dissolve lipid-containing membranes. This was confirmed by observing surfactant destruction of mammalian cell plasma membranes and herpes simplex virus envelopes. Proprietary vaginal contraceptive formulations containing nonionic surfactants also inactivated herpes simplex virus infectivity. This observation suggests that nonionic surfactants in appropriate formulation could effectively prevent herpes simplex virus transmission. Images PMID:208460

  20. Vaccinia Virus Recombinant Expressing Herpes Simplex Virus Type 1 Glycoprotein D Prevents Latent Herpes in Mice

    NASA Astrophysics Data System (ADS)

    Cremer, Kenneth J.; Mackett, Michael; Wohlenberg, Charles; Notkins, Abner Louis; Moss, Bernard

    1985-05-01

    In humans, herpes simplex virus causes a primary infection and then often a latent ganglionic infection that persists for life. Because these latent infections can recur periodically, vaccines are needed that can protect against both primary and latent herpes simplex infections. Infectious vaccinia virus recombinants that contain the herpes simplex virus type 1 (HSV-1) glycoprotein D gene under control of defined early or late vaccinia virus promoters were constructed. Tissue culture cells infected with these recombinant viruses synthesized a glycosylated protein that had the same mass (60,000 daltons) as the glycoprotein D produced by HSV-1. Immunization of mice with one of these recombinant viruses by intradermal, subcutaneous, or intraperitoneal routes resulted in the production of antibodies that neutralized HSV-1 and protected the mice against subsequent lethal challenge with HSV-1 or HSV-2. Immunization with the recombinant virus also protected the majority of the mice against the development of a latent HSV-1 infection of the trigeminal ganglia. This is the first demonstration that a genetically engineered vaccine can prevent the development of latency.

  1. Update on oral herpes virus infections.

    PubMed

    Balasubramaniam, Ramesh; Kuperstein, Arthur S; Stoopler, Eric T

    2014-04-01

    Oral herpes virus infections (OHVIs) are among the most common mucosal disorders encountered by oral health care providers. These infections can affect individuals at any age, from infants to the elderly, and may cause significant pain and dysfunction. Immunosuppressed patients may be at increased risk for serious and potential life-threatening complications caused by OHVIs. Clinicians may have difficulty in diagnosing these infections because they can mimic other conditions of the oral mucosa. This article provides oral health care providers with clinically relevant information regarding etiopathogenesis, diagnosis, and management of OHVIs.

  2. Herpes simplex virus and the alimentary tract.

    PubMed

    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.

  3. THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS

    PubMed Central

    Johnson, Richard T.

    1964-01-01

    The pathogenesis of herpes simplex virus encephalitis and myelitis was studied in suckling mice using routine titration procedures and fluorescent antibody staining for the identification of infected cells. After intracerebral inoculation virus was shown to disperse rapidly in the cerebrospinal fluid (CSF), multiply in meninges and ependyma, and then invade the underlying parenchyma infecting both neurons and glia. Following extraneural inoculation virus gained access to the central nervous system (CNS) by both hematogenous and neural pathways. After intraperitoneal and intranasal inoculation virus was found to multiply in viscera and produce viremia; foci of CNS infection then developed around small cerebral vessels. After subcutaneous and intranasal inoculation neural spread of virus was demonstrated along corresponding peripheral and cranial nerves. This spread resulted from the centripetal infection of endoneural cells (Schwann cells and fibroblasts). Antigen was not found in axons even after infection of the corresponding ganglion cell perikaryon. Subsequent spread within the CNS was unrelated to neural tracts, and there was no evidence of axonal spread of virus in the host-virus system studied. These findings are discussed in relation to previous and current theories of the viral "blood-brain barrier" and neural pathways of infection. PMID:14164487

  4. Characterizing human herpes virus 6 following hematopoietic stem cell transplantation.

    PubMed

    Perissinotti, Anthony J; Gulbis, Alison; Shpall, Elizabeth J; Howell, Joshua

    2015-04-01

    Human herpes virus 6 reactivation occurs in approximately 50% of patients following hematopoietic stem cell transplant, however, the significance of human herpes virus 6 reactivation remains uncertain. A retrospective study was conducted analyzing clinical data of patients testing positive for human herpes virus 6 by quantitative polymerase chain reaction following hematopoietic stem cell transplant from 1 January 1998 to 1 October 2011. Data retrieved were used to describe the clinical course and outcome of human herpes virus 6 positive hematopoietic stem cell transplant patients. Sixty patients were identified who tested positive for human herpes virus 6 by polymerase chain reaction following hematopoietic stem cell transplant. A high proportion of patients were identified in this cohort with acute myeloid leukemia (28.3%), active disease (65%), transplanted with a matched unrelated donor (30%), ≥ 1 antigen mismatched (28.3%) matched unrelated donor, or an umbilical cord graft (25%), and those who received antithymocyte globulin (42.4%). Thirty-eight (63.3%) patients were treated for human herpes virus 6 with foscarnet alone or in combination with intravenous immunoglobulin, whereas 18 (30%) did not require treatment survival at Day 100 was 73.3%. This study suggests human herpes virus 6 reactivation occurs shortly after hematopoietic stem cell transplant (median of 25 days (interquartile range, 20-31.75) after hematopoietic stem cell transplant). Many potential risk factors are described in this report. Treatment of human herpes virus 6 predominately consisted of foscarnet with or without intravenous immunoglobulin; however, treatment of human herpes virus 6 was not always warranted. Furthermore, the effect of treatment on patient outcomes is uncertain. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  5. 76 FR 48715 - Immunology and Microbiology Devices; Reclassification of the Herpes Simplex Virus Serological...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-09

    ...; Reclassification of the Herpes Simplex Virus Serological Assay Device AGENCY: Food and Drug Administration, HHS... the herpes simplex virus (HSV) serological assay device type, which is classified as class II (special... tests to identify antibodies to herpes simplex virus in serum, and the devices that consist of herpes...

  6. Experimental investigation of herpes simplex virus latency.

    PubMed Central

    Wagner, E K; Bloom, D C

    1997-01-01

    The clinical manifestations of herpes simplex virus infection generally involve a mild and localized primary infection followed by asymptomatic (latent) infection interrupted sporadically by periods of recrudescence (reactivation) where virus replication and associated cytopathologic findings are manifest at the site of initial infection. During the latent phase of infection, viral genomes, but not infectious virus itself, can be detected in sensory and autonomic neurons. The process of latent infection and reactivation has been subject to continuing investigation in animal models and, more recently, in cultured cells. The initiation and maintenance of latent infection in neurons are apparently passive phenomena in that no virus gene products need be expressed or are required. Despite this, a single latency-associated transcript (LAT) encoded by DNA encompassing about 6% of the viral genome is expressed during latent infection in a minority of neurons containing viral DNA. This transcript is spliced, and the intron derived from this splicing is stably maintained in the nucleus of neurons expressing it. Reactivation, which can be induced by stress and assayed in several animal models, is facilitated by the expression of LAT. Although the mechanism of action of LAT-mediated facilitation of reactivation is not clear, all available evidence argues against its involving the expression of a protein. Rather, the most consistent models of action involve LAT expression playing a cis-acting role in a very early stage of the reactivation process. PMID:9227860

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

    SciTech Connect

    Vafai, A.; Wellish, M.; Devlin, M.; Gilden, D.H. ); Murray, R.S. Veterans Administration Medical Center, Denver, CO )

    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.

  8. Rapid and simultaneous detection of 6 types of human herpes virus (herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpes virus 6A/B, and human herpes virus 7) by multiplex PCR assay.

    PubMed

    Tanaka, Toshio; Kogawa, Kazuhiro; Sasa, Hidenori; Nonoyama, Shigeaki; Furuya, Kenichi; Sato, Kenji

    2009-10-01

    A multiplex PCR assay was developed that enabled the simultaneous detection of DNA from 6 types of human herpes virus, HSV-1/2, VZV, EBV, CMV, HHV-6A/B, and HHV-7, using appropriate primer sets and conventional PCR techniques and instruments, with PCR products for each type of virus designed to be easily distinguishable by size. Electropherograms obtained from conventional agarose gels showed that, for each type, the observed number of base pairs corresponded to the intended product and that bands were easily distinguishable from each other. A minimum of 20 copies of viral DNA in a reaction was sufficient to confirm the existence of each of the 6 types of human herpes virus. Comparison of the data obtained from this method and the data obtained from conventional TaqMan PCR using clinical specimens from various sources showed consistent results. The multiplex PCR method reported here for the detection and differentiation of human herpes viruses did not require special equipment or techniques such as hybridization analysis and sequencing analysis and, therefore, enabled us to easily and rapidly detect and identify the 6 types of human herpes virus using conventional methods.

  9. Herpes virus infection of the peripheral nervous system.

    PubMed

    Steiner, Israel

    2013-01-01

    Among the human herpes viruses, three are neurotropic and capable of producing severe neurological abnormalities: herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus (VZV). Both the acute, primary infection and the reactivation from the site of latent infection, the dorsal sensory ganglia, are associated with severe human morbidity and mortality. The peripheral nervous system is one of the major loci affected by these viruses. The present review details the virology and molecular biology underlying the human infection. This is followed by detailed description of the symtomatology, clinical presentation, diagnosis, course, therapy, and prognosis of disorders of the peripheral nervous system caused by these viruses.

  10. Peptide inhibitors against herpes simplex virus infections.

    PubMed

    Galdiero, Stefania; Falanga, Annarita; Tarallo, Rossella; Russo, Luigi; Galdiero, Emilia; Cantisani, Marco; Morelli, Giancarlo; Galdiero, Massimiliano

    2013-03-01

    Herpes simplex virus (HSV) is a significant human pathogen causing mucocutaneous lesions primarily in the oral or genital mucosa. Although acyclovir (ACV) and related nucleoside analogs provide successful treatment, HSV remains highly prevalent worldwide and is a major cofactor for the spread of human immunodeficiency virus. Encephalitis, meningitis, and blinding keratitis are among the most severe diseases caused by HSV. ACV resistance poses an important problem for immunocompromised patients and highlights the need for new safe and effective agents; therefore, the development of novel strategies to eradicate HSV is a global public health priority. Despite the continued global epidemic of HSV and extensive research, there have been few major breakthroughs in the treatment or prevention of the virus since the introduction of ACV in the 1980s. A therapeutic strategy at the moment not fully addressed is the use of small peptide molecules. These can be either modeled on viral proteins or derived from antimicrobial peptides. Any peptide that interrupts protein-protein or viral protein-host cell membrane interactions is potentially a novel antiviral drug and may be a useful tool for elucidating the mechanisms of viral entry. This review summarizes current knowledge and strategies in the development of synthetic and natural peptides to inhibit HSV infectivity.

  11. Zebrafish: modeling for herpes simplex virus infections.

    PubMed

    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.

  12. Zebrafish: Modeling for Herpes Simplex Virus Infections

    PubMed Central

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

    2014-01-01

    Abstract 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. PMID:24266790

  13. Vaccines for herpes simplex virus infections.

    PubMed

    Koelle, David M

    2006-02-01

    Infections with herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2) can have serious medical consequences. Although antiviral medications can suppress symptomatic disease, asymptomatic shedding and transmission, they neither cure nor alter the natural history of HSV infections. Manipulation of the immune response is one potential method to decrease disease burden. Current research on prophylactic and therapeutic vaccination approaches is discussed in this review, with a focus on compounds that have entered clinical trials or that display novel compositions or proposed mechanisms of action. One such vaccine is an alum and monophosphoryl lipid A-adjuvanted subunit glycoprotein D2 vaccine that has demonstrated activity in the prevention of HSV-2 infection and disease in HSV-uninfected women in a phase III clinical trial. Further confirmatory clinical trials of this vaccine are currently underway. Other vaccine formats also in development include attenuated live or replication-incompetent HSV-2 strains and technologies that target virus-specific CD8 T-cell responses.

  14. Replication-Competent Controlled Herpes Simplex Virus.

    PubMed

    Bloom, David C; Feller, Joyce; McAnany, Peterjon; Vilaboa, Nuria; Voellmy, Richard

    2015-10-01

    We present the development and characterization of a replication-competent controlled herpes simplex virus 1 (HSV-1). Replication-essential ICP4 and ICP8 genes of HSV-1 wild-type strain 17syn+ were brought under the control of a dually responsive gene switch. The gene switch comprises (i) a transactivator that is activated by a narrow class of antiprogestins, including mifepristone and ulipristal, and whose expression is mediated by a promoter cassette that comprises an HSP70B promoter and a transactivator-responsive promoter and (ii) transactivator-responsive promoters that drive the ICP4 and ICP8 genes. Single-step growth experiments in different cell lines demonstrated that replication of the recombinant virus, HSV-GS3, is strictly dependent on an activating treatment consisting of administration of a supraphysiological heat dose in the presence of an antiprogestin. The replication-competent controlled virus replicates with an efficiency approaching that of the wild-type virus from which it was derived. Essentially no replication occurs in the absence of activating treatment or if HSV-GS3-infected cells are exposed only to heat or antiprogestin. These findings were corroborated by measurements of amounts of viral DNA and transcripts of the regulated ICP4 gene and the glycoprotein C (gC) late gene, which was not regulated. Similar findings were made in experiments with a mouse footpad infection model. The alphaherpesviruses have long been considered vectors for recombinant vaccines and oncolytic therapies. The traditional approach uses vector backbones containing attenuating mutations that restrict replication to ensure safety. The shortcoming of this approach is that the attenuating mutations tend to limit both the immune presentation and oncolytic properties of these vectors. HSV-GS3 represents a novel type of vector that, when activated, replicates with the efficiency of a nonattenuated virus and whose safety is derived from deliberate, stringent regulation of

  15. Replication-Competent Controlled Herpes Simplex Virus

    PubMed Central

    Bloom, David C.; Feller, Joyce; McAnany, Peterjon; Vilaboa, Nuria

    2015-01-01

    ABSTRACT We present the development and characterization of a replication-competent controlled herpes simplex virus 1 (HSV-1). Replication-essential ICP4 and ICP8 genes of HSV-1 wild-type strain 17syn+ were brought under the control of a dually responsive gene switch. The gene switch comprises (i) a transactivator that is activated by a narrow class of antiprogestins, including mifepristone and ulipristal, and whose expression is mediated by a promoter cassette that comprises an HSP70B promoter and a transactivator-responsive promoter and (ii) transactivator-responsive promoters that drive the ICP4 and ICP8 genes. Single-step growth experiments in different cell lines demonstrated that replication of the recombinant virus, HSV-GS3, is strictly dependent on an activating treatment consisting of administration of a supraphysiological heat dose in the presence of an antiprogestin. The replication-competent controlled virus replicates with an efficiency approaching that of the wild-type virus from which it was derived. Essentially no replication occurs in the absence of activating treatment or if HSV-GS3-infected cells are exposed only to heat or antiprogestin. These findings were corroborated by measurements of amounts of viral DNA and transcripts of the regulated ICP4 gene and the glycoprotein C (gC) late gene, which was not regulated. Similar findings were made in experiments with a mouse footpad infection model. IMPORTANCE The alphaherpesviruses have long been considered vectors for recombinant vaccines and oncolytic therapies. The traditional approach uses vector backbones containing attenuating mutations that restrict replication to ensure safety. The shortcoming of this approach is that the attenuating mutations tend to limit both the immune presentation and oncolytic properties of these vectors. HSV-GS3 represents a novel type of vector that, when activated, replicates with the efficiency of a nonattenuated virus and whose safety is derived from deliberate

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

    SciTech Connect

    Straus, S.E. )

    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.

  17. Retargeting Strategies for Oncolytic Herpes Simplex Viruses.

    PubMed

    Campadelli-Fiume, Gabriella; Petrovic, Biljana; Leoni, Valerio; Gianni, Tatiana; Avitabile, Elisa; Casiraghi, Costanza; Gatta, Valentina

    2016-02-26

    Most of the oncolytic herpes simplex viruses (HSVs) exhibit a high safety profile achieved through attenuation. They carry defects in virulence proteins that antagonize host cell response to the virus, including innate response, apoptosis, authophagy, and depend on tumor cell proliferation. They grow robustly in cancer cells, provided that these are deficient in host cell responses, which is often the case. To overcome the attenuation limits, a strategy is to render the virus highly cancer-specific, e.g., by retargeting their tropism to cancer-specific receptors, and detargeting from natural receptors. The target we selected is HER-2, overexpressed in breast, ovarian and other cancers. Entry of wt-HSV requires the essential glycoproteins gD, gH/gL and gB. Here, we reviewed that oncolytic HSV retargeting was achieved through modifications in gD: the addition of a single-chain antibody (scFv) to HER-2 coupled with appropriate deletions to remove part of the natural receptors' binding sites. Recently, we showed that also gH/gL can be a retargeting tool. The insertion of an scFv to HER-2 at the gH N-terminus, coupled with deletions in gD, led to a recombinant capable to use HER-2 as the sole receptor. The retargeted oncolytic HSVs can be administered systemically by means of carrier cells-forcedly-infected mesenchymal stem cells. Altogether, the retargeted oncolytic HSVs are highly cancer-specific and their replication is not dependent on intrinsic defects of the tumor cells. They might be further modified to express immunomodulatory molecules.

  18. Retargeting Strategies for Oncolytic Herpes Simplex Viruses

    PubMed Central

    Campadelli-Fiume, Gabriella; Petrovic, Biljana; Leoni, Valerio; Gianni, Tatiana; Avitabile, Elisa; Casiraghi, Costanza; Gatta, Valentina

    2016-01-01

    Most of the oncolytic herpes simplex viruses (HSVs) exhibit a high safety profile achieved through attenuation. They carry defects in virulence proteins that antagonize host cell response to the virus, including innate response, apoptosis, authophagy, and depend on tumor cell proliferation. They grow robustly in cancer cells, provided that these are deficient in host cell responses, which is often the case. To overcome the attenuation limits, a strategy is to render the virus highly cancer-specific, e.g., by retargeting their tropism to cancer-specific receptors, and detargeting from natural receptors. The target we selected is HER-2, overexpressed in breast, ovarian and other cancers. Entry of wt-HSV requires the essential glycoproteins gD, gH/gL and gB. Here, we reviewed that oncolytic HSV retargeting was achieved through modifications in gD: the addition of a single-chain antibody (scFv) to HER-2 coupled with appropriate deletions to remove part of the natural receptors’ binding sites. Recently, we showed that also gH/gL can be a retargeting tool. The insertion of an scFv to HER-2 at the gH N-terminus, coupled with deletions in gD, led to a recombinant capable to use HER-2 as the sole receptor. The retargeted oncolytic HSVs can be administered systemically by means of carrier cells-forcedly-infected mesenchymal stem cells. Altogether, the retargeted oncolytic HSVs are highly cancer-specific and their replication is not dependent on intrinsic defects of the tumor cells. They might be further modified to express immunomodulatory molecules. PMID:26927159

  19. Latent Herpes Viruses Reactivation in Astronauts

    NASA Technical Reports Server (NTRS)

    Mehta, Satish K.; Pierson, Duane L.

    2008-01-01

    Space flight has many adverse effects on human physiology. Changes in multiple systems, including the cardiovascular, musculoskeletal, neurovestibular, endocrine, and immune systems have occurred (12, 32, 38, 39). Alterations in drug pharmacokinetics and pharmacodynamics (12), nutritional needs (31), renal stone formation (40), and microbial flora (2) have also been reported. Evidence suggests that the magnitude of some changes may increase with time in space. A variety of changes in immunity have been reported during both short (.16 days) and long (>30 days) space missions. However, it is difficult to determine the medical significance of these immunological changes in astronauts. Astronauts are in excellent health and in superb physical condition. Illnesses in astronauts during space flight are not common, are generally mild, and rarely affect mission objectives. In an attempt to clarify this issue, we identified the latent herpes viruses as medically important indicators of the effects of space flight on immunity. This chapter demonstrates that space flight leads to asymptomatic reactivation of latent herpes viruses, and proposes that this results from marked changes in neuroendocrine function and immunity caused by the inherent stressfullness of human space flight. Astronauts experience uniquely stressful environments during space flight. Potential stressors include confinement in an unfamiliar, crowded environment, isolation, separation from family, anxiety, fear, sleep deprivation, psychosocial issues, physical exertion, noise, variable acceleration forces, increased radiation, and others. Many of these are intermittent and variable in duration and intensity, but variable gravity forces (including transitions from launch acceleration to microgravity and from microgravity to planetary gravity) and variable radiation levels are part of each mission and contribute to a stressful environment that cannot be duplicated on Earth. Radiation outside the Earth

  20. 75 FR 59611 - Microbiology Devices; Reclassification of Herpes Simplex Virus Types 1 and 2 Serological Assays...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... Herpes Simplex Virus Types 1 and 2 Serological Assays; Confirmation of Effective Date AGENCY: Food and... corrects the regulation classifying herpes simplex virus (HSV) serological assays by removing the reference...

  1. Multiplex PCR for identification of herpes virus infections in adolescents.

    PubMed

    Durzyńska, Julia; Pacholska-Bogalska, Joanna; Kaczmarek, Maria; Hanć, Tomasz; Durda, Magdalena; Skrzypczak, Magdalena; Goździcka-Józefiak, Anna

    2011-02-01

    The aim of the study was to develop a multiplex PCR (mPCR) for a rapid and simultaneous detection of herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), and human cytomegalovirus (HCMV) DNA in squamous oral cells obtained from adolescents. Accuracy of the method was tested in a group of 513 adolescents, almost 11% of subjects were positive for infection with herpes viruses. Correlations with gender, age, and place of residence were sought. A similar incidence of HSV-2 and HCMV was found (4.3% and 5.4%, respectively) and the incidence of HSV-1 was the lowest (1%) in the study group. Conversely to HSV-2, HCMV was detected mostly in the youngest individuals. The same occurrence of all viruses was observed in boys and girls. The mPCR method described is suggested as a useful tool for epidemiologic studies of active herpes infections.

  2. Herpes simplex virus encephalitis during treatment with etanercept.

    PubMed

    Crusio, Robbert H J; Singson, Stephanie V; Haroun, Faysal; Mehta, Hetal H; Parenti, David M

    2014-02-01

    Tumor necrosis factor alpha (TNF-α) inhibitors are widely used for the treatment of various inflammatory conditions. They are associated with an increased risk for infections. We report a case of herpes simplex virus type 1 (HSV-1) encephalitis in a patient receiving etanercept and review the literature on TNF-α and TNF-α inhibitors, and their importance in the pathophysiology of herpes simplex encephalitis.

  3. Herpes simplex virus-induced cardiomyopathy successfully treated with acyclovir.

    PubMed

    Kuchynka, Petr; Palecek, Tomas; Hrbackova, Hana; Vitkova, Ivana; Simek, Stanislav; Nemecek, Eduard; Aster, Viktor; Louch, William E; Aschermann, Michael; Linhart, Ales

    2010-10-01

    Inflammatory dilated cardiomyopathy (DCMi) represents an acquired form of dilated cardiomyopathy. Viral infection is the most common cause of DCMi. In contrast with other cardiotropic viruses, herpes simplex virus (HSV) is a very rare finding in endomyocardial biopsies of patients with dilated cardiomyopathy. We report a case of HSV-induced cardiomyopathy successfully treated with acyclovir.

  4. Prevalence of Herpes Simplex Virus Antibodies in Dental Students.

    ERIC Educational Resources Information Center

    Rodu, Brad; And Others

    1992-01-01

    A study of 125 sophomore preclinical dental students found that these young professionals, because of having a low prevalence of herpes simplex virus (HSV) antibodies, are at risk for acquiring a primary HSV infection when treating HSV positive patients and should take precautions to avoid virus transmission. (MSE)

  5. Prevalence of Herpes Simplex Virus Antibodies in Dental Students.

    ERIC Educational Resources Information Center

    Rodu, Brad; And Others

    1992-01-01

    A study of 125 sophomore preclinical dental students found that these young professionals, because of having a low prevalence of herpes simplex virus (HSV) antibodies, are at risk for acquiring a primary HSV infection when treating HSV positive patients and should take precautions to avoid virus transmission. (MSE)

  6. Improving immunogenicity and efficacy of vaccines for genital herpes containing herpes simplex virus glycoprotein D.

    PubMed

    Awasthi, Sita; Shaw, Carolyn; Friedman, Harvey

    2014-12-01

    No vaccines are approved for prevention or treatment of genital herpes. The focus of genital herpes vaccine trials has been on prevention using herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) alone or combined with glycoprotein B. These prevention trials did not achieve their primary end points. However, subset analyses reported some positive outcomes in each study. The most recent trial was the Herpevac Trial for Women that used gD2 with monophosphoryl lipid A and alum as adjuvants in herpes simplex virus type 1 (HSV-1) and HSV-2 seronegative women. Unexpectedly, the vaccine prevented genital disease by HSV-1 but not HSV-2. Currently, HSV-1 causes more first episodes of genital herpes than HSV-2, highlighting the importance of protecting against HSV-1. The scientific community is conflicted between abandoning vaccine efforts that include gD2 and building upon the partial successes of previous trials. We favor building upon success and present approaches to improve outcomes of gD2-based subunit antigen vaccines.

  7. Herpes simplex virus lymphadenitis: the elusive doppelganger in immunocompromised patients.

    PubMed

    Cases, Margaret; Leduc, Charles; Farmer, Patricia L; Richardson, Susan E; Zoutman, Dick E

    2014-01-01

    Herpes simplex virus has protean manifestations and is an important cause of morbidity in the immunocompromised host. We report a case of recurrent lymphadenopathy and rash in a patient with chronic lymphocytic leukemia. The elusive clinical diagnosis eventually required core biopsy of a lymph node with immunohistochemistry and confirmation by polymerase chain reaction. This case illustrates the challenging clinical and laboratory diagnosis of herpes simplex virus lymphadenitis and the need to maintain a high index of suspicion for infection when treating an immunocompromised patient with unusual and/or persistent symptoms.

  8. Human herpes simplex virus: life cycle and development of inhibitors.

    PubMed

    Kukhanova, M K; Korovina, A N; Kochetkov, S N

    2014-12-01

    WHO reports that 90% of human population is infected by different types of herpesviruses, which develop latency or cause oral and genital herpes, conjunctivitis, eczema herpeticum, and other diseases. Herpesvirus almost always accompanies HIV-infection and complicates AIDS treatment. Herpes simplex virus type 1 is one of the most wide spread viruses from the Herpesviridae family. HSV virion, genome structure, replication mechanisms, antiherpes drug development strategies, including design of prodrugs, and mutations causing ACV-resistance in clinical HSV isolates are discussed in this review.

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

    PubMed

    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.

  10. Engineered Herpes Simplex Viruses for the Treatment of Malignant Peripheral Nerve Sheath Tumors

    DTIC Science & Technology

    2012-09-01

    AD_________________ Award Number: W81XWH-11-1-0498 TITLE: Engineered Herpes Simplex Viruses for the...August 2012 4. TITLE AND SUBTITLE Engineered Herpes Simplex Viruses for the Treatment of Malignant Peripheral Nerve Sheath Tumors 5a. CONTRACT NUMBER...for each blot. Glyco-protein D is produced at extraordinarily high levels by our herpes simplex virus, and thus, it is quite common in herpes simplex

  11. Bell's palsy and herpes simplex virus.

    PubMed

    Schirm, J; Mulkens, P S

    1997-11-01

    Bell's palsy, which is defined as idiopathic peripheral facial paralysis of sudden onset, accounts for > 50% of all cases of facial paralysis. Different theories on the etiology of Bell's palsy have been proposed and investigated. Various clinical studies have suggested an etiological link between Bell's palsy and herpes simplex virus (HSV). In addition, animal experiments have shown the ability of HSV to induce facial paralysis. In our opinion, the possible link between Bell's palsy and HSV can only be explored properly by studying the human facial nerve, and especially the geniculate ganglion itself. Different groups have tried to detect hypothetically reactivated and hypothetically latent HSV in the facial nerves of Bell's palsy patients and control patients, respectively. The isolation of infectious HSV from facial nerve tissue by conventional cell culture methods appeared to be very difficult, also when Bell's palsy patients were tested. Instead, modern molecular methods, such as in situ hybridization and the polymerase chain reaction (PCR) could easily detect HSV DNA in geniculate ganglia. The detection of HSV-specific latency-associated transcripts in the ganglia of control patients provided further evidence for the hypothetically latent state of HSV in the geniculate ganglia in these patients. Recent PCR experiments performed by a Japanese group strongly suggest that the area adjacent to the geniculate ganglia does not usually contain any HSV at all, except in patients with Bell's palsy. This well-controlled study provides conclusive evidence that reactivation of HSV genomes from the geniculate ganglia is the most important cause of Bell's palsy. Consequently, it has been suggested that "Bell's palsy" be renamed as "herpetic facial paralysis".

  12. Herpes Simplex Virus 2 ICP0− Mutant Viruses Are Avirulent and Immunogenic: Implications for a Genital Herpes Vaccine

    PubMed Central

    Halford, William P.; Püschel, Ringo; Rakowski, Brandon

    2010-01-01

    Herpes simplex virus 1 (HSV-1) ICP0− mutants are interferon-sensitive, avirulent, and elicit protective immunity against HSV-1 (Virol J, 2006, 3:44). If an ICP0− mutant of herpes simplex virus 2 (HSV-2) exhibited similar properties, such a virus might be used to vaccinate against genital herpes. The current study was initiated to explore this possibility. Several HSV-2 ICP0− mutant viruses were constructed and evaluated in terms of three parameters: i. interferon-sensitivity; ii. virulence in mice; and iii. capacity to elicit protective immunity against HSV-2. One ICP0− mutant virus in particular, HSV-2 0ΔNLS, achieved an optimal balance between avirulence and immunogenicity. HSV-2 0ΔNLS was interferon-sensitive in cultured cells. HSV-2 0ΔNLS replicated to low levels in the eyes of inoculated mice, but was rapidly repressed by an innate, Stat 1-dependent host immune response. HSV-2 0ΔNLS failed to spread from sites of inoculation, and hence produced only inapparent infections. Mice inoculated with HSV-2 0ΔNLS consistently mounted an HSV-specific IgG antibody response, and were consistently protected against lethal challenge with wild-type HSV-2. Based on their avirulence and immunogenicity, we propose that HSV-2 ICP0− mutant viruses merit consideration for their potential to prevent the spread of HSV-2 and genital herpes. PMID:20808928

  13. Herpes simplex virus 2 ICP0 mutant viruses are avirulent and immunogenic: implications for a genital herpes vaccine.

    PubMed

    Halford, William P; Püschel, Ringo; Rakowski, Brandon

    2010-08-17

    Herpes simplex virus 1 (HSV-1) ICP0(-) mutants are interferon-sensitive, avirulent, and elicit protective immunity against HSV-1 (Virol J, 2006, 3:44). If an ICP0(-) mutant of herpes simplex virus 2 (HSV-2) exhibited similar properties, such a virus might be used to vaccinate against genital herpes. The current study was initiated to explore this possibility. Several HSV-2 ICP0(-) mutant viruses were constructed and evaluated in terms of three parameters: i. interferon-sensitivity; ii. virulence in mice; and iii. capacity to elicit protective immunity against HSV-2. One ICP0(-) mutant virus in particular, HSV-2 0DeltaNLS, achieved an optimal balance between avirulence and immunogenicity. HSV-2 0DeltaNLS was interferon-sensitive in cultured cells. HSV-2 0DeltaNLS replicated to low levels in the eyes of inoculated mice, but was rapidly repressed by an innate, Stat 1-dependent host immune response. HSV-2 0DeltaNLS failed to spread from sites of inoculation, and hence produced only inapparent infections. Mice inoculated with HSV-2 0DeltaNLS consistently mounted an HSV-specific IgG antibody response, and were consistently protected against lethal challenge with wild-type HSV-2. Based on their avirulence and immunogenicity, we propose that HSV-2 ICP0(-) mutant viruses merit consideration for their potential to prevent the spread of HSV-2 and genital herpes.

  14. The challenge of developing a herpes simplex virus 2 vaccine

    PubMed Central

    Dropulic, Lesia K; Cohen, Jeffrey I

    2013-01-01

    HSV infections are prevalent worldwide. A vaccine to prevent genital herpes would have a significant impact on this disease. Several vaccines have shown promise in animal models; however, so far these have not been successful in human clinical studies. Prophylactic HSV vaccines to prevent HSV infection or disease have focused primarily on eliciting antibody responses. Potent antibody responses are needed to result in sufficiently high levels of virus-specific antibody in the genital tract. Therapeutic vaccines that reduce recurrences need to induce potent T-cell responses at the site of infection. With the increasing incidence of HSV-1 genital herpes, an effective herpes vaccine should protect against both HSV-1 and HSV-2. Novel HSV vaccines, such as replication-defective or attenuated viruses, have elicited humoral and cellular immune responses in preclinical studies. These vaccines and others hold promise in future clinical studies. PMID:23252387

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

    PubMed Central

    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

  16. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal...

  17. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal...

  18. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal...

  19. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal...

  20. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal...

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

    PubMed

    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.

  2. [Phosphoramidate derivatives of acyclovir--herpes virus replication inhibitors].

    PubMed

    Zakirova, N F; Shipitsyn, A V; Ias'ko, M V; Kochetkov, S N

    2011-01-01

    A number of new phosphoramidates of acyclovir--compounds of interest as anti-virals against resistant strains of virus herpes was synthesized. Several methods of synthesis of these compounds were suggested. Optimal method appeared to be the obtaining of phosphoramidates through the phosphomonocloride with its subsequent treatment with various amines. Two compounds have shown moderate activity against HSV-1.

  3. Genome Sequence of Herpes Simplex Virus 1 Strain SC16

    PubMed Central

    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. Herpes simplex virus oesophagitis in a pregnant woman.

    PubMed

    Remmelts, H H F; van den Brink, J-W; Laan, R; Bac, D-J

    2011-02-01

    Herpes simplex virus (HSV) oesophagitis is well described in immunocompromised patients. In immunocompetent individuals HSV oesophagitis is rare. We present a case of HSV oesophagitis in a pregnant woman. A possible explanation for HSV oesophagitis during pregnancy is the decreased cellular immunity, leading to an increased frequency and severity of viral infections. Antiviral therapy is advocated in pregnancy.

  5. Management of neonatal herpes simplex virus infection and exposure.

    PubMed

    Pinninti, Swetha G; Kimberlin, David W

    2014-05-01

    Neonatal herpes simplex virus (HSV) infections are rare but are associated with significant morbidity and mortality. Advances in diagnostic modalities to identify these infants, as well as the development of safe and effective antiviral therapy, have revolutionised the management of affected infants. This review will summarise the epidemiology of neonatal HSV infections and discuss the management of infants with HSV exposure and infection.

  6. The mortality of neonatal herpes simplex virus infection.

    PubMed

    Lopez-Medina, Eduardo; Cantey, Joseph B; Sánchez, Pablo J

    2015-06-01

    This retrospective study characterized the clinical course of 13 neonates who died with herpes simplex virus infection from 2001 to 2011, representing a 26% case-fatality rate. Fatal disease developed at ≤ 48 hours of age in one-third of infants, was mostly disseminated disease, and occurred despite early administration of high-dose acyclovir therapy.

  7. Human Herpes Simplex Virus Type 1 in Confiscated Gorilla

    PubMed Central

    Oxford, Kristie L.; Gardner-Roberts, David; Kinani, Jean-Felix; Spelman, Lucy; Barry, Peter A.; Cranfield, Michael R.; Lowenstine, Linda J.

    2014-01-01

    In 2007, we detected human herpes simplex virus type 1, which caused stomatitis, in a juvenile confiscated eastern lowland gorilla (Gorilla beringei graueri) that had a high degree of direct contact with human caretakers. Our findings confirm that pathogens can transfer between nonhuman primate hosts and humans. PMID:25341185

  8. Treatment of mucocutaneous presentations of herpes simplex virus infections.

    PubMed

    Nikkels, Arjen F; Pièrard, Gérald E

    2002-01-01

    Infections by herpes simplex virus (HSV) types I and II are diverse and quite frequent. After primary infection, the virus establishes a life-long latency in the sensory ganglia and recrudescences may occur at an unpredictable rate. Recurrent labial and genital herpes infections represent the majority of clinical manifestations of HSV infections. Their management is currently well established using evidence-based medicine data. Primary labial herpes is generally not treated with antivirals in otherwise healthy children, although intravenous aciclovir may be offered in severe primary infections, particularly in the immunocompromised patient. The decision whether or not to treat recurrent labial herpes should be evaluated individually and depends on the frequency and severity of relapses, the impairment of the quality of life, and the cost of therapy. Patients with mild disease may benefit from topical therapy, and those with severe and frequent recurrences may be considered for intermittent or long-term oral antiviral therapy. Primary genital herpes is treated with oral or intravenous antivirals, depending on the severity of the infection and associated symptoms. Recurrent genital herpes can be managed with episodic short courses of oral antivirals in patients whose recurrences are moderate to severe and rare, and have a clear prodrome. Patients with >5 episodes/year, severe recurrences or unrecognisable prodromes may be best managed with long-term suppressive antiviral prophylaxis. HSV is also responsible for a variety of other clinical manifestations, including herpetic whitlow, neonatal infection, disseminated and atypical cutaneous infections, traumatic herpes, eczema herpeticum, and HSV-associated erythema multiforme. HSV infection may also represent a complication following cosmetic procedures of the oro-facial region, surgical and dental interventions, sun exposure and burns. Precise treatment guidelines for these HSV infections are not firmly established.

  9. Pediatric herpes simplex virus infections: an evidence-based approach to treatment.

    PubMed

    Sanders, Jennifer E; Garcia, Sylvia E

    2014-01-01

    Herpes simplex virus is a common virus that causes a variety of clinical presentations ranging from mild to life-threatening. Orolabial and genital herpes are common disorders that can often be managed in an outpatient setting; however, some patients do present to the emergency department with those conditions, and emergency clinicians should be aware of possible complications in the pediatric population. Neonatal herpes is a rare disorder, but prompt recognition and initiation of antiviral therapy is imperative, as the morbidity and mortality of the disease is high. Herpes encephalitis is an emergency that also requires a high index of suspicion to diagnose. Herpes simplex virus is also responsible for a variety of other clinical presentations, including herpes gladiatorum, herpetic whitlow, eczema herpeticum, and ocular herpes. This issue reviews the common clinical presentations of the herpes simplex virus, the life-threatening infections that require expedient identification and management, and recommended treatment regimens.

  10. Herpes virus seroepidemiology in the adult Swedish population.

    PubMed

    Olsson, Jan; Kok, Eloise; Adolfsson, Rolf; Lövheim, Hugo; Elgh, Fredrik

    2017-01-01

    Herpes viruses establish a life-long latency and can cause symptoms during both first-time infection and later reactivation. The aim of the present study was to describe the seroepidemiology of Herpes simplex type 1 (HSV1), Herpes simplex type 2 (HSV2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV) and Human herpes virus type 6 (HHV6) in an adult Swedish population (35-95 years of age). Presence of antibodies against the respective viruses in serum from individuals in the Betula study was determined with an enzyme-linked immunosorbent assay (ELISA). Singular samples from 535 persons (53.9% women, mean age at inclusion 62.7 ± 14.4 years) collected 2003-2005 were analyzed for the five HHVs mentioned above. In addition, samples including follow-up samples collected 1988-2010 from 3,444 persons were analyzed for HSV. Prevalence of HSV1 was 79.4%, HSV2 12.9%, CMV 83.2%, VZV 97.9%, and HHV6 97.5%. Herpes virus infections were more common among women (p = 0.010) and a lower age-adjusted HSV seroprevalence was found in later birth cohorts (p < 0.001). The yearly incidence of HSV infection was estimated at 14.0/1000. Women are more often seropositive for HHV, especially HSV2. Age-adjusted seroprevalence for HSV was lower in later birth cohorts indicating a decreasing childhood and adolescent risk of infection.

  11. Persistent infection with neurotropic herpes viruses and cognitive impairment.

    PubMed

    Watson, A M M; Prasad, K M; Klei, L; Wood, J A; Yolken, R H; Gur, R C; Bradford, L D; Calkins, M E; Richard, J; Edwards, N; Savage, R M; Allen, T B; Kwentus, J; McEvoy, J P; Santos, A B; Wiener, H W; Go, R C P; Perry, R T; Nasrallah, H A; Gur, R E; Devlin, B; Nimgaonkar, V L

    2013-05-01

    Herpes virus infections can cause cognitive impairment during and after acute encephalitis. Although chronic, latent/persistent infection is considered to be relatively benign, some studies have documented cognitive impairment in exposed persons that is untraceable to encephalitis. These studies were conducted among schizophrenia (SZ) patients or older community dwellers, among whom it is difficult to control for the effects of co-morbid illness and medications. To determine whether the associations can be generalized to other groups, we examined a large sample of younger control individuals, SZ patients and their non-psychotic relatives (n=1852). Method Using multivariate models, cognitive performance was evaluated in relation to exposures to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV), controlling for familial and diagnostic status and sociodemographic variables, including occupation and educational status. Composite cognitive measures were derived from nine cognitive domains using principal components of heritability (PCH). Exposure was indexed by antibodies to viral antigens. PCH1, the most heritable component of cognitive performance, declines with exposure to CMV or HSV-1 regardless of case/relative/control group status (p = 1.09 × 10-5 and 0.01 respectively), with stronger association with exposure to multiple herpes viruses (β = -0.25, p = 7.28 × 10-10). There were no significant interactions between exposure and group status. Latent/persistent herpes virus infections can be associated with cognitive impairments regardless of other health status.

  12. The molecular basis of herpes simplex virus latency.

    PubMed

    Nicoll, Michael P; Proença, João T; Efstathiou, Stacey

    2012-05-01

    Herpes simplex virus type 1 is a neurotropic herpesvirus that establishes latency within sensory neurones. Following primary infection, the virus replicates productively within mucosal epithelial cells and enters sensory neurones via nerve termini. The virus is then transported to neuronal cell bodies where latency can be established. Periodically, the virus can reactivate to resume its normal lytic cycle gene expression programme and result in the generation of new virus progeny that are transported axonally back to the periphery. The ability to establish lifelong latency within the host and to periodically reactivate to facilitate dissemination is central to the survival strategy of this virus. Although incompletely understood, this review will focus on the mechanisms involved in the regulation of latency that centre on the functions of the virus-encoded latency-associated transcripts (LATs), epigenetic regulation of the latent virus genome and the molecular events that precipitate reactivation.

  13. Herpes Simplex Virus Infections of the Central Nervous System.

    PubMed

    Whitley, Richard J

    2015-12-01

    This article summarizes knowledge of herpes simplex virus (HSV) infections of the central nervous system (CNS). Disease pathogenesis, detection of DNA polymerase chain reaction (PCR) for diagnosis and prognosis, and approaches to therapy warrant consideration. HSV infection of the CNS is one of few treatable viral diseases. Clinical trials indicate that outcome following neonatal herpes simplex virus type 2 (HSV-2) infections of the CNS is significantly improved when 6 months of suppressive oral acyclovir therapy follows IV antiviral therapy. In contrast, herpes simplex virus type 1 (HSV-1) infections of the brain do not benefit from extended oral antiviral therapy. This implies a difference in disease pathogenesis between HSV-2 and HSV-1 infections of the brain. PCR detection of viral DNA in the CSF is the gold standard for diagnosis. Use of PCR is now being adopted as a basis for determining the duration of therapy in the newborn. HSV infections are among the most common encountered by humans; seropositivity occurs in 50% to 90% of adult populations. Herpes simplex encephalitis, however, is an uncommon result of this infection. Since no new antiviral drugs have been introduced in nearly 3 decades, much effort has focused on learning how to better use acyclovir and how to use existing databases to establish earlier diagnosis.

  14. Immune inhibition of virus release from herpes simplex virus-infected cells by human sera.

    PubMed

    Shariff, D M; Hallworth, J; Desperbasques, M; Buchan, A; Skinner, G R

    1988-01-01

    Human sera contain antibody (IVR antibody) which will inhibit the release of herpes simplex virus type 1 from virus-infected cells. This antibody activity was removed by adsorption of sera with virus-infected cell extract. There was a positive correlation between IVR and neutralizing antibody activity, particularly when measured by augmented neutralization test; measurement of IVR antibody was equally as sensitive as measurement of neutralizing antibody by augmented neutralization test. IVR antibody levels provided indication of a history of recurrent herpes labialis, the pattern of antibody response following primary herpetic infection, and indication of response to Skinner herpes vaccine in human subjects. It is suggested that consideration should be given to measurement of IVR antibody in both clinical and epidemiological studies of herpes and other virus infections.

  15. Immune inhibition of virus release from herpes simplex virus-infected cells.

    PubMed

    Skinner, G R; Mushi, E Z; Whitney, J E

    By treatment of herpes simplex virus-infected cells with virus antiserum with or without complement, the yield of infectious extracellular virus was significantly reduced. This was shown to be due to an immune alteration of the cell membrane which inhibited release of virus particles from the infected cells and not due to neutralization; both type-common and type-specific antigens of herpes simplex virus were involved. The phenomenon was also evident with antisera directed against cell determinants. The experimental findings are presented and their significance in the immunological defense mechanisms of the body and in viral immunotherapy is discussed.

  16. The molecular basis of herpes simplex virus latency

    PubMed Central

    Nicoll, Michael P; Proença, João T; Efstathiou, Stacey

    2012-01-01

    Herpes simplex virus type 1 is a neurotropic herpesvirus that establishes latency within sensory neurones. Following primary infection, the virus replicates productively within mucosal epithelial cells and enters sensory neurones via nerve termini. The virus is then transported to neuronal cell bodies where latency can be established. Periodically, the virus can reactivate to resume its normal lytic cycle gene expression programme and result in the generation of new virus progeny that are transported axonally back to the periphery. The ability to establish lifelong latency within the host and to periodically reactivate to facilitate dissemination is central to the survival strategy of this virus. Although incompletely understood, this review will focus on the mechanisms involved in the regulation of latency that centre on the functions of the virus-encoded latency-associated transcripts (LATs), epigenetic regulation of the latent virus genome and the molecular events that precipitate reactivation. This review considers current knowledge and hypotheses relating to the mechanisms involved in the establishment, maintenance and reactivation herpes simplex virus latency. PMID:22150699

  17. Oncolytic virus therapy using genetically engineered herpes simplex viruses.

    PubMed

    Todo, Tomoki

    2008-01-01

    Genetically engineered, conditionally replicating herpes simplex viruses type 1 (HSV-1) are promising therapeutic agents for cancer. They can replicate in situ, spread, and exhibit oncolytic activity via a direct cytocidal effect. In addition, oncolytic HSV-1 can transfer and express foreign genes in host cells. The phase I clinical study with G207, a double-mutated HSV-1, in recurrent malignant glioma patients has shown that oncolytic HSV-1 can be safely administered into human brains. The therapeutic benefits of oncolytic HSV-1 depend on the extent of both intratumoral viral replication and induction of host antitumor immune responses. We develop new-generation oncolytic HSV-1 by enhancing these properties while retaining the safety features. G47delta was created from G207 by introducing another genetic mutation. Compared with G207, G47delta showed 1) better stimulation of human antitumor immune cells, 2) better growth properties leading to higher virus yields and increased cytopathic effect in vitro, 3) better antitumor efficacy in both immuno-competent and -incompetent animals, and 4) preserved safety in the brain of HSV-1-sensitive mice. Preparation is under way for a clinical trial using G47delta in progressive glioblastoma patients. G47delta is also suited as a backbone vector for expressing foreign molecules. Using bacterial artificial chromosome and two DNA recombinases, we have created an "armed" oncolytic HSV-1 generation system that allows insertion of transgene(s) into the genome of G47delta in a rapid and accurate manner. We found that expression of immunostimulatory molecules can significantly enhance the antitumor efficacy of G47delta. Based on these advances, we anticipate that oncolytic virus therapy using oncolytic HSV-1 will soon be established as an important modality of cancer treatment.

  18. Evasion of early antiviral responses by herpes simplex viruses.

    PubMed

    Suazo, Paula A; Ibañez, Francisco J; Retamal-Díaz, Angello R; Paz-Fiblas, Marysol V; Bueno, Susan M; Kalergis, Alexis M; González, Pablo A

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency.

  19. Evasion of Early Antiviral Responses by Herpes Simplex Viruses

    PubMed Central

    Suazo, Paula A.; Ibañez, Francisco J.; Retamal-Díaz, Angello R.; Paz-Fiblas, Marysol V.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency. PMID:25918478

  20. A virus-particle vaccine prepared from bovine mammillitis virus against herpes genitalis.

    PubMed

    Skinner, G R; Buchan, A; Davies, J; Durham, J; Castrucci, G

    1991-01-01

    A vaccine against herpes genitalis was prepared from the extracellular virus particles from baby hamster kidney cells infected with bovine mammillitis virus (BMV) strain "Allerton". The virus was inactivated by formaldehyde followed by ultracentrifugation to concentrate the virus particles and eliminate formaldehyde to an acceptable concentration for immunisation of human subjects. The vaccine was cross antigenic and cross immunogenic with herpes simplex virus type 1. Thirty-four consorts at high risk of herpes genitalis were immunised with two or three doses each containing 10(9) virus particles equialent to approx. 150 micrograms protein. There has been no evidence of local or general side effect in a follow-up period of over 100 patient years. The immunogenicity and protective efficacy of this vaccine in human subjects will be investigated in a double-blind placebo-controlled trial.

  1. Heat shock and herpes virus: enhanced reactivation without untargeted mutagenesis

    SciTech Connect

    Lytle, C.D.; Carney, P.G.

    1988-01-01

    Enhanced reactivation of Ultraviolet-irradiated virus has been reported to occur in heat-shocked host cells. Since enhanced virus reactivation is often accompanied by untargeted mutagenesis, we investigated whether such mutagenesis would occur for herpes simplex virus (HSV) in CV-1 monkey kidney cells subjected to heat shock. In addition to expressing enhanced reactivation, the treated cells were transiently more susceptible to infection by unirradiated HSV. No mutagenesis of unirradiated HSV was found whether infection occurred at the time of increased susceptibility to infection or during expression of enhanced viral reactivation.

  2. The equine herpes virus 4 thymidine kinase is a better suicide gene than the human herpes virus 1 thymidine kinase.

    PubMed

    Loubière, L; Tiraby, M; Cazaux, C; Brisson, E; Grisoni, M; Zhao-Emonet, J; Tiraby, G; Klatzmann, D

    1999-09-01

    The herpes simplex virus type 1 thymidine kinase suicide gene (HSV1tk) together with ganciclovir (GCV) have been successfully used for in vivo treatment of various experimental tumors, and many clinical trials using this system have been launched. With the aim to improve this therapeutic system, we compared the potential efficacy of different herpes virus derived thymidine kinases (HSV1, varicella-zoster virus, equine herpes virus type-4 and Epstein-Barr virus) as suicide genes in association with the nucleoside analogs acyclovir, ganciclovir and bromovinyldeoxyur- idine. Using various murine and human cell lines expressing these viral tk, we show that HSV1- and EHV4tk are the more efficient suicide genes for the different nucleoside analogs tested. Moreover, EHV4tk expressing murine and human cells were three- to 12-fold more sensitive to GCV than HSV1tk expressing cells. This was correlated with the presence of five-fold higher amounts of the toxic triphosphated-GCV in EHV4- versus HSV1tk expressing cells. Altogether, these experiments underline the potential advantages of the EHV4tk as a suicide gene.

  3. Corneal donor infection by herpes simplex virus: herpes simplex virus DNA in donor corneas.

    PubMed

    Cleator, G M; Klapper, P E; Dennett, C; Sullivan, A L; Bonshek, R E; Marcyniuk, B; Tullo, A B

    1994-07-01

    Three corneoscleral discs (from two donors) underwent subtotal endothelial loss during routine "long-term" organ culture storage. Laboratory studies of these corneas revealed evidence of herpes simplex virus (HSV) infection. The fellow cornea from one of the donors had been issued for transplant to a patient with keratoconus. Deterioration of the graft was noted 5 days after surgery; the disc was removed at 2 months and was shown to be infected with HSV. In an experiment designed to simulate initial "cleansing" of donor globes, 0.1% polyvinylpyrolidone-iodine protected cells from infection with HSV. It was concluded that the detection of HSV in these corneas could not be explained by external contamination of the ocular surface. Furthermore, culture of conjunctival and pharangeal swabs taken from 47 consecutive donors confirmed that HSV is rarely isolated at or around the time of death. Five pairs of donor corneas destined for use in transplantation were selected at random and investigated for the presence of HSV. HSV DNA was detected by polymerase chain reaction (PCR) in tissue from two of the corneal donors. Sequential stepwise sectioning suggested that HSV DNA when present was distributed in discrete foci within the cornea. These observations suggest that HSV infection may be a cause of severe endothelial loss during corneal organ culture and possibly provide an explanation for some "failures" of corneal grafting.

  4. Human herpes viruses in burn patients: A systematic review.

    PubMed

    Wurzer, Paul; Guillory, Ashley; Parvizi, Daryousch; Clayton, Robert P; Branski, Ludwik K; Kamolz, Lars-P; Finnerty, Celeste C; Herndon, David N; Lee, Jong O

    2017-02-01

    The contribution of human herpes viruses, including herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV) to morbidity and mortality after burns remains controversial. This systematic review was undertaken to assess evidence of herpes virus-related morbidity and mortality in burns. PubMed, Ovid, and Web of Science were searched to identify studies of HSV, CMV, or VZV infections in burn patients. Exclusion criteria included: A level of evidence (LoE) of IV or V; nonhuman in vivo studies; and non-English articles. There was no limitation by publication date. Fifty articles were subjected to full-text analysis. Of these, 18 had LoE between I-III and were included in the final review (2 LoE I, 16 LoE II-III). Eight had a prospective study design, 9 had a retrospective study design, and 1 included both. No direct evidence linked CMV and HSV infection with increased morbidity and mortality in burns. Following burn, CMV reactivation was more common than a primary CMV infection. Active HSV infection impaired wound healing but was not directly correlated to mortality. Infections with VZV are rare after burns but when they occur, VZV infections were associated with severe complications including mortality. The therapeutic effect of antiviral agents administered after burns warrants investigation via prospective randomized controlled trials. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  5. Herpes simplex virus: isolation, cytopathological characterization and antiviral sensitivity*

    PubMed Central

    Nozawa, Carlos; Hattori, Lilian Yumi; Galhardi, Ligia Carla Faccin; Lopes, Nayara; Bomfim, Wesley Andrade; de Cândido, Ligyana Korki; de Azevedo, Elbens Marcos Minoreli; Gon, Airton dos Santos; Linhares, Rosa Elisa Carvalho

    2014-01-01

    BACKGROUND Herpes simplex virus (HSV) infection is an endemic disease and it is estimated that 6095% of the adult population are infected with symptoms that are usually self-limiting, though they can be serious, extensive and prolonged in immunocompromised individuals, highlighted by the emergence of drug-resistant strains. The study of the wild-type HSV strains based on the cytopathogenic features and its antiviral sensitivity are important in the establishment of an antivirogram for controlling the infection. OBJECTIVE This study sought to isolate and examine the cytopathological characteristics of circulating strains of the Herpes simplex virus, from clinical specimens and their sensitivity to commercially available antiherpesvirus drugs, acyclovir, phosphonophormic acid and trifluridine. METHODS Herpes simplex virus isolation, cytopathological features and antiviral sensitivity assays were performed in cell culture by tissue culture infectious dose or plaque forming unit assay. RESULTS From twenty-two clinical specimens, we isolated and adapted nine strains. Overall, the cytopathic effect was detected 24 h post-infection (p.i.) and the presence of syncytia was remarkable 48 h p.i., observed after cell staining. Out of eight isolates, four developed plaques of varying sizes. All the isolates were sensitive to acyclovir, phosphonophormic and trifluridine, with the percentage of virus inhibition (%VI) ranging from 49.7-100%. CONCLUSIONS The methodology for HSV isolation and characterization is a straightforward approach, but the drug sensitivity test, regarded as being of great practical importance, needs to be better understood. PMID:24937819

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

    PubMed

    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.

  7. Reporter cell lines for the detection of herpes simplex viruses.

    PubMed

    Kung, Szu-Hao

    2005-01-01

    Virus culture has played significant roles in basic and clinical virology, with a number of advantages that cannot be attainable by modern molecular techniques. However, virus culture is generally a slower process, as it inevitably takes the period of a full replication cycle of a given virus. A genetically modified cell culture with a virus-inducible marker is described here, using a frequently isolated DNA virus (herpes simplex virus) as a model. The assay system relies on expression of the reporter gene driven by a specific viral promoter that is triggered early in the course of viral infection. The reporter gene employed was green fluorescent protein (GFP) or secreted alkaline phosphatase (SEAP), whose assays offer real-time detection or quantification, respectively. This cell-based assay is simple, rapid, sensitive, specific, and quantitative and serves as a phenotypic method for determination of antiviral susceptibilities.

  8. A Fusogenic Oncolytic Herpes Simplex Virus for Therapy of Advanced Ovarian Cancer

    DTIC Science & Technology

    2007-06-01

    AD_________________ Award Number: DAMD17-03-1-0434 TITLE: A Fusogenic Oncolytic Herpes Simplex ...TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Fusogenic Oncolytic Herpes Simplex Virus for Therapy of Advanced Ovarian Cancer 5b. GRANT NUMBER...oncolytic herpes simplex virus (HSV) can significantly enhance the anti-tumor effect of the virus. Three specific aims have been proposed and they are: 1

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

    PubMed

    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. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells.

    PubMed Central

    Redfield, D C; Richman, D D; Oxman, M N; Kronenberg, L H

    1981-01-01

    Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays. PMID:6265375

  11. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells

    SciTech Connect

    Redfield, D.C.; Richman, D.D.; Oxman, M.N.; Kronenberg, L.H.

    1981-06-01

    Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays.

  12. Autophagy interaction with herpes simplex virus type-1 infection.

    PubMed

    O'Connell, Douglas; Liang, Chengyu

    2016-01-01

    More than 50% of the U.S. population is infected with herpes simplex virus type-I (HSV-1) and global infectious estimates are nearly 90%. HSV-1 is normally seen as a harmless virus but debilitating diseases can arise, including encephalitis and ocular diseases. HSV-1 is unique in that it can undermine host defenses and establish lifelong infection in neurons. Viral reactivation from latency may allow HSV-1 to lay siege to the brain (Herpes encephalitis). Recent advances maintain that HSV-1 proteins act to suppress and/or control the lysosome-dependent degradation pathway of macroautophagy (hereafter autophagy) and consequently, in neurons, may be coupled with the advancement of HSV-1-associated pathogenesis. Furthermore, increasing evidence suggests that HSV-1 infection may constitute a gradual risk factor for neurodegenerative disorders. The relationship between HSV-1 infection and autophagy manipulation combined with neuropathogenesis may be intimately intertwined demanding further investigation.

  13. Autophagy Stimulation Abrogates Herpes simplex Virus-1 Infection

    PubMed Central

    Yakoub, Abraam M.; Shukla, Deepak

    2015-01-01

    Herpes simplex virus-1 (HSV-1) is a double-stranded DNA virus that causes life-long infections. HSV-1 infections may lead to herpetic stromal keratitis that may advance to corneal blindness. HSV-1 infections can also cause fatal conditions, such as herpes encephalitis, or neonatal disease. A major virulence mechanism of HSV-1 is the control of autophagy, an innate immune defense strategy that could otherwise degrade viral particles. Here, to investigate a new mechanism for antiviral therapy, we tested the effect of various autophagy inducers (physiological and pharmacological) on infection. Autophagy stimulation was confirmed to significantly suppress HSV-1 infection in various cell types, without affecting cell viability. This study establishes the importance of autophagy for regulating HSV-1 infection, and provides a proof-of-principle evidence for a novel antiviral mechanism. PMID:25856282

  14. Autophagy interaction with herpes simplex virus type-1 infection

    PubMed Central

    O'Connell, Douglas; Liang, Chengyu

    2016-01-01

    abstract More than 50% of the U.S. population is infected with herpes simplex virus type-I (HSV-1) and global infectious estimates are nearly 90%. HSV-1 is normally seen as a harmless virus but debilitating diseases can arise, including encephalitis and ocular diseases. HSV-1 is unique in that it can undermine host defenses and establish lifelong infection in neurons. Viral reactivation from latency may allow HSV-1 to lay siege to the brain (Herpes encephalitis). Recent advances maintain that HSV-1 proteins act to suppress and/or control the lysosome-dependent degradation pathway of macroautophagy (hereafter autophagy) and consequently, in neurons, may be coupled with the advancement of HSV-1-associated pathogenesis. Furthermore, increasing evidence suggests that HSV-1 infection may constitute a gradual risk factor for neurodegenerative disorders. The relationship between HSV-1 infection and autophagy manipulation combined with neuropathogenesis may be intimately intertwined demanding further investigation. PMID:26934628

  15. Pediatric herpes simplex virus encephalitis: a retrospective multicenter experience.

    PubMed

    Schleede, Lena; Bueter, Wolfgang; Baumgartner-Sigl, Sara; Opladen, Thomas; Weigt-Usinger, Katharina; Stephan, Susanne; Smitka, Martin; Leiz, Steffen; Kaiser, Olaf; Kraus, Verena; van Baalen, Andreas; Skopnik, Heino; Hartmann, Hans; Rostasy, Kevin; Lücke, Thomas; Schara, Ulrike; Häusler, Martin

    2013-03-01

    Knowledge on pediatric herpes simplex virus encephalitis is limited. Here we summarize 6 neonates and 32 children diagnosed by polymerase chain reaction (n = 37) or serological studies (n = 1), respectively. Diagnosis was difficult, as only 15 patients presented neurologic symptoms. Moreover, cerebrospinal fluid glucose, protein, and leukocytes were normal in 6 patients. Subsequently, all but 2 showed neurologic symptoms. Diffusion-weighted neuroimaging was the most sensitive early imaging method. Despite acyclovir treatment, 8 patients experienced early relapses, showing movement abnormalities, impaired vigilance, and seizures. Diffuse white matter changes, found in 3 of 5 relapse patients on neuroimaging, and a negative cerebrospinal fluid herpes simplex virus polymerase chain reaction suggested inflammatory processes. All relapse patients were again treated with acyclovir, and 3 responded to additional corticosteroid treatment. Whereas outcome after relapses was poor, overall outcome was good. No child died; 14 were asymptomatic at discharge, and neuroimaging remained normal in 7 of 30 patients studied.

  16. Evolutionary Origins of Human Herpes Simplex Viruses 1 and 2

    PubMed Central

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

    2014-01-01

    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. PMID:24916030

  17. Burning mouth syndrome due to herpes simplex virus type 1.

    PubMed

    Nagel, Maria A; Choe, Alexander; Traktinskiy, Igor; Gilden, Don

    2015-04-01

    Burning mouth syndrome is characterised by chronic orofacial burning pain. No dental or medical cause has been found. We present a case of burning mouth syndrome of 6 months duration in a healthy 65-year-old woman, which was associated with high copy numbers of herpes simplex virus type 1 (HSV-1) DNA in the saliva. Her pain resolved completely after antiviral treatment with a corresponding absence of salivary HSV-1 DNA 4 weeks and 6 months later.

  18. Guillain-Barre syndrome presenting with sensory disturbance following a herpes virus infection: a case report

    PubMed Central

    2011-01-01

    Introduction We present a case of an unusual clinical manifestation of Guillain-Barre syndrome following a pre-existing herpes virus infection. Although there have been several reports describing the co-existence of herpes virus infection and Guillain-Barre syndrome, we undertook a more in-depth study of the cross-reactivity between herpes viruses and recommend a follow-up study based on serology tests. Case presentation A 39-year-old healthy Caucasian man with Guillain-Barre syndrome presented to our facility initially with sensory disturbance, followed by an atypical descending pattern of clinical progression. On physical examination, our patient showed hot and cold temperature sensory disturbance under the T4 vertebrae level, symmetrically diminished muscle power mainly to his lower limbs, blurred vision, a loss of taste and paresis and diminished reflexes of his lower limbs. Serology test results for common viruses on hospital admission were positive for cytomegalovirus immunoglobulin M, cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin M, herpes simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin M, and varicella zoster virus immunoglobulin G, borderline for Epstein-Barr virus immunoglobulin G and negative for varicella zoster virus immunoglobulin M. At one month after hospital admission his test results were positive for cytomegalovirus immunoglobulin M, cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin G, varicella zoster virus immunoglobulin G, borderline for herpes simplex virus immunoglobulin M and negative for Epstein-Barr virus immunoglobulin M and varicella zoster virus immunoglobulin M. At his six month follow-up, tests were positive for cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin M, herpes simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin G and varicella zoster virus immunoglobulin G and negative for cytomegalovirus

  19. Central nervous system herpes simplex virus infection in afebrile children with seizures.

    PubMed

    Majumdar, Indrajit; Hartley-McAndrew, Michelle E; Weinstock, Arie L

    2012-04-01

    Central nervous system herpes simplex virus infection is suspected in patients presenting with acute-onset seizures and lethargy. The potential neurologic sequelae from untreated herpes infection can prompt empirical acyclovir therapy, even in afebrile subjects. The objectives of this study were to determine the frequency of central nervous system herpes simplex virus infection in children presenting with afebrile seizures and to assess the need for empirical acyclovir therapy. Clinical and laboratory data of children with acute-onset afebrile seizures and children with central nervous system herpes simplex virus infection were compared. Polymerase chain reaction and viral cultures of the cerebrospinal fluid for herpes simplex virus infection were negative in all subjects with afebrile seizures; 32.7% of these subjects were empirically treated with acyclovir. In conclusion, central nervous system herpes simplex virus infection is uncommon in children presenting with afebrile seizures, and acyclovir therapy is rarely necessary in subjects with normal neurologic examination and cerebrospinal fluid analysis.

  20. Reactivation of herpes simplex virus-1 following epilepsy surgery☆

    PubMed Central

    de Almeida, Sérgio Monteiro; Crippa, Ana; Cruz, Cristina; de Paola, Luciano; de Souza, Luciana Paula; Noronha, Lucia; Torres, Luis Fernando Bleggi; Koneski, Julio A.S.; Pessa, Luis Felipe Cavalli; Nogueira, Meri Bordignon; Raboni, Sonia Mara; Silvado, Carlos Eduardo; Vidal, Luine Rosele

    2015-01-01

    Purpose The present study reports a case of encephalitis due to herpes simplex virus-1 (HSV-1), following surgical manipulation of the site of a primary infection. Methods Herpes simplex virus-1 infection was confirmed by CSF PCR and DNA sequencing. Results The patient was an 11-year-old girl who required temporal lobe surgery for epilepsy. She had meningoencephalitis due to HSV at the age of 20 months, and she was treated with acyclovir. Three years later, the patient developed uncontrolled seizures that became more frequent and changed in character at 11 years of age. On the 12th postoperative day, she developed fever and seizures, and she was diagnosed with HSV-1 by positive CSF PCR. She was treated with acyclovir (30 mg/kg/day for 21 days). In this report, we describe the patient and review the relevant literature. 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. PMID:26543809

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

    PubMed Central

    Lecluse, Anne L.Y.; Bruijnzeel-Koomen, Carla A.F.M.

    2010-01-01

    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. PMID:21103195

  2. The interaction between herpes simplex virus and human immunodeficiency virus.

    PubMed

    Celum, Connie L

    2004-04-01

    Many studies indicate that herpes simplex virus (HSV) seropositivity increases the risk of acquiring HIV, with fewer studies also indicating that HSV-2 infection increases the risk of transmitting HIV. In a recent meta-analysis, HSV-2 infection increased the risk of HIV-acquisition two-fold. This increased risk may occur by HSV-2 reactivation disrupting the epithelial barrier and recruiting activated CD4 cells, which are target cells for HIV infection, into the lesion. In vivo and in vitro studies assessing the effect of HSV-2 on HIV transmission demonstrate that HIV-infected CD4 cells are recruited to HSV-infected lesions and that HSV regulatory proteins (ICP0, ICP4, VP16) may upregulate HIV replication, thus increasing the frequency and titre of mucosal HIV shedding. This may occur during both clinical and asymptomatic HSV reactivation. Plausibly, antiherpetic therapy could reduce HIV transmission by decreasing HIV plasma load and/or mucosal HIV shedding, but a proof-of-concept trial is needed to demonstrate this. It also appears that individuals co-infected with HIV and HSV-2 have more frequent HSV recurrences than individuals infected with HSV-2 alone. There is a strong correlation between decreasing CD4 count and increasing rates of HSV reactivation, suggesting that reactivation is linked to immunosuppression. The IHMF recommends that individuals with HIV should be serologically tested for HSV-2. HSV-2 infection should be targeted as a modifiable risk factor for HIV acquisition by testing, counselling and preventing acquisition through behavioural interventions, treatment and antiviral suppression.

  3. The inactivation of herpes simplex virus by some Solanaceae glycoalkaloids.

    PubMed

    Thorne, H V; Clarke, G F; Skuce, R

    1985-12-01

    The infectivity of herpes simplex virus Type I in tissue culture was inhibited by prior incubation with aqueous suspensions of glycoalkaloids in order of activity alpha-chaconine greater than alpha-tomatine greater than alpha-solasonine but not by the corresponding aglycones, solanidine, tomatidine and solasodine. However, inhibition was not only dependent on the presence of a sugar moiety since the glycone alpha-solanine was inactive under the conditions used. The glycones, but not the aglycones, showed cytopathic effects on cellular membranes of Vero cells and erythrocytes; therefore, it is suggested that inactivation of virus results from insertion of the glycones into the viral envelope.

  4. Early Events in Herpes Simplex Virus Infection: a Radioautographic Study

    PubMed Central

    Hummeler, Klaus; Tomassini, Natale; Zajac, Barbara

    1969-01-01

    The early events in herpes simplex virus infection were studied by means of radio-autography. The virus was rapidly taken up by the host cells and uncoated. Viral deoxyribonucleic acid (DNA) reached the nuclear sites of replication in 15 to 30 min after infection. The viral DNA occasionally associated with chromosomes or condensed chromatin but was more frequently found to be randomly distributed. Viral progeny appeared 3 hr after infection. These particles did not show any particular spatial relationship to the parental DNA. The morphological latent period lasted 2.5 hr. Images PMID:4309102

  5. Helicase-primase inhibitors for herpes simplex virus: looking to the future of non-nucleoside inhibitors for treating herpes virus infections.

    PubMed

    Biswas, Subhajit; Sukla, Soumi; Field, Hugh J

    2014-01-01

    Helicase-primase inhibitors (HPIs) are the first new family of potent herpes virus (herpes simplex and varicella-zoster virus) inhibitors to go beyond the preliminary stages of investigation since the emergence of the original nucleoside analog inhibitors. To consider the clinical future of HPIs, this review puts the exciting new findings with two HPIs, amenamevir and pritelivir, into the historical context of antiviral development for the prevention and treatment of herpes simplex virus over the last century and, on this basis, the authors speculate on the potential evolution of these and other non-nucleoside inhibitors in the future.

  6. Herpes viruses and human papilloma virus in nasal polyposis and controls.

    PubMed

    Ioannidis, Dimitrios; Lachanas, Vasileios A; Florou, Zoe; Bizakis, John G; Petinaki, Efthymia; Skoulakis, Charalampos E

    2015-01-01

    Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p=0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%, p=0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  7. Antigenic relatedness of equine herpes virus types 1 and 3.

    PubMed

    Gutekunst, D E; Malmquist, W A; Becvar, C S

    1978-01-01

    Antiserums prepared in specific pathogen free (SPF) ponies were used in direct and indirect immunofluorescence, immunodiffusion, complement fixation and serum neutralization procedures to study the interrelationships of the three types of equine herpes viruses (EHV-1, EHV-2, and EHV-3). Equine cell cultures infected with each type virus fluoresced when stained with homologous conjugated antiserum. In reciprocal tests EHV-1 and EHV-3 cross-fluoresced, but EHV-2 did not cross-fluoresce. Non-infected cell cultures did not fluoresce when stained with the 3 conjugates. EHV-1 and EHV-3 cross-fluoresced in reciprocal indirect fluorescent antibody tests, but no cross-fluorescence was shown with EHV-2. Antigens representing each type of equine herpes virus reacted with their homologous antiserum in the immunodiffusion test. In reciprocal tests, a common line(s) of identity formed with EHV-1 and EHV-3; however, the precipitin line(s) was not common with EHV-2. Antigen prepared from noninfected embryonic mule skin (EMS) cell cultures did not react with any of the antiserums. Specific complement-fixing antibodies were present in antiserums when tested against their homologous antigens. In reciprocal complement fixation tests EHV-1 and EHV-3 crossreacted, but no cross-reactivity was shown with EHV-2. Significant levels of neutralizing antibody were in an antiserum when tested against homologous virus, whereas cross-neutralization was not detectable in reciprocal tests. These studies indicate that each type of equine herpes virus contains specific antigenic components, and EHV-1 and EHV-3 share a common antigen(s) that is not shared with EHV-2.

  8. Incidence of Alpha-Herpes virus induced ocular disease in Suriname.

    PubMed

    Adhin, Malti R; Grunberg, Meritha G; Labadie-Bracho, Mergiory; Pawiroredjo, Jerrel

    2012-12-01

    Herpes simplex virus (HSV) infection of the corneal stroma is the most prominent cause of scar formation impairing visual acuity and HSV keratitis is the leading cause of corneal opacity throughout the world. Suriname lacked test systems for microbial causes of ocular disease, therefore a polymerase chain reaction-based Herpes virus assay was introduced, enabling prompt recognition, and timely treatment, preventing progressive eye damage. The incidence and epidemiology of Herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), and varicella zoster virus (VZV) in ocular disease in Suriname was assessed. In a cross-sectional prospective study, ocular swabs were collected from 91 patients with a presumptive α-Herpes virus ocular infection attending the Academic Hospital between November 2008 and August 2010 and were tested by a PCR-based α-Herpes virus assay. Alpha-Herpes virus ophthalmic infections were caused predominantly by HSV-1 with a prevalence of 31%. The prevalences of VZV, HSV-2, and a mixed HSV-1/HSV-2 infection were 4%, 3%, and 2%, respectively. The first reported annual incidence of herpetic induced ocular disease in Suriname was estimated at 11.4 per 100,000 person-years (95% CI, 4.8-18.1). No clear age, ethnic or gender dependent difference in incidence was observed. The information obtained on α-Herpes virus positive ocular infections and the distribution of subtypes provided the first insight in the South American situation of α-Herpes virus induced ocular disease.

  9. Isolation of a new herpes virus from human CD4 sup + T cells

    SciTech Connect

    Frenkel, N.; Schirmer, E.C.; Wyatt, L.S.; Katsafanas, G.; Roffman, E.; Danovich, R.M. ); June, C.H. )

    1990-01-01

    A new human herpes virus has been isolated from CD4{sup +} T cells purified from peripheral blood mononuclear cells of a healthy individual (RK), following incubation of the cells under conditions promoting T-cell activation. The virus could not be recovered from nonactivated cells. Cultures of lymphocytes infected with the RK virus exhibited a cytopathic effect, and electron microscopic analyses revealed a characteristic herpes virus structure. RK virus DNA did not hybridize with large probes derived from herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, and human cytomegalovirus. The genetic relatedness of the RK virus to the recently identified T-lymphotropic human herpes virus 6 (HHV-6) was investigated by restriction enzyme analyses using 21 different enzymes and by blot hydridization analyses using 11 probes derived from two strains of HHV-6 (Z29 and U1102). Whereas the two HHV-6 strains exhibited only limited restriction enzyme polymorphism, cleavage of the RK virus DNA yielded distinct patterns. Of the 11 HHV-6 DNA probes tested, only 6 cross-hybridized with DNA fragments derived from the RK virus. Taken together, the maximal homology amounted to 31 kilobases of the 75 kilobases tested. The authors conclude that the RK virus is distinct from previously characterized human herpesviruses. The authors propose to designate it as the prototype of a new herpes virus, the seventh human herpes virus identified to date.

  10. Thin-layer immunoassay for determination of antibodies to herpes simplex virus.

    PubMed Central

    Jeansson, S; Elwing, H; Nilsson, L A

    1979-01-01

    Thin-layer immunoassay (TIA) is a simple serological technique suitable for analysis of large numbers of samples. In this study, TIA was evaluated for determination of antibodies to herpes simplex virus. Herpes simplex virus antigen used in TIA was purified from material released from virus-infected cells. The results obtained by TIA were compared with those obtained by neutralization and complement fixation tests. TIA was found to be as sensitive as the neutralization test for demonstration of herpes simplex virus antibodies. No false-negative or -positive reactions were observed. In primary herpes simplex virus-1 infections, an antibody response was demonstrated by TIA, whereas antibodies could not be demonstrated in patients with primary herpes simplex virus-2 infections. Images PMID:222798

  11. The effect of lithium chloride on the replication of herpes simplex virus.

    PubMed

    Skinner, G R; Hartley, C; Buchan, A; Harper, L; Gallimore, P

    1980-01-01

    Lithium chloride inhibited the replication of type 1 and type 2 Herpes simplex virus at concentrations which permitted host cell replication. Virus polypeptide and antigen synthesis were unaffected while viral DNA synthesis was inhibited. The replication of two other DNA viruses, pseudorabies and vaccinia virus, was inhibited but there was no inhibition of two RNA viruses, namely, EMC and influenze virus.

  12. Oncotarget Strategies For Herpes Simplex Virus-1.

    PubMed

    Zhang, Lumin; Tatsuya, Tsurumi; Nishiyama, Yukihiro

    2016-01-01

    The high level of manipulability of viral genome has set up HSV-1 to be an ideal viral vector for oncolytic virotherapy. In the past two decades, several oncolytic HSV-1 viruses have been successfully developed and assessed in animal studies. Accumulated evidences show that oncolytic HSV- 1 can efficiently infect many tumor cells and augment anti-tumor effect by induction of systemic innate and adaptive immune responses. Inspiring results have been accomplished in several phase I clinical trials for glioma, head and neck squeous cells carcinoma and Melanoma using oncolytic HSV- 1 viruses. More recently, oncovey, one of oncolytic HSV-1 viruses has been approved by FDA for the comprehensive evolution of its anti-tumor effects in phase III clinical trials. These promising studies encourage more efforts to be devoted to craft the new generation of oncolytic HSV-1. Herein, we will review and summarize the basic strategies to construct oncolytic HSV-1 viruses and their applications in cancer therapy.

  13. RNA interference inhibits herpes simplex virus type 1 isolated from saliva samples and mucocutaneous lesions.

    PubMed

    Silva, Amanda Perse da; Lopes, Juliana Freitas; Paula, Vanessa Salete de

    2014-01-01

    The aim of this study was to evaluate the use of RNA interference to inhibit herpes simplex virus type-1 replication in vitro. For herpes simplex virus type-1 gene silencing, three different small interfering RNAs (siRNAs) targeting the herpes simplex virus type-1 UL39 gene (sequence si-UL 39-1, si-UL 39-2, and si-UL 39-3) were used, which encode the large subunit of ribonucleotide reductase, an essential enzyme for DNA synthesis. Herpes simplex virus type-1 was isolated from saliva samples and mucocutaneous lesions from infected patients. All mucocutaneous lesions' samples were positive for herpes simplex virus type-1 by real-time PCR and by virus isolation; all herpes simplex virus type-1 from saliva samples were positive by real-time PCR and 50% were positive by virus isolation. The levels of herpes simplex virus type-1 DNA remaining after siRNA treatment were assessed by real-time PCR, whose results demonstrated that the effect of siRNAs on gene expression depends on siRNA concentration. The three siRNA sequences used were able to inhibit viral replication, assessed by real-time PCR and plaque assays and among them, the sequence si-UL 39-1 was the most effective. This sequence inhibited 99% of herpes simplex virus type-1 replication. The results demonstrate that silencing herpes simplex virus type-1 UL39 expression by siRNAs effectively inhibits herpes simplex virus type-1 replication, suggesting that siRNA based antiviral strategy may be a potential therapeutic alternative.

  14. Novel agents and strategies to treat herpes simplex virus infections.

    PubMed

    Kleymann, Gerald

    2003-02-01

    The quiet pandemic of herpes simplex virus (HSV) infection has plagued humanity since ancient times, causing mucocutaneous infection, such as herpes labialis and herpes genitalis. Disease symptoms often interfere with everyday activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immunocompromised patient population. After primary or initial infection the virus persists for life in a latent form in neurons of the host, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently, no cure is available. In the mid-1950s the first antiviral, idoxuridine, was developed for topical treatment of herpes disease and, in 1978, vidarabine was licensed for systemic use to treat HSV encephalitis. Acyclovir (Zovirax), a potent, specific and tolerable nucleosidic inhibitor of the herpes DNA polymerase, was a milestone in the development of antiviral drugs in the late 1970s. In the mid-1990s, when acyclovir became a generic drug, valacyclovir (Valtrex) and famciclovir (Famvir), prodrugs of the gold standard and penciclovir (Denavir), Vectavir), a close analogue, were launched. Though numerous approaches and strategies were tested and considerable effort was expended in the search of the next generation of an antiherpetic therapy, it proved difficult to outperform acyclovir. Notable in this regard was the award of a Nobel Prize in 1988 for the elucidation of mechanistic principles which resulted in the development of new drugs such as acyclovir. Vaccines, interleukins, interferons, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or nonspecific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir, penciclovir and famciclovir as the first choice of treatment. Recently though, new inhibitors of the HSV helicase-primase with potent in vitro

  15. Herpes Virus Fusion and Entry: A Story with Many Characters

    PubMed Central

    Eisenberg, Roselyn J.; Atanasiu, Doina; Cairns, Tina M.; Gallagher, John R.; Krummenacher, Claude; Cohen, Gary H.

    2012-01-01

    Herpesviridae comprise a large family of enveloped DNA viruses all of whom employ orthologs of the same three glycoproteins, gB, gH and gL. Additionally, herpesviruses often employ accessory proteins to bind receptors and/or bind the heterodimer gH/gL or even to determine cell tropism. Sorting out how these proteins function has been resolved to a large extent by structural biology coupled with supporting biochemical and biologic evidence. Together with the G protein of vesicular stomatitis virus, gB is a charter member of the Class III fusion proteins. Unlike VSV G, gB only functions when partnered with gH/gL. However, gH/gL does not resemble any known viral fusion protein and there is evidence that its function is to upregulate the fusogenic activity of gB. In the case of herpes simplex virus, gH/gL itself is upregulated into an active state by the conformational change that occurs when gD, the receptor binding protein, binds one of its receptors. In this review we focus primarily on prototypes of the three subfamilies of herpesviruses. We will present our model for how herpes simplex virus (HSV) regulates fusion in series of highly regulated steps. Our model highlights what is known and also provides a framework to address mechanistic questions about fusion by HSV and herpesviruses in general. PMID:22754650

  16. [The differential diagnosis of amyotrophic lateral sclerosis and subacute herpes virus myelitis].

    PubMed

    Levitsky, G N; Zavalishin, E E; Chub, R V; Morozova, E A; Serkov, S V

    2016-01-01

    Differential diagnosis of incurable and potentially curable neurological diseases is an urgent problem of modern neurology. The authors present a case report of subacute herpes virus myelitis, a rare complication of herpes infection by Varicella-Zoster virus. The differential diagnosis with amyotrophic lateral sclerosis is described.

  17. Association between Psychopathic Disorder and Serum Antibody to Herpes Simplex Virus (Type 1)

    PubMed Central

    Cleobury, J. F.; Skinner, G. R. B.; Thouless, M. E.; Wildy, P.

    1971-01-01

    The sera of a small of patients has been examined for herpes simplex virus antibody. Three clinically-defined groups of patients were compared: (a) aggressive psychopaths, (b) psychiatric controls, and (c) general hospital patients. The first group had an unusually high average kinetic neutralization constant against type 1 herpes simplex virus. PMID:5543996

  18. Association between psychopathic disorder and serum antibody to herpes simplex virus (type 1).

    PubMed

    Cleobury, J F; Skinner, G R; Thouless, M E; Wildy, P

    1971-02-20

    The sera of a small of patients has been examined for herpes simplex virus antibody. Three clinically-defined groups of patients were compared: (a) aggressive psychopaths, (b) psychiatric controls, and (c) general hospital patients. The first group had an unusually high average kinetic neutralization constant against type 1 herpes simplex virus.

  19. Molecular mimicry in virus infection: crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments.

    PubMed Central

    Fujinami, R S; Oldstone, M B; Wroblewska, Z; Frankel, M E; Koprowski, H

    1983-01-01

    Using monoclonal antibodies, we demonstrate that the phosphoprotein of measles virus and a protein of herpes simplex virus type 1 crossreact with an intermediate filament protein of human cells. This intermediate filament protein, probably vimentin, has a molecular weight of 52,000, whereas the molecular weights of the measles viral phosphoprotein and the herpes virus protein are 70,000 and 146,000, respectively. Crossreactivity was shown by immunofluorescent staining of infected and uninfected cells and by immunoblotting. The monoclonal antibody against measles virus phosphoprotein did not react with herpes simplex virus protein and vice versa, indicating that these monoclonal antibodies recognize different antigenic determinants on the intermediate filament molecule. The significance of these results in explaining the appearance of autoantibodies during virus infections in humans is discussed. Images PMID:6300911

  20. Preparation and efficacy of an inactivated subunit vaccine (NFUIBHK) against type 2 Herpes simplex virus infection.

    PubMed

    Skinner, G R; Williams, D R; Buchan, A; Whitney, J; Harding, M; Bodfish, K

    1978-11-17

    A vaccine against Herpes simplex virus infection was prepared by Nonidet NP 40 and formalin treatment of a type 1, infected-cell extract; virus particles were removed by ultracentrifugation over sucrose. These procedures were not detrimental to the antigenic quality of the vaccine preparation. The vaccine afforded significant protection to experimental type 2 genital herpes virus infection in mice, as adjudged by clinical observations, cytopathological change, and virus yields.

  1. Mother-to-Child Transmission of Herpes Simplex Virus.

    PubMed

    James, Scott H; Sheffield, Jeanne S; Kimberlin, David W

    2014-09-01

    Infections with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), both alpha herpesviruses, are highly prevalent worldwide. Both HSV types commonly cause genital infection, which, when acquired or reactivated during pregnancy, carries with it the risk of transmission to the fetus or neonate. Women who acquire primary or first-episode genital herpes during pregnancy are at greater risk for transmitting the infection than are women with recurrent genital herpes. Because viral infection and reactivation are frequently asymptomatic, many affected women are unaware of their infection and risk of transmission to their infants. Neonatal HSV infection can have devastating long-term consequences, especially when the central nervous system (CNS) is involved. Treatment of affected neonates with intravenous acyclovir has improved outcomes but there is room for further improvement, especially in regard to CNS disease. Working with pregnant women to prevent mother-to-child transmission of HSV is an important component in reducing the overall disease burden of neonatal HSV infections.

  2. Anti-herpes virus activity of Dunbaria bella Prain.

    PubMed

    Akanitapichat, Pannarat; Wangmaneerat, Aree; Wilairat, Prapon; Bastow, Kenneth F

    2006-04-21

    The herpes inhibitory effect of Dunbaria bella Prain (Fabaceae), a Thai medicinal plant traditionally used to treat viral infections was investigated. Using a bioassay-guided fractionation procedure, tertiary fractionation of a dichloromethane-methanol plant extract afforded a partially purified fraction (Fr.372) equally active against replication of herpes simplex virus (HSV) types 1 and 2. The 50% inhibitory concentration determined by a viral yield-inhibition assay was 1.21-1.25 microg/ml and the antiviral selectivity was about 17-fold. Treatment of HSV with high concentrations of Fr.372 followed by removal before infection had little effect on subsequent viral yield indicating the active principle(s) were not inactivating the virus. Concentrations greater than 0.5 microg/ml significantly inhibited viral release more than cell-associated virus suggesting that one or more active ingredients may inhibit viral release. Furthermore, the antiviral activity was dependent on multiplicity of infection and the type of host cell. Preliminary chemical analysis showed that Fr.372 contained neither phenolic compounds nor alkaloids.

  3. Rapid Detection of Herpes Viruses for Clinical Applications

    NASA Technical Reports Server (NTRS)

    Pierson, Duane; Mehta, Satish

    2013-01-01

    There are eight herpes viruses that infect humans, causing a wide range of diseases resulting in considerable morbidity and associated costs. Varicella zoster virus (VZV) is a human herpes virus that causes chickenpox in children and shingles in adults. Approximately 1,000,000 new cases of shingles occur each year; post-herpetic neuralgia (PHN) follows shingles in 100,000 to 200,000 people annually. PHN is characterized by debilitating, nearly unbearable pain for weeks, months, and even years. The onset of shingles is characterized by pain, followed by the zoster rash, leading to blisters and severe pain. The problem is that in the early stages, shingles can be difficult to diagnose; chickenpox in adults can be equally difficult to diagnose. As a result, both diseases can be misdiagnosed (false positive/negative). A molecular assay has been adapted for use in diagnosing VZV diseases. The polymerase chain reaction (PCR) assay is a non-invasive, rapid, sensitive, and highly specific method for VZV DNA detection. It provides unequivocal results and can effectively end misdiagnoses. This is an approximately two-hour assay that allows unequivocal diagnosis and rapid antiviral drug intervention. It has been demonstrated that rapid intervention can prevent full development of the disease, resulting in reduced likelihood of PHN. The technology was extended to shingles patients and demonstrated that VZV is shed in saliva and blood of all shingles patients. The amount of VZV in saliva parallels the medical outcome.

  4. Animal models of herpes simplex virus immunity and pathogenesis.

    PubMed

    Kollias, Christina M; Huneke, Richard B; Wigdahl, Brian; Jennings, Stephen R

    2015-02-01

    Herpes simplex viruses are ubiquitous human pathogens represented by two distinct serotypes: herpes simplex virus (HSV) type 1 (HSV-1); and HSV type 2 (HSV-2). In the general population, adult seropositivity rates approach 90% for HSV-1 and 20-25% for HSV-2. These viruses cause significant morbidity, primarily as mucosal membrane lesions in the form of facial cold sores and genital ulcers, with much less common but more severe manifestations causing death from encephalitis. HSV infections in humans are difficult to study in many cases because many primary infections are asymptomatic. Moreover, the neurotropic properties of HSV make it much more difficult to study the immune mechanisms controlling reactivation of latent infection within the corresponding sensory ganglia and crossover into the central nervous system of infected humans. This is because samples from the nervous system can only be routinely obtained at the time of autopsy. Thus, animal models have been developed whose use has led to a better understanding of multiple aspects of HSV biology, molecular biology, pathogenesis, disease, and immunity. The course of HSV infection in a spectrum of animal models depends on important experimental parameters including animal species, age, and genotype; route of infection; and viral serotype, strain, and dose. This review summarizes the animal models most commonly used to study HSV pathogenesis and its establishment, maintenance, and reactivation from latency. It focuses particularly on the immune response to HSV during acute primary infection and the initial invasion of the ganglion with comparisons to the events governing maintenance of viral latency.

  5. Celiac Crisis Associated with Herpes Simplex Virus Esophagitis

    PubMed Central

    Linz, Christopher M.; Tsay, Julie L.; Jin, Ming; El-Dika, Samer S.

    2016-01-01

    Celiac crisis is a rare presentation of celiac disease that is characterized by life-threatening electrolyte abnormalities, vitamin and mineral deficiencies, and diarrhea. Triggers for celiac crisis include major surgeries, pancreatitis, and infections of cytomegalovirus, and salmonella. A 24-year-old woman presented with celiac crisis associated with severe herpes simplex virus (HSV) esophagitis. This case demonstrates that nutritional deficiencies seen in celiac disease can result in a relative immunodeficiency, which may lead to other infectious complications. Additionally, early recognition of celiac crisis is imperative as the metabolic derangements may be life-threatening, and therapy with gluten restriction and nutritional repletion is effective. PMID:27921058

  6. Herpes Simplex Virus Oncolytic Therapy for Pediatric Malignancies

    PubMed Central

    Friedman, Gregory K; Pressey, Joseph G; Reddy, Alyssa T; Markert, James M; Gillespie, G Yancey

    2009-01-01

    Despite improving survival rates for children with cancer, a subset of patients exist with disease resistant to traditional therapies such as surgery, chemotherapy, and radiation. These patients require newer, targeted treatments used alone or in combination with more traditional approaches. Oncolytic herpes simplex virus (HSV) is one of these newer therapies that offer promise for several difficult to treat pediatric malignancies. The potential benefit of HSV therapy in pediatric solid tumors including brain tumors, neuroblastomas, and sarcomas is reviewed along with the many challenges that need to be addressed prior to moving oncolytic HSV therapy from the laboratory to the beside in the pediatric population. PMID:19367259

  7. Luxury perfusion phenomenon in acute herpes simplex virus encephalitis.

    PubMed

    Tanaka, M; Uesugi, M; Igeta, Y; Kondo, S; Sun, X; Hirai, S

    1995-02-01

    In a patient with acute herpes simplex virus (HSV) encephalitis, positron emission tomography (PET) demonstrated increased cerebral blood flow in the affected temporal lobe accompanied by reduction in the cerebral oxygen extraction fraction and the cerebral metabolic rate of oxygen, i.e., luxury perfusion. Follow-up PET studies showed reduction in cerebral perfusion until it was more closely coupled with oxygen metabolism after the resolution of the acute inflammation. These findings support previous single photon emission computed tomographic data and provide a pathophysiological background for the occurrence of hyperperfusion in HSV encephalitis. This is an interesting example of the luxury perfusion phenomenon occurring in a disease other than cerebral ischemia.

  8. Orbital apex syndrome secondary to herpes zoster virus infection

    PubMed Central

    Merino-Iglesias, Alexia; Montero, Javier Antonio; Calabuig-Goena, Maria; Giraldo-Agudelo, Luisa Fernanda

    2014-01-01

    A male patient with herpes zoster ophthalmicus (HZO) presented with left exophthalmos, external and internal ophthalmoplegia and decreased visual acuity. A CT scan revealed myositis without significant compression of the optic nerve. Intravenous acyclovir and oral steroids were started with improvement of the symptoms and eventual complete recovery.Orbital apex syndrome is a rare complication of HZO. Multiple pathogenic mechanisms are involved, including a direct cytopathic effect of the virus as in the present case. Early diagnosis and therapy may lead to complete recovery of visual function. PMID:24614776

  9. Herpes simplex virus oncolytic therapy for pediatric malignancies.

    PubMed

    Friedman, Gregory K; Pressey, Joseph G; Reddy, Alyssa T; Markert, James M; Gillespie, G Yancey

    2009-07-01

    Despite improving survival rates for children with cancer, a subset of patients exist with disease resistant to traditional therapies such as surgery, chemotherapy, and radiation. These patients require newer, targeted treatments used alone or in combination with more traditional approaches. Oncolytic herpes simplex virus (HSV) is one of these newer therapies that offer promise for several difficult to treat pediatric malignancies. The potential benefit of HSV therapy in pediatric solid tumors including brain tumors, neuroblastomas, and sarcomas is reviewed along with the many challenges that need to be addressed prior to moving oncolytic HSV therapy from the laboratory to the beside in the pediatric population.

  10. Reactivation of herpes simplex virus keratitis after initiating bimatoprost treatment for glaucoma.

    PubMed

    Kroll, Debra M; Schuman, Joel S

    2002-03-01

    To report a case of herpes simplex virus reactivation after starting bimatoprost treatment for glaucoma. Interventional case report. A 66-year-old woman had a herpes simplex keratouveitis reactivation that occurred within 1 month after starting bimatoprost. The herpes simplex had been inactive for more than 10 years. Bimatoprost and prednisolone acetate 0.12% were discontinued; oral acyclovir, ofloxacin, and betaxolol 0.25% were initiated. Two weeks later, prednisolone acetate 1% was added. The reactivation resolved, and 1 month later, the best corrected visual acuity improved to 20/40. Caution should be used in prescribing bimatoprost for patients with a history of herpes simplex virus keratitis.

  11. Expression of Herpes Simplex Virus 1 Glycoprotein B by a Recombinant Vaccinia Virus and Protection of Mice against Lethal Herpes Simplex Virus 1 Infection

    NASA Astrophysics Data System (ADS)

    Cantin, Edouard M.; Eberle, Richard; Baldick, Joseph L.; Moss, Bernard; Willey, Dru E.; Notkins, Abner L.; Openshaw, Harry

    1987-08-01

    The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modified at the 5' end by in vitro oligonucleotide-directed mutagenesis. The modified gB gene was inserted into the vaccinia virus genome and expressed under the control of a vaccinia virus promoter. The mature gB glycoprotein produced by the vaccinia virus recombinant was glycosylated, was expressed at the cell surface, and was indistinguishable from authentic HSV-1 gB in terms of electrophoretic mobility. Mice immunized intradermally with the recombinant vaccinia virus produced gB-specific neutralizing antibodies and were resistant to a lethal HSV-1 challenge.

  12. Evidence of Muller's ratchet in herpes simplex virus type 1.

    PubMed

    Jaramillo, Nacarí; Domingo, Esteban; Muñoz-Egea, María Carmen; Tabarés, Enrique; Gadea, Ignacio

    2013-02-01

    Population bottlenecks can have major effects in the evolution of RNA viruses, but their possible influence in the evolution of DNA viruses is largely unknown. Genetic and biological variation of herpes simplex virus type 1 (HSV-1) has been studied by subjecting 23 biological clones of the virus to 10 plaque-to-plaque transfers. In contrast to large population passages, plaque transfers led to a decrease in replicative capacity of HSV-1. Two out of a total of 23 clones did not survive to the last transfer in 143 TK(-) cells. DNA from three genomic regions (DNA polymerase, glycoprotein gD and thymidine kinase) from the initial and passaged clones was sequenced. Nucleotide substitutions were detected in the TK and gD genes, but not in the DNA polymerase gene. Assuming a uniform distribution of mutations along the genome, the average rate of fixation of mutations was about five mutations per viral genome and plaque transfer. This value is comparable to the range of values calculated for RNA viruses. Four plaque-transferred populations lost neurovirulence for mice, as compared with the corresponding initial clones. LD(50) values obtained with the populations subjected to serial bottlenecks were 4- to 67-fold higher than for their parental clones. These results equate HSV-1 with RNA viruses regarding fitness decrease as a result of plaque-to-plaque transfers, and show that population bottlenecks can modify the pathogenic potential of HSV-1. Implications for the evolution of complex DNA viruses are discussed.

  13. Possible peptide chain termination mutants in thymide kinase gene of a mammalian virus, herpes simplex virus.

    PubMed

    Summers, W P; Wagner, M; Summers, W C

    1975-10-01

    Mutations in the viral gene coding for the thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) induced by herpes simplex virus have been obtained by selection of virus resistant to bromodeoxyuridine when grown in thymidine-kinase-deficient LMTK- mouse cells. Proteins labeled after infection of Vero (monkey) cells with herpes simplex virus were analyzed by gel electrophoresis and one protein of about 40,000 daltons was consistently altered in a number of thymidine-kinase-deficient mutants. Many viral mutants lacked this peptide and one class of these mutants induced the synthesis of new shorter peptides. Revertant virus could be selected which simultaneously regained the ability to induce thymidine kinase activity, regained the intact thymidine kinase peptide, and lost the ability to synthesize the shorter peptide fragment. These mutants comprise a class of animal virus mutants which have the properties expected of peptide chain termination mutants.

  14. Possible peptide chain termination mutants in thymide kinase gene of a mammalian virus, herpes simplex virus.

    PubMed Central

    Summers, W P; Wagner, M; Summers, W C

    1975-01-01

    Mutations in the viral gene coding for the thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) induced by herpes simplex virus have been obtained by selection of virus resistant to bromodeoxyuridine when grown in thymidine-kinase-deficient LMTK- mouse cells. Proteins labeled after infection of Vero (monkey) cells with herpes simplex virus were analyzed by gel electrophoresis and one protein of about 40,000 daltons was consistently altered in a number of thymidine-kinase-deficient mutants. Many viral mutants lacked this peptide and one class of these mutants induced the synthesis of new shorter peptides. Revertant virus could be selected which simultaneously regained the ability to induce thymidine kinase activity, regained the intact thymidine kinase peptide, and lost the ability to synthesize the shorter peptide fragment. These mutants comprise a class of animal virus mutants which have the properties expected of peptide chain termination mutants. Images PMID:172894

  15. CSF herpes virus and autoantibody profiles in the evaluation of encephalitis.

    PubMed

    Linnoila, Jenny J; Binnicker, Matthew J; Majed, Masoud; Klein, Christopher J; McKeon, Andrew

    2016-08-01

    To report the frequency of coexisting herpes viruses (herpes simplex virus 1 [HSV-1] or HSV-2, varicella zoster virus, Epstein-Barr virus [EBV], cytomegalovirus, or human herpes virus 6 [HHV-6]) and autoantibodies in patients with encephalitis (herpes or autoimmune) in clinical laboratory service. Three groups were evaluated for herpes viruses and antibodies: group 1-patients whose CSF was positive for a herpes virus by real-time PCR over a period of 6 months; group 2-patients whose CSF was positive for an autoimmune encephalitis-associated antibody over 5 years (e.g., NMDA receptor [NMDA-R] antibody), and the same number of controls without autoimmune/infectious disease; and group 3-incidental autoimmune parainfectious encephalitis cases encountered over 1 year. In group 1, antibodies were detected in 27 of 100 herpes PCR-positive CSF specimens (CSFs), either unclassified neural or nonneural in all but one patient with NMDA-R antibody detected after EBV infection. Antibodies were also detected in 3 of 7 CSFs submitted for repeat PCR testing (unclassified, 2; AMPA receptor, 1). In group 2, herpes viruses were detected in 1 of 77 controls (HHV-6) and 4 of 77 patients with autoimmune encephalitis (EBV, 2; HHV-6, 2); autoantibodies targeted NMDA-R in 3/4 and GABAB-R in 1/4. In group 3, NMDA-R antibody was detected in 7 patients post-HSV-1 encephalitis. Of the remaining 3 patients, 2 had unclassified neural antibodies detected, and one had GABAB-R autoimmunity. Concomitant neoplasms were discovered in 2 patients each from groups 2 and 3. Autoantibodies and herpes virus DNA frequently coexist in encephalitic CSF. Some patients develop parainfectious autoimmunity following viral CNS infection (usually HSV-1 encephalitis). The significance of detecting herpes nucleic acids in others remains unclear.

  16. Herpes and polyoma family viruses in thyroid cancer

    PubMed Central

    STAMATIOU, DIMITRIS P.; DERDAS, STAVROS P.; ZORAS, ODYSSEAS L.; SPANDIDOS, DEMETRIOS A.

    2016-01-01

    virus families, the herpes and polyoma family viruses, and we discuss their potential role as causative agents in thyroid carcinogenesis. PMID:26998055

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

    PubMed

    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.

  18. Imbalanced oxidative stress causes chlamydial persistence during non-productive human herpes virus co-infection.

    PubMed

    Prusty, Bhupesh K; Böhme, Linda; Bergmann, Birgit; Siegl, Christine; Krause, Eva; Mehlitz, Adrian; Rudel, Thomas

    2012-01-01

    Both human herpes viruses and Chlamydia are highly prevalent in the human population and are detected together in different human disorders. Here, we demonstrate that co-infection with human herpes virus 6 (HHV6) interferes with the developmental cycle of C. trachomatis and induces persistence. Induction of chlamydial persistence by HHV6 is independent of productive virus infection, but requires the interaction and uptake of the virus by the host cell. On the other hand, viral uptake is strongly promoted under co-infection conditions. Host cell glutathione reductase activity was suppressed by HHV6 causing NADPH accumulation, decreased formation of reduced glutathione and increased oxidative stress. Prevention of oxidative stress restored infectivity of Chlamydia after HHV6-induced persistence. We show that co-infection with Herpes simplex virus 1 or human Cytomegalovirus also induces chlamydial persistence by a similar mechanism suggesting that Chlamydia -human herpes virus co-infections are evolutionary shaped interactions with a thus far unrecognized broad significance.

  19. Genital Herpes

    MedlinePlus

    ... Choosing the Right Sport for You Shyness Genital Herpes KidsHealth > For Teens > Genital Herpes Print A A A What's in this article? ... How Is It Prevented? What Is It? Genital herpes is caused by a virus called herpes simplex ( ...

  20. Herpes Simplex

    MedlinePlus

    ... is caused by a herpes simplex virus (HSV). Oral herpes causes cold sores around the mouth or face. Genital herpes affects the genitals, buttocks ... type 2 is the usual cause of genital herpes, but it also can infect the mouth. HSV spreads through direct contact. Some people have ...

  1. Bioactive natural products with anti-herpes simplex virus properties.

    PubMed

    Hassan, Sherif T S; Masarčíková, Radka; Berchová, Kateřina

    2015-10-01

    In this review, we highlight and summarise the most promising extracts, fractions and pure compounds as potential anti-herpes simplex virus (HSV) agents derived from microorganisms, marine organisms, fungi, animals and plants. The role of natural products in the development of anti-HSV drugs will be discussed. Herpes simplex viruses (HSV-1 and -2) are common human pathogens that remain a serious threat to human health. In recent years, a great interest has been devoted to the search for integrated management of HSV infections. Acyclovir and related nucleoside analogues have been licensed for the therapy that target viral DNA polymerase. Although these drugs are currently effective against HSV infections, the intensive use of these drugs has led to the problem of drug-resistant strains. Therefore, the search for new sources to develop new antiherpetic agents has gained major priority to overcome the problem. Natural products as potential, new anti-HSV drugs provide several advantages such as reduced side effects, less resistance, low toxicity and various mechanisms of action. This paper aims to provide an overview of natural products that possess antiviral activity against HSV. © 2015 Royal Pharmaceutical Society.

  2. Necrotizing keratitis caused by acyclovir-resistant herpes simplex virus.

    PubMed

    Toriyama, Koji; Inoue, Tomoyuki; Suzuki, Takashi; Kobayashi, Takeshi; Ohashi, Yuichi

    2014-09-01

    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. Observational case report. 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. 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.

  3. Empiric acyclovir for neonatal herpes simplex virus infection.

    PubMed

    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.

  4. Replication of type 2 herpes simplex virus in human endocervical tissue in organ culture.

    PubMed

    Birch, J; Fink, C G; Skinner, G R; Thomas, G H; Jordan, J A

    1976-08-01

    The replication of type 2 herpes simplex virus in human endocervical tissue in organ culture was investigated. The temporal profile of virus replication was related to the initial virus inoculum; high input inocula induced a rapid increase in virus titre while lower multiplicities induced a more slow-rising increase in virus titre. Our evidence suggested that explants were capable of initiating and supporting virus replication for at least 2 weeks following establishment of the culture. Virus yields were optimal when explants were cultured at 37 degrees and in serum-supplemented medium. Explants also supported the replication of type 1 herpes simplex virus and a "non-human" herpes simplex virus (pseudo-rabies virus). The optimal conditions for replication of type 2 herpes simplex virus in human endocervical explants have been established and will provide a model permitting precise investigation of lytic or other virus-cervical cell interactions and their possible relationship to herpes virus-induced pre-invasive carcinoma of this organ.

  5. Replication of type 2 herpes simplex virus in human endocervical tissue in organ culture.

    PubMed Central

    Birch, J.; Fink, C. G.; Skinner, G. R.; Thomas, G. H.; Jordan, J. A.

    1976-01-01

    The replication of type 2 herpes simplex virus in human endocervical tissue in organ culture was investigated. The temporal profile of virus replication was related to the initial virus inoculum; high input inocula induced a rapid increase in virus titre while lower multiplicities induced a more slow-rising increase in virus titre. Our evidence suggested that explants were capable of initiating and supporting virus replication for at least 2 weeks following establishment of the culture. Virus yields were optimal when explants were cultured at 37 degrees and in serum-supplemented medium. Explants also supported the replication of type 1 herpes simplex virus and a "non-human" herpes simplex virus (pseudo-rabies virus). The optimal conditions for replication of type 2 herpes simplex virus in human endocervical explants have been established and will provide a model permitting precise investigation of lytic or other virus-cervical cell interactions and their possible relationship to herpes virus-induced pre-invasive carcinoma of this organ. Images Fig. 1 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:183806

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

    PubMed

    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.

  7. Corneal latency and transmission of herpes simplex virus-1.

    PubMed

    Farooq, Asim V; Shukla, Deepak

    2011-01-01

    The transmission of herpes simplex virus (HSV)-1 by corneal transplantation has rarely been reported. It is believed that these cases have resulted either from reactivated virus traveling from the trigeminal ganglion to the cornea or from latent HSV-1 in the donor cornea itself. Studies of long-term viral presence in corneal tissue have sought to determine whether there is evidence of true non-neuronal latency, although there are problems in its definition. Recent studies provide new insights into neuronal latency, while similar HSV-1 gene regulation in the cornea may implicate corneal latency in pathophysiology and as a potential risk for transplant recipients. This issue has led to concerns over eye banking, which currently screens for other infectious agents but not HSV-1. Here we review the literature regarding corneal latency and the transmission of HSV-1.

  8. Effect of alkaloids isolated from Amaryllidaceae on herpes simplex virus.

    PubMed

    Renard-Nozaki, J; Kim, T; Imakura, Y; Kihara, M; Kobayashi, S

    1989-01-01

    Studies were carried out on the effects of Amaryllidaceae alkaloids and their derivatives upon herpes simplex virus (type 1), the relationship between their structure and antiviral activity and the mechanism of this activity. All alkaloids used in these experiments were biosynthesized from N-benzylphenethylamine; the apogalanthamine group was synthesized in our laboratory; those which may eventually prove to be antiviral agents had a hexahydroindole ring with two functional hydroxyl groups. Benzazepine compounds were neither cytotoxic nor antiviral, but many structures containing dibenzazocine were toxic at low concentrations. It was established that the antiviral activity of alkaloids is due to the inhibition of multiplication and not to the direct inactivation of extracellular viruses. The mechanism of the antiviral effect could be partly explained as a blocking of viral DNA polymerase activity.

  9. Concurrent reactivation of herpes simplex and varicella zoster viruses confirmed by the loop-mediated isothermal amplification assay.

    PubMed

    Kobayashi, Tsukane; Yagami, Akiko; Suzuki, Kayoko; Yoshikawa, Tetsushi; Matsunaga, Kayoko

    2014-01-01

    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.

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

    PubMed Central

    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

  11. Stromal keratitis in a neonate: Herpes virus a diagnosis to consider.

    PubMed

    Sánchez-Tocino, H; Villanueva, A; Giraldo, L; Anglés, J M; Pérez-Gutiérrez, M E

    2016-02-01

    Neonatal herpes simple virus (HSV) keratitis, relatively uncommon are associated with significant morbidity. The case is presented of a newborn girl who developed herpes simplex virus (HSV) keratoconjunctivitis, despite a vaginal delivery, and the absence of medical history or active clinical maternal HSV infection. Diagnosis relies on a high level of clinical suspicion and the use of diagnostic tests. Neonatal herpes simplex virus (HSV) keratitis, although relatively uncommon, is associated with significant morbidity. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Isolation of a protein kinase induced by herpes simplex virus type 1

    SciTech Connect

    Blue, W.T.; Stobbs, D.G.

    1981-04-01

    Researchers have isolated a new cyclic AMP-independent protein kinase activity induced in HeLa cells by infection with herpes simplex virus type 1. Induction of the enzyme does not occur in cells treated with cycloheximide at the time of infection, or in cells infected with UV-inactivated herpes simplex virus type 1. The amount of enzyme induced in infected cells is dependent upon the multiplicity of infection. An enzyme with identical properties to the appearing in infected HeLa cells is also induced by herpes simplex virus type 1 in BHK cells.

  13. Limb hypoplasia resulting from intrauterine infection with herpes simplex virus: a case report.

    PubMed

    Carola, D; Skibo, M; Cannon, S; Cam, K M; Hyde, P; Aghai, Z H

    2014-11-01

    Intrauterine infection with herpes simplex virus, although very rare, has devastating effects on multiple organ systems in the fetus and can lead to in utero fetal demise. Neonates born following intrauterine herpes simplex virus infection commonly manifest with cutaneous lesions, ocular damage and/or brain abnormalities. We describe the case of a dichorionic, diamniotic twin gestation complicated by intrauterine herpes simplex virus infection. This infection led to the fetal demise of twin A and a very uncommon presentation of limb hypoplasia in twin B.

  14. Immunization against Genital Herpes with a Vaccine Virus That has Defects in Productive and Latent Infection

    NASA Astrophysics Data System (ADS)

    da Costa, Xavier J.; Jones, Cheryl A.; Knipe, David M.

    1999-06-01

    An effective vaccine for genital herpes has been difficult to achieve because of the limited efficacy of subunit vaccines and the safety concerns about live viruses. As an alternative approach, mutant herpes simplex virus strains that are replication-defective can induce protective immunity. To increase the level of safety and to prove that replication was not needed for immunization, we constructed a mutant herpes simplex virus 2 strain containing two deletion mutations, each of which eliminated viral replication. The double-mutant virus induces protective immunity that can reduce acute viral shedding and latent infection in a mouse genital model, but importantly, the double-mutant virus shows a phenotypic defect in latent infection. This herpes vaccine strain, which is immunogenic but has defects in both productive and latent infection, provides a paradigm for the design of vaccines and vaccine vectors for other sexually transmitted diseases, such as AIDS.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  17. Herpes simplex virus reactivation after subtotal hemispherectomy in a pediatric patient.

    PubMed

    Gong, Tracie; Bingaman, William; Danziger-Isakov, Lara; Tuxhorn, Ingrid; Goldfarb, Johanna

    2010-12-01

    We report herpes simplex encephalitis (HSE) in a toddler after a subtotal hemispherectomy for seizures related to HSE 16 months earlier. Herpes simplex virus reactivation in the cerebrospinal fluid shortly after treatment of HSE has been described, but is extremely rare in other situations. HSE reactivation is a potential complication of epilepsy surgery after HSE in children.

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

    PubMed

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

    PubMed

    Blevins, Tamara P; Mitchell, Michelle C; Korom, Maria; Wang, Hong; Yu, Yinyi; Morrison, Lynda A; Belshe, Robert B

    2015-01-01

    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.

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

    PubMed

    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.

  1. Herpes zoster ophthalmicus in patients with human immunodeficiency virus infection.

    PubMed

    Margolis, T P; Milner, M S; Shama, A; Hodge, W; Seiff, S

    1998-03-01

    To investigate the ocular complications of herpes zoster ophthalmicus in patients with human immunodeficiency virus (HIV) infection. This was a retrospective cohort study of 48 HIV-infected patients (48 eyes) treated at San Francisco General Hospital for herpes zoster ophthalmicus from December 1985 through March 1994. All patients were initially treated with either intravenous or oral acyclovir. The median CD4 lymphocyte count at diagnosis was 48 per mm3 (range, 2 to 490 per mm3). Fifteen patients (31%) had mild or no ocular involvement. Seventeen patients (35%) had stromal keratitis, mostly mild, and two (4)% developed chronic infectious pseudodendritic keratitis. Twenty-four study patients (50%) had iritis, but only three (6%) had elevations in intraocular pressure. Two patients (4%) developed postherpetic neuralgia, and two others (4%) had zoster-associated central nervous system disease. Only two patients (4%) developed necrotizing retinitis, both in the form of the progressive outer retinal necrosis syndrome. Excluding the patients with retinitis and central nervous system disease, the rate of sight-threatening complications in our series was lower than expected. Almost one third of study patients had no ocular complications or only mild surface epithelial disease. Although the relatively low incidence of sight-threatening disease in our study population may have been a consequence of aggressive management with acyclovir, chronic infectious pseudodendritic keratitis, retinitis, and central nervous system disease, complications of ophthalmic zoster whose pathogenesis is largely a consequence of active viral replication, were particularly devastating and difficult to manage.

  2. Topical application of polyethylenimine as a candidate for novel prophylactic therapeutics against genital herpes caused by herpes simplex virus.

    PubMed

    Hayashi, Kyoko; Onoue, Hiroki; Sasaki, Kohei; Lee, Jung-Bum; Kumar, Penmetcha K R; Gopinath, Subash C B; Maitani, Yoshie; Kai, Takashi; Hayashi, Toshimitsu

    2014-03-01

    Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) cause genital herpes, which can enhance the acquisition of human immunodeficiency virus. The development of anti-HSV agents with novel mechanisms of action is urgently required in the topical therapy of genital herpes. In this study, the in vitro and in vivo anti-HSV effects of Epomin SP-012(®), a highly cationic polyethylenimine, were evaluated. When the in vitro antiviral effects of SP-012 were assessed, this compound showed potent activity against HSV-1 and HSV-2. It inhibited the attachment of HSV-2 to host cells and cell-to-cell spread of infection in a concentration-dependent manner and exerted a virucidal effect. No SP-012-resistant HSV-2 was found when the virus was successively passaged in the presence of SP-012. In a mouse genital herpes model, topically administered SP-012 inhibited the progression of the disease caused by HSV infection. These data illustrate that SP-012 may be a novel class of HSV inhibitor that would be acceptable for long-term topical application.

  3. Acute retinal necrosis caused by herpes simplex virus type 2 in children: reactivation of an undiagnosed latent neonatal herpes infection.

    PubMed

    Grose, Charles

    2012-09-01

    Herpes simplex virus type 2 (HSV-2) is known to cause acute retinal necrosis (ARN). The availability of HSV-2-specific polymerase chain reaction tests for diagnostic analysis has greatly increased our ability to discriminate ARN caused by HSV-2 from ARN caused by either herpes simplex virus type 1 or varicella zoster virus (VZV). Of great interest, HSV-2 appears to be the most common cause of viral ARN in children and adolescents. Although a few children with ARN are known to have had neonatally acquired herpes infection, most children lack a history of known herpes disease. Thus, the origin of the HSV-2 infection is a mystery. The hypothesis of this review is that HSV-2 ARN in children and adolescents may be the first sign of a previously undiagnosed and asymptomatic neonatal HSV-2 infection, which has reactivated several years later from latency in a cranial nerve and entered the retina. The review brings together 7 previously published ARN cases, plus one new case is added. Thus, this review also expands the spectrum of complications from neonatal HSV-2 infection.

  4. Targeted entry of enveloped viruses: measles and herpes simplex virus I.

    PubMed

    Navaratnarajah, Chanakha K; Miest, Tanner S; Carfi, Andrea; Cattaneo, Roberto

    2012-02-01

    We compare the receptor-based mechanisms that a small RNA virus and a larger DNA virus have evolved to drive the fusion of viral and cellular membranes. Both systems rely on tight control over triggering the concerted refolding of a trimeric fusion protein. While measles virus entry depends on a receptor-binding protein and a fusion protein only, the herpes simplex virus (HSV) is more complex and requires four viral proteins. Nevertheless, in both viruses a receptor-binding protein is required for triggering the membrane fusion process. Moreover, specificity domains can be appended to these receptor-binding proteins to target virus entry to cells expressing a designated receptor. We discuss how principles established with measles and HSV can be applied to targeting other enveloped viruses, and alternatively how retargeted envelopes can be fitted on foreign capsids.

  5. Irreproducibility of neutralization of herpes simplex virus under conditions where antibody is not in excess.

    PubMed

    Shariff, D; Hallworth, J A; Buchan, A; Skinner, G R

    1987-01-01

    Neutralizing activity against herpes simplex virus was significantly reduced if initial virus titers were greater than 10(6) PFU/ml; there was no significant neutralization when initial virus titers approached 10(8) PFU/ml. This was a result of utilization of all available antibody by virus particles and 'free' virus antigen and emphasizes the importance of conducting virus neutralization tests under conditions of antibody excess.

  6. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

    SciTech Connect

    Perna, J.J.; Mannix, M.L.; Rooney, J.F.; Notkins, A.L.; Straus, S.E.

    1987-09-01

    Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation.

  7. Transient lingual papillitis associated with confirmed herpes simplex virus 1 in a patient with kawasaki disease.

    PubMed

    Krakowski, Andrew C; Kim, Silvia S; Burns, Jane C

    2014-01-01

    We present a case of transient lingual papillitis associated with confirmed herpes simplex virus 1 that developed after a child received intravenous immunoglobulin and infliximab for acute Kawasaki disease.

  8. Herpes simplex virus 1 induces de novo phospholipid synthesis

    SciTech Connect

    Sutter, Esther; Oliveira, Anna Paula de; Tobler, Kurt; Schraner, Elisabeth M.; Sonda, Sabrina; Kaech, Andres; Lucas, Miriam S.; Ackermann, Mathias; Wild, Peter

    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.

  9. Prevention and management of neonatal herpes simplex virus infections.

    PubMed

    Allen, Upton D; Robinson, Joan L

    2014-04-01

    Human herpes simplex virus (HSV) infection in neonates can result in devastating outcomes, including mortality and significant morbidity. All infants are potentially at risk for neonatal HSV infection. This position statement reviews epidemiology, transmission and risk factors, with a focus on intrapartum infection. It considers diagnosis and prognosis according to infection category, along with testing modalities and limitations. Recommendations for managing newborns known to have been exposed intrapartum to HSV are based on expert opinion because a randomized trial to compare management options is not feasible. Guidance is provided for the empirical management of infants with suspected clinical sepsis, including those who do not respond to antibacterial therapy. The present statement replaces a 2006 position statement by the Canadian Paediatric Society.

  10. New strategies against drug resistance to herpes simplex virus

    PubMed Central

    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

  11. New-onset refractory status epilepticus mimicking herpes virus encephalitis.

    PubMed

    Puoti, Gianfranco; Elefante, Andrea; Saracino, Dario; Capasso, Antonella; Cotrufo, Roberto; Anello, Clara Belluomo

    2013-01-01

    New-onset refractory status epilepticus (NORSE) is a recently defined clinical entity that describes patients who present with status epilepticus of unclear etiology that is highly refractory to therapy. Magnetic resonance imaging (MRI) of NORSE usually discloses no specific abnormalities except for an occasional mild T2/FLAIR hyperintense signal of the mesial temporal lobe. Here, we report a peculiar case of NORSE in which brain MRI showed massive alteration of both temporal lobes, with features strongly supporting the diagnosis of herpes virus encephalitis, but lacking any laboratory evidence of viral infection in the blood and cerebrospinal fluid. It showed also striking signal alterations in the thalamus, which got worse in the course of the disease. This report emphasizes the possibility that seizure activity alone plays a critical role in both determining the disease and whether it will be self-sustaining.

  12. Basal Autophagy Is Required for Herpes simplex Virus-2 Infection

    PubMed Central

    Yakoub, Abraam M.; Shukla, Deepak

    2015-01-01

    Autophagy is a conserved catabolic process of the cell, which plays an important role in regulating plethora of infections. The role of autophagy in Herpes simplex virus-2 (HSV-2) infection is unknown. Here, we found that HSV-2 does not allow induction of an autophagic response to infection, but maintains basal autophagy levels mostly unchanged during productive infection. Thus, we investigated the importance of basal autophagy for HSV-2 infection, using pharmacological autophagy suppression or cells genetically deficient in an autophagy-essential gene (ATG5). Interference with basal autophagy flux in cells significantly reduced viral replication and diminished the infection. These results indicate that basal autophagy plays an indispensable role required for a productive infection. Importantly, this study draws a sharp distinction between induced and basal autophagy, where the former acts as a viral clearance mechanism abrogating infection, while the latter supports infection. PMID:26248741

  13. Lytic Promoters Express Protein during Herpes Simplex Virus Latency

    PubMed Central

    Russell, Tiffany A.; Tscharke, David C.

    2016-01-01

    Herpes simplex virus (HSV) has provided the prototype for viral latency with previously well-defined acute or lytic and latent phases. More recently, the deep quiescence of HSV latency has been questioned with evidence that lytic genes can be transcribed in this state. However, to date the only evidence that these transcripts might be translated has come from immunological studies that show activated T cells persist in the nervous system during latency. Here we use a highly sensitive Cre-marking model to show that lytic and latent phases are less clearly defined in two significant ways. First, around half of the HSV spread leading to latently infected sites occurred beyond the initial acute infection and second, we show direct evidence that lytic promoters can drive protein expression during latency. PMID:27348812

  14. Herpesviridae infections in newborns: varicella zoster virus, herpes simplex virus, and cytomegalovirus.

    PubMed

    Enright, Andrea M; Prober, Charles G

    2004-08-01

    Varicella zoster virus (VZV), herpes simplex virus (HSV) and cytomegalovirus (CMV) are all members of the Herpesviridae family.Humans are the only source of infection for these double stranded DNA viruses. Infants may acquire these infections in utero, peripartum, or postnatally, resulting in a variety of clinical syndromes, ranging from asymptomatic infection to severe infection,with high mortality rates and significant long-term morbidity. This article presents the epidemiology, clinical characteristics, treatment,and prevention strategies for VZV, HSV, and CMV infections in infants.

  15. Molecular Characterization of Prostate Cancer Cell Oncolysis by Herpes Simplex Virus ICP0 Mutants

    DTIC Science & Technology

    2006-04-01

    W81XWH-04-1-0859 TITLE: Molecular Characterization of Prostate Cancer Cell Oncolysis byHerpes Simplex Virus ICP0 Mutants PRINCIPAL...2. REPORT TYPE Final 3. DATES COVERED (From - To) 15 Sep 04 – 14 Mar 06 5a. CONTRACT NUMBER Molecular Characterization of Prostate Cancer Cell...Herpes simplex virus type 1 ICP0 mutants in prostate cancer cells given the relationship between ICP0 and two tumor suppressors, RNase L and PML

  16. Herpes zoster could be an early manifestation of undiagnosed human immunodeficiency virus infection.

    PubMed

    Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu; Chen, Wen-Chi

    2016-05-01

    No formal epidemiological research based on systematic analysis has focused on the relationship between herpes zoster and immunodeficiency virus (HIV) infection in Taiwan. Our aim was to explore whether herpes zoster is an early manifestation of undiagnosed human HIV infection in Taiwan. This was a retrospective cohort study using the database of the Taiwan National Health Insurance Program. A total of 35,892 individuals aged ≤ 84 years with newly diagnosed herpes zoster from 1998 to 2010 were assigned to the herpes zoster group, whereas 143,568 sex-matched and age-matched, randomly selected individuals without herpes zoster served as the non-herpes zoster group. The incidence of HIV diagnosis at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence interval (CI) for risk of HIV diagnosis associated with herpes zoster and other comorbidities including drug dependence and venereal diseases. The overall incidence of HIV diagnosis was 4.19-fold greater in the herpes zoster group than that in the non-herpes zoster group (3.33 per 10,000 person-years vs. 0.80 per 10,000 person-years, 95% CI 4.04-4.35). The multivariable Cox proportional hazards regression analysis revealed that the adjusted hazard ratio of HIV diagnosis was 4.37 (95% CI 3.10-6.15) for individuals with herpes zoster and without comorbidities, as compared with individuals without herpes zoster and without comorbidities. Herpes zoster is associated with HIV diagnosis. Patients who have risk behaviors of HIV infection should receive regular surveillance for undiagnosed HIV infection when they present with herpes zoster. Copyright © 2015. Published by Elsevier B.V.

  17. Bioreactor production of recombinant herpes simplex virus vectors.

    PubMed

    Knop, David R; Harrell, Heather

    2007-01-01

    Serotypical application of herpes simplex virus (HSV) vectors to gene therapy (type 1) and prophylactic vaccines (types 1 and 2) has garnered substantial clinical interest recently. HSV vectors and amplicons have also been employed as helper virus constructs for manufacture of the dependovirus adeno-associated virus (AAV). Large quantities of infectious HSV stocks are requisite for these therapeutic applications, requiring a scalable vector manufacturing and processing platform comprised of unit operations which accommodate the fragility of HSV. In this study, production of a replication deficient rHSV-1 vector bearing the rep and cap genes of AAV-2 (denoted rHSV-rep2/cap2) was investigated. Adaptation of rHSV production from T225 flasks to a packed bed, fed-batch bioreactor permitted an 1100-fold increment in total vector production without a decrease in specific vector yield (pfu/cell). The fed-batch bioreactor system afforded a rHSV-rep2/cap2 vector recovery of 2.8 x 10(12) pfu. The recovered vector was concentrated by tangential flow filtration (TFF), permitting vector stocks to be formulated at greater than 1.5 x 10(9) pfu/mL.

  18. Nelfinavir Inhibits Maturation and Export of Herpes Simplex Virus 1

    PubMed Central

    Kalu, Nene N.; Desai, Prashant J.; Shirley, Courtney M.; Gibson, Wade; Dennis, Phillip A.

    2014-01-01

    ABSTRACT Nelfinavir (NFV) is an HIV-1 protease inhibitor with demonstrated antiviral activity against herpes simplex virus 1 (HSV-1) and several other herpesviruses. However, the stages of HSV-1 replication inhibited by NFV have not been explored. In this study, we investigated the effects of NFV on capsid assembly and envelopment. We confirmed the inhibitory effects of NFV on HSV-1 replication by plaque assay and found that treatment with NFV did not affect capsid assembly, activity of the HSV-1 maturational protease, or formation of DNA-containing capsids in the nucleus. Confocal and electron microscopy studies showed that these capsids were transported to the cytoplasm but failed to complete secondary envelopment and subsequent exit from the cell. Consistent with the microscopy results, a light-scattering band corresponding to enveloped virions was not evident following sucrose gradient rate-velocity separation of lysates from drug-treated cells. Evidence of a possibly related effect of NFV on viral glycoprotein maturation was also discovered. NFV also inhibited the replication of an HSV-1 thymidine kinase mutant resistant to nucleoside analogues such as acyclovir. Given that NFV is neither a nucleoside mimic nor a known inhibitor of nucleic acid synthesis, this was expected and suggests its potential as a coinhibitor or alternate antiviral therapeutic agent in cases of resistance. IMPORTANCE Nelfinavir (NFV) is a clinically important antiviral drug that inhibits production of infectious HIV. It was reported to inhibit herpesviruses in cell culture. Herpes simplex virus 1 (HSV-1) infections are common and often associated with several diseases. The studies we describe here confirm and extend earlier findings by investigating how NFV interferes with HSV-1 replication. We show that early steps in virus formation (e.g., assembly of DNA-containing capsids in the nucleus and their movement into the cytoplasm) appear to be unaffected by NFV, whereas later steps (e

  19. Guidelines for the management of herpes simplex virus in pregnancy.

    PubMed

    Money, Deborah; Steben, Marc

    2008-06-01

    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.

  20. Performance of HerpeSelect and Kalon Assays in Detection of Antibodies to Herpes Simplex Virus Type 2▿

    PubMed Central

    LeGoff, Jérôme; Mayaud, Philippe; Gresenguet, Gérard; Weiss, Helen A.; Nzambi, Khonde; Frost, Eric; Pepin, Jacques; Belec, Laurent

    2008-01-01

    The performances of commercial enzyme-linked immunosorbent assays (ELISAs) in detecting herpes simplex virus type 2 (HSV-2) antibodies have been inconsistent for African and human immunodeficiency virus (HIV)-positive populations. We compared the performances of the HerpeSelect and Kalon glycoprotein G2 ELISAs for patients with genital ulcer disease in Ghana and the Central African Republic. Sera from 434 women were tested with the HerpeSelect assay, and a subsample (n = 199) was tested by the Kalon assay. Ulcer swabs and cervicovaginal lavage samples were tested for HSV-2 DNA by PCR. HSV-2-seronegative women with detectable genital HSV-2 DNA were retested for HSV-2 antibodies 14 and 28 days later by the two ELISAs. A total of 346 (80%) women were positive by HerpeSelect at baseline, and 225 (54%) had detectable genital (lesional or cervicovaginal) HSV-2 DNA. Sixty-six (19%) HerpeSelect-positive samples had low-positive index values (1.1 to 3.5), and 58% of these samples had detectable genital HSV-2 DNA. Global agreement between the two serological assays was 86%. Concordance was high (99%) for sera that were negative by HerpeSelect or had high index values (>3.5). Defining infection detected by HSV-2 DNA PCR and/or Kalon assay as true infection, 71% of sera with low-positive index values were associated with true HSV-2 infection. Twenty-five women were identified as having nonprimary first-episode genital HSV-2 infection. Rates of HSV-2 seroconversion at day 14 were 77% (10/13 patients) by HerpeSelect assay and 23% (3/13 patients) by Kalon assay, with four additional seroconversions detected by Kalon assay at day 28. HIV serostatus did not influence assay performance. Low index values obtained with the HerpeSelect assay may correspond to true HSV-2 infection, in particular to nonprimary first episodes of genital HSV-2 infection, and need to be interpreted in the context of clinical history. PMID:18385443

  1. Performance of HerpeSelect and Kalon assays in detection of antibodies to herpes simplex virus type 2.

    PubMed

    LeGoff, Jérôme; Mayaud, Philippe; Gresenguet, Gérard; Weiss, Helen A; Nzambi, Khonde; Frost, Eric; Pepin, Jacques; Belec, Laurent

    2008-06-01

    The performances of commercial enzyme-linked immunosorbent assays (ELISAs) in detecting herpes simplex virus type 2 (HSV-2) antibodies have been inconsistent for African and human immunodeficiency virus (HIV)-positive populations. We compared the performances of the HerpeSelect and Kalon glycoprotein G2 ELISAs for patients with genital ulcer disease in Ghana and the Central African Republic. Sera from 434 women were tested with the HerpeSelect assay, and a subsample (n = 199) was tested by the Kalon assay. Ulcer swabs and cervicovaginal lavage samples were tested for HSV-2 DNA by PCR. HSV-2-seronegative women with detectable genital HSV-2 DNA were retested for HSV-2 antibodies 14 and 28 days later by the two ELISAs. A total of 346 (80%) women were positive by HerpeSelect at baseline, and 225 (54%) had detectable genital (lesional or cervicovaginal) HSV-2 DNA. Sixty-six (19%) HerpeSelect-positive samples had low-positive index values (1.1 to 3.5), and 58% of these samples had detectable genital HSV-2 DNA. Global agreement between the two serological assays was 86%. Concordance was high (99%) for sera that were negative by HerpeSelect or had high index values (>3.5). Defining infection detected by HSV-2 DNA PCR and/or Kalon assay as true infection, 71% of sera with low-positive index values were associated with true HSV-2 infection. Twenty-five women were identified as having nonprimary first-episode genital HSV-2 infection. Rates of HSV-2 seroconversion at day 14 were 77% (10/13 patients) by HerpeSelect assay and 23% (3/13 patients) by Kalon assay, with four additional seroconversions detected by Kalon assay at day 28. HIV serostatus did not influence assay performance. Low index values obtained with the HerpeSelect assay may correspond to true HSV-2 infection, in particular to nonprimary first episodes of genital HSV-2 infection, and need to be interpreted in the context of clinical history.

  2. Herpes virus reactivation by low-intensity diode and CO₂ lasers.

    PubMed

    Saleh, Hazem Mohammad; Shaker, Ahmed Samir; Saafan, Ali Mohamed; Ibrahim, Adel Khalil

    2011-02-01

    The herpes virus enters into latency after symptomatic or asymptomatic herpetic infection. During latency, the virus has no impact on infected cells. However, internal or external stimuli, including certain lasers, can induce virus reactivation. The aim was to study the reactivation power of the low-intensity diode and CO(2) lasers on the latent herpes virus. The bovine herpesvirus 1 (BHV-1) was inoculated in either the nasal cavity or the lacrimal film of an animal model. Once the virus entered into latency, the trigeminal ganglia of animals were exposed to either a low-intensity diode or CO(2) laser. The reactivation of the virus was then explored by PCR, RT-PCR, and dot-blot hybridization on nasal or lacrimal swabs. The accuracy, sensitivity, and specificity of the aforementioned techniques were compared. The low-intensity diode laser reactivated the herpes virus less than the CO(2) laser. The nasally inoculated virus was more liable for reactivation by both lasers. PCR was considered as the standard method for the detection of the reactivated virus. Low-intensity diode and CO(2) lasers can induce herpes virus reactivation, with the diode laser less likely to reactivate the virus than the CO(2) laser.

  3. Paraneoplastic pemphigus and Castleman's disease in the setting of herpes simplex virus infection.

    PubMed

    Koch, Laine H; Layton, Christle J; Pilichowska, Monika; Stadecker, Miguel J; Barak, Orr

    2012-01-01

    A 14-year-old girl presented with a 3-week history of mucosal erosions, injected conjunctiva, dehydration, and respiratory distress. She had been treated with intravenous acyclovir for herpes simplex infection with positive herpes simplex virus immunoglobulin M and immunoglobulin G. Physical examination and imaging revealed a large abdominal mass. Incisional biopsy was obtained, and pathology demonstrated angiofollicular hyperplasia with hyalinized germinal centers and Castleman's syndrome-like features. Based on the mucosal erosions, herpes simplex virus serology and positive herpes simplex virus-1 direct fluorescent antibody, Castleman's disease secondary to overwhelming herpes simplex virus infection was the initial impression. The poor response to antivirals and subsequent development of a bullous eruption on the hands resulted in dermatology consultation. Skin biopsy was obtained from a bullae and revealed suprabasilar acantholysis with necrosis as well as upper dermal, perivascular, and interface infiltrate of lymphocytes and eosinophils. No viropathic changes were present. Direct immunofluorescence was significant for immunoglobulin G deposition intercellularly and along the dermoepidermal junction and focal trace C3 deposition along the dermoepidermal junction consistent with paraneoplastic pemphigus, later confirmed by indirect immunofluorescence. We report this case of paraneoplastic pemphigus secondary to Castleman's syndrome confounded by herpes simplex virus-1 positive mucosal erosions.

  4. The role of human papilloma virus and herpes viruses in the etiology of nasal polyposis.

    PubMed

    Koçoğlu, Mücahide Esra; Mengeloğlu, Fırat Zafer; Apuhan, Tayfun; Özsoy, Şeyda; Yilmaz, Beyhan

    2016-02-17

    The aim of this study was to investigate the etiological role of human papilloma virus (HPV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6) and -7 (HHV-7) in the occurrence of nasal polyposis. Nasal polyp samples from 30 patients with nasal polyposis and normal nasal mucosa from 10 patients without nasal polyps were obtained. DNA was extracted from tissues. Real-time polymerase chain reaction was performed for all runs. No HSV-1, HSV-2, or VZV was detected in the samples. Among the patient samples, EBV and HHV-7 DNA were detected in 18 (60%), HHV-6 was detected in 20 (66.7%), and HPV was detected in 4 (13.3%) samples. Among the controls, CMV DNA was positive in one (10%). EBV was positive in 5 (50%), HHV-6 and HHV-7 were positive in 7 (70%), and HPV was positive in 2 (20%) samples. No significant difference was found among the groups with any test in terms of positivity. The association of Herpesviridae and HPV with the pathogenesis of nasal polyps was investigated in this study and no relationship was found. Thus, these viruses do not play a significant role in the formation of nasal polyps.

  5. Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs

    PubMed Central

    Braidwood, Lynne; Graham, Sheila V; Graham, Alex; Conner, Joe

    2013-01-01

    Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs) have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVexGM-CSF]), is almost complete, with extremely positive early results reported. Intuitively, therapeutically beneficial interactions between oHSV and chemotherapeutic and targeted therapeutic drugs would be limited as the virus requires actively dividing cells for maximum replication efficiency and most anticancer agents are cytotoxic or cytostatic. However, combinations of such agents display a range of responses, with antagonistic, additive, or, perhaps most surprisingly, synergistic enhancement of antitumor activity. When synergistic interactions in cancer cell killing are observed, chemotherapy dose reductions that achieve the same overall efficacy may be possible, resulting in a valuable reduction of adverse side effects. Therefore, the combination of an oHSV with “standard-of-care” drugs makes a logical and reasonable approach to improved therapy, and the addition of a targeted oncolytic therapy with “standard-of-care” drugs merits further investigation, both preclinically and in the clinic. Numerous publications report such studies of oncolytic HSV in combination with other drugs, and we review their findings here. Viral interactions with cellular hosts are complex and frequently involve intracellular signaling networks, thus creating diverse opportunities for synergistic or additive combinations with many anticancer drugs. We discuss potential mechanisms that may lead to synergistic interactions

  6. Herpes simplex virus type 1 encephalitis in acquired immunodeficiency syndrome.

    PubMed

    Chrétien, F; Bélec, L; Hilton, D A; Flament-Saillour, M; Guillon, F; Wingertsmann, L; Baudrimont, M; de Truchis, P; Keohane, C; Vital, C; Love, S; Gray, F

    1996-10-01

    Herpes simplex (HSV) infection of the central nervous system is uncommon in AIDS and usually has an atypical topography. This review is centred around the case of a 49-year-old homosexual patient with AIDS who died from diffuse encephalopathy. Neuropathological examination revealed necrotic and haemorrhagic changes involving both temporal lobes, insulae and cingulate gyri. Cowdry type A intranuclear inclusion bodies were abundant but inflammation was minimal. Electron microscopy confirmed characteristic herpes virus particles. Immunocyto-chemistry was positive for HSV type 1 and 2. In situ hybridization and PCR, however, were positive for HSV type 1 but excluded HSV type 2. There was associated cytomegalovirus ventriculitis but clearly separated from HSV encephalitis. There were no histological features of HIV encephalitis and HIV could not be demonstrated by immunocytochemistry or by PCR to demonstrate proviral DNA. Apoptotic neurons were numerous in areas with a severe macrophage reaction. Only two pathological cases with characteristic limbic distribution and necrotic haemorrhagic histologic have been reported previously. The rarity of these reports suggests that in advanced AIDS, the immune reaction causing a typical necrotizing encephalitis cannot be mounted. Distinction between HSV type 1 and 2 infection may be difficult by immunocytochemistry and usually requires in situ hybridization, tissue culture or PCR. In AIDS patients, HSV-1 has been identified as responsible for encephalitis whereas HSV-2 has been more responsible for myelitis. Associated productive HIV infection of the CNS was found in none of the cases. In contrast, cytomegalovirus encephalitis was found in nine of 11 cases of AIDS-associated HSV encephalitis.

  7. Preparation of herpes simplex virus-infected primary neurons for transmission electron microscopy.

    PubMed

    Miranda-Saksena, Monica; Boadle, Ross; Cunningham, Anthony L

    2014-01-01

    Transmission electron microscopy (TEM) provides the resolution necessary to identify both viruses and subcellular components of cells infected with many types of viruses, including herpes simplex virus. Recognized as a powerful tool in both diagnostic and research-based virology laboratories, TEM has made possible the identification of new viruses and has contributed to the elucidation of virus life cycle and virus-host cell interaction. Whilst there are many sample preparation techniques for TEM, conventional processing using chemical fixation and resin embedding remains a useful technique, available in virtually all EM laboratories, for studying virus/cell ultrastructure. In this chapter, we describe the preparation of herpes simplex virus-infected primary neurons, grown on plastic cover slips, to allow sectioning of neurons and axons in their growth plane. This technique allows TEM examination of cell bodies, axons, growth cones, and varicosities, providing powerful insights into virus-cell interaction.

  8. Inhibitors of nucleotidyltransferase superfamily enzymes suppress herpes simplex virus replication.

    PubMed

    Tavis, John E; Wang, Hong; Tollefson, Ann E; Ying, Baoling; Korom, Maria; Cheng, Xiaohong; Cao, Feng; Davis, Katie L; Wold, William S M; Morrison, Lynda A

    2014-12-01

    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 compounds in two chemical families inhibited HSV replication in Vero and human foreskin fibroblast cells as well as the approved drug acyclovir did. The compounds had 50% effective concentration values as low as 0.22 μM with negligible cytotoxicity in the assays employed. The inhibitors suppressed accumulation of viral genomes and infectious particles and blocked events in the viral replication cycle before and during viral DNA replication. Acyclovir-resistant mutants of HSV-1 and HSV-2 remained highly sensitive to the NTS inhibitors. Five of six NTS inhibitors of the HSVs also blocked replication of another herpesvirus pathogen, human cytomegalovirus. Therefore, NTS enzyme inhibitors are promising candidates for new herpesvirus treatments that may have broad efficacy against members of the herpesvirus family.

  9. Cervical cancer: is herpes simplex virus type II a cofactor?

    PubMed Central

    Jones, C

    1995-01-01

    In many ways, cervical cancer behaves as a sexually transmitted disease. The major risk factors are multiple sexual partners and early onset of sexual activity. Although high-risk types of human papillomaviruses (HPV) play an important role in the development of nearly all cases of cervical cancer, other sexually transmitted infectious agents may be cofactors. Herpes simplex virus type 2 (HSV-2) is transmitted primarily by sexual contact and therefore has been implicated as a risk factor. Several independent studies suggest that HSV-2 infections correlate with a higher than normal incidence of cervical cancer. In contrast, other epidemiological studies have concluded that infection with HSV-2 is not a major risk factor. Two separate transforming domains have been identified within the HSV-2 genome, but continued viral gene expression apparently is not necessary for neoplastic transformation. HSV infections lead to unscheduled cellular DNA synthesis, chromosomal amplifications, and mutations. These observations suggest that HSV-2 is not a typical DNA tumor virus. It is hypothesized that persistent or abortive infections induce permanent genetic alterations that interfere with differentiation of cervical epithelium and subsequently induce abnormal proliferation. Thus, HSV-2 may be a cofactor in some but not all cases of cervical cancer. PMID:8665469

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

    PubMed Central

    2017-01-01

    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. PMID:28255301

  11. Herpes simplex virus induces the replication of foreign DNA

    SciTech Connect

    Danovich, R.M.; Frenkel, N.

    1988-08-01

    Plasmids containing the simian virus 40 (SV40) DNA replication origin and the large T gene are replicated in Vero monkey cells but not in rabbit skin cells. Efficient replication of the plasmids was observed in rabbit cells infected with herpes simplex virus type 1 (HSV-1) and HSV-2. The HSV-induced replication required the large T antigen and the SV40 replication origin. However, it produced concatemeric molecules resembling replicative intermediates of HSV DNA and was sensitive to phosphonoacetate at concentrations known to inhibit the HSV DNA polymerase. Therefore, it involved the HSV DNA polymerase itself or a viral gene product(s) which was expressed following the replication of HSV DNA. Analyses of test plasmids lacking SV40 or HSV DNA sequences showed that, under some conditions. HSV also induced low-level replication of test plasmids containing no known eucaryotic replication origins. Together, these results show that HSV induces a DNA replicative activity which amplifies foreign DNA. The relevance of these findings to the putative transforming potential of HSV is discussed.

  12. Bell palsy and herpes simplex virus: identification of viral DNA in endoneurial fluid and muscle.

    PubMed

    Murakami, S; Mizobuchi, M; Nakashiro, Y; Doi, T; Hato, N; Yanagihara, N

    1996-01-01

    To determine whether herpes simplex virus type 1 (HSV-1) causes Bell palsy. Prospective study. University inpatient service. 14 patients with Bell palsy, 9 patients with the Ramsay-Hunt syndrome, and 12 other controls. Viral genomes of HSV-1, varicella-zoster virus, and Epstein-Barr virus were analyzed in clinical samples of facial nerve endoneurial fluid and posterior auricular muscle using polymerase chain reaction (PCR) followed by hybridization with Southern blot analysis. Herpes simplex virus type 1 genomes were detected in 11 of 14 patients (79%) with Bell palsy but not in patients with the Ramsay-Hunt syndrome or in other controls. The nucleotide sequences of the PCR fragments were identical to those of the HSV-1 genome. Herpes simplex virus type 1 is the major etiologic agent in Bell palsy.

  13. Recurrent Transcortical Motor Aphasia—Another CNS Infectious Syndrome Associated with Herpes Virus Infection

    PubMed Central

    Govindarajan, Raghav; Salgado, Efrain

    2016-01-01

    Herpes simplex encephalitis is an acute/subacute illness that causes both general and focal signs of cerebral dysfunction with fever, headache, and confusion as cardinal features. Recurrent herpes simplex meningitis, also known as Mollaret’s meningitis, is another manifestation of central nervous system herpetic infection with recurrent episodes of fever, headache, and nuchal rigidity associated with cerebrospinal fluid (CSF) evidence of active herpes simplex infection. Bell’s palsy is yet another manifestation of a herpes virus infection in at least some reported cases documented by CSF analysis. We report a case of a 70-year-old male who presented with acute transcortical motor aphasia initiating a stroke work-up that was negative. Physical examination revealed genital vesicles, and the CSF was consistent with active herpes simplex infection. PMID:26958155

  14. Human immunodeficiency virus, herpes virus infections, and pulmonary vascular disease.

    PubMed

    Flores, Sonia C; Almodovar, Sharilyn

    2013-01-01

    The following state-of-the-art seminar was delivered as part of the Aspen Lung Conference on Pulmonary Hypertension and Vascular Diseases held in Aspen, Colorado in June 2012. This paper will summarize the lecture and present results from a nonhuman primate model of infection with Simian (Human) Immunodeficiency Virus - nef chimeric virions as well as the idea that polymorphisms in the HIV-1 nef gene may be driving the immune response that results in exuberant inflammation and aberrant endothelial cell (EC) function. We will present data gathered from primary HIV nef isolates where we tested the biological consequences of these polymorphisms and how their presence in human populations may predict patients at risk for developing this disease. In this article, we also discuss how a dysregulated immune system, in conjunction with a viral infection, could contribute to pulmonary arterial hypertension (PAH). Both autoimmune diseases and some viruses are associated with defects in the immune system, primarily in the function of regulatory T cells. These T-cell defects may be a common pathway in the formation of plexiform lesions. Regardless of the route by which viruses may lead to PAH, it is important to recognize their role in this rare disease.

  15. Human immunodeficiency virus, herpes virus infections, and pulmonary vascular disease

    PubMed Central

    Flores, Sonia C.; Almodovar, Sharilyn

    2013-01-01

    The following state-of-the-art seminar was delivered as part of the Aspen Lung Conference on Pulmonary Hypertension and Vascular Diseases held in Aspen, Colorado in June 2012. This paper will summarize the lecture and present results from a nonhuman primate model of infection with Simian (Human) Immunodeficiency Virus - nef chimeric virions as well as the idea that polymorphisms in the HIV-1 nef gene may be driving the immune response that results in exuberant inflammation and aberrant endothelial cell (EC) function. We will present data gathered from primary HIV nef isolates where we tested the biological consequences of these polymorphisms and how their presence in human populations may predict patients at risk for developing this disease. In this article, we also discuss how a dysregulated immune system, in conjunction with a viral infection, could contribute to pulmonary arterial hypertension (PAH). Both autoimmune diseases and some viruses are associated with defects in the immune system, primarily in the function of regulatory T cells. These T-cell defects may be a common pathway in the formation of plexiform lesions. Regardless of the route by which viruses may lead to PAH, it is important to recognize their role in this rare disease. PMID:23662195

  16. Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro.

    PubMed

    Schuhmacher, A; Reichling, J; Schnitzler, P

    2003-01-01

    The virucidal effect of peppermint oil, the essential oil of Mentha piperita, against herpes simplex virus was examined. The inhibitory activity against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) was tested in vitro on RC-37 cells using a plaque reduction assay. The 50% inhibitory concentration (IC50) of peppermint oil for herpes simplex virus plaque formation was determined at 0.002% and 0.0008% for HSV-1 and HSV-2, respectively. Peppermint oil exhibited high levels of virucidal activity against HSV-1 and HSV-2 in viral suspension tests. At noncytotoxic concentrations of the oil, plaque formation was significantly reduced by 82% and 92% for HSV-1 and HSV-2, respectively. Higher concentrations of peppermint oil reduced viral titers of both herpesviruses by more than 90%. A clearly time-dependent activity could be demonstrated, after 3 h of incubation of herpes simplex virus with peppermint oil an antiviral activity of about 99% could be demonstrated. In order to determine the mode of antiviral action of the essential oil, peppermint oil was added at different times to the cells or viruses during infection. Both herpesviruses were significantly inhibited when herpes simplex virus was pretreated with the essential oil prior to adsorption. These results indicate that peppermint oil affected the virus before adsorption, but not after penetration into the host cell. Thus this essential oil is capable to exert a direct virucidal effect on HSV. Peppermint oil is also active against an acyclovir resistant strain of HSV-1 (HSV-1-ACV(res)), plaque formation was significantly reduced by 99%. Considering the lipophilic nature of the oil which enables it to penetrate the skin, peppermint oil might be suitable for topical therapeutic use as virucidal agent in recurrent herpes infection.

  17. [Herpes simplex virus vaccine studies: from past to present].

    PubMed

    Us, Dürdal

    2006-10-01

    The dramatical increase in the prevalence of Herpes simplex virus (HSV) infections and the significant physical and psychosocial morbidity of HSV type 2 infections, generate the need for an efficacious HSV vaccine. The most important properties of HSVs that should be targeted for a successful vaccine are neuronal invasion, latency and reactivation in spite of specific host immune responses. The major expectation for an ideal HSV vaccine candidate is to induce sterilizing immunity, which must be effective at all portals of HSV entry; to prevent or reduce the symptomatic disease and to eliminate or at least to limit the asymptomatic viral shedding. The first vaccine studies have began in the 1920s and in the intervening eight decades there have been many attempts to develop an effective one. Although encouraging findings came from experiments in various animal models, human studies have been disappointing, unfortunately. The vaccine strategies that have undergone clinical evaluation until today included autoinoculation of live HSV, whole inactivated vaccines, attenuated live virus vaccines, modified live virus subunit vaccines, cell culture-derived subunit vaccines, recombinant subunit (glycoprotein) vaccines, DISC (Disabled Infectious Single Cycle) virus vaccines, viral vectors and naked DNA vaccines. In most of the clinical studies the failure of HSV vaccines in spite of inducing very high levels of specific neutralizing antibodies have emphasized that cell-mediated immune response, especially Thl type immunity is important in preventing both primary disease and recurrences with HSV, rather than humoral response. The most hopeful result was obtained with HSV-2 gD and alum/MPL vaccine in clinical studies. This vaccine was found 74% effective in preventing genital disease in HSV seronegative women but was not effective in men or seropositive women. In recent years it is possible to genetically engineer HSV to produce a vaccine strain that is protective without

  18. The cycle of human herpes simplex virus infection: virus transport and immune control.

    PubMed

    Cunningham, Anthony L; Diefenbach, Russell J; Miranda-Saksena, Monica; Bosnjak, Lidija; Kim, Min; Jones, Cheryl; Douglas, Mark W

    2006-09-15

    After infection of skin or mucosa, herpes simplex virus enters the sensory nerve endings and is conveyed by retrograde axonal transport to the dorsal root ganglion, where the virus develops lifelong latency. Intermittent reactivation, which is spontaneous in humans, leads to anterograde transport of virus particles and proteins to the skin or mucosa, where the virus is shed and/or causes disease. Immune control of viral infection and replication occurs at the level of skin or mucosa during initial or recurrent infection and also within the dorsal root ganglion, where immune mechanisms control latency and reactivation. This article examines current views on the mechanisms of retrograde and anterograde transport of the virus in axons and the mechanisms of innate and adaptive immunity that control infection in the skin or mucosa and in the dorsal root ganglion--in particular, the role of interferons, myeloid and plasmacytoid dendritic cells, CD4(+) and CD8(+) T cells, and interferon- gamma and other cytokines, including their significance in the development of vaccines for genital herpes.

  19. Herpes Simplex Virus 2 Infection Impacts Stress Granule Accumulation

    PubMed Central

    Finnen, Renée L.; Pangka, Kyle R.

    2012-01-01

    Interference with stress granule (SG) accumulation is gaining increased appreciation as a common strategy used by diverse viruses to facilitate their replication and to cope with translational arrest. Here, we examined the impact of infection by herpes simplex virus 2 (HSV-2) on SG accumulation by monitoring the localization of the SG components T cell internal antigen 1 (TIA-1), Ras-GTPase-activating SH3-domain-binding protein (G3BP), and poly(A)-binding protein (PABP). Our results indicate that SGs do not accumulate in HSV-2-infected cells and that HSV-2 can interfere with arsenite-induced SG accumulation early after infection. Surprisingly, SG accumulation was inhibited despite increased phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), implying that HSV-2 encodes previously unrecognized activities designed to maintain translation initiation downstream of eIF2α. SG accumulation was not inhibited in HSV-2-infected cells treated with pateamine A, an inducer that works independently of eIF2α phosphorylation. The SGs that accumulated following pateamine A treatment of infected cells contained G3BP and PABP but were largely devoid of TIA-1. We also identified novel nuclear structures containing TIA-1 that form late in infection. These structures contain the RNA binding protein 68-kDa Src-associated in mitosis (Sam68) and were noticeably absent in infected cells treated with inhibitors of viral DNA replication, suggesting that they arise as a result of late events in the virus replicative cycle. PMID:22623775

  20. Herpes simplex virus 2 infection impacts stress granule accumulation.

    PubMed

    Finnen, Renée L; Pangka, Kyle R; Banfield, Bruce W

    2012-08-01

    Interference with stress granule (SG) accumulation is gaining increased appreciation as a common strategy used by diverse viruses to facilitate their replication and to cope with translational arrest. Here, we examined the impact of infection by herpes simplex virus 2 (HSV-2) on SG accumulation by monitoring the localization of the SG components T cell internal antigen 1 (TIA-1), Ras-GTPase-activating SH3-domain-binding protein (G3BP), and poly(A)-binding protein (PABP). Our results indicate that SGs do not accumulate in HSV-2-infected cells and that HSV-2 can interfere with arsenite-induced SG accumulation early after infection. Surprisingly, SG accumulation was inhibited despite increased phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), implying that HSV-2 encodes previously unrecognized activities designed to maintain translation initiation downstream of eIF2α. SG accumulation was not inhibited in HSV-2-infected cells treated with pateamine A, an inducer that works independently of eIF2α phosphorylation. The SGs that accumulated following pateamine A treatment of infected cells contained G3BP and PABP but were largely devoid of TIA-1. We also identified novel nuclear structures containing TIA-1 that form late in infection. These structures contain the RNA binding protein 68-kDa Src-associated in mitosis (Sam68) and were noticeably absent in infected cells treated with inhibitors of viral DNA replication, suggesting that they arise as a result of late events in the virus replicative cycle.

  1. Identification and analysis of putative promoter motifs in bovine herpes virus.

    PubMed

    Kurjogi, Mahantesh Mallikrjun; Sanakal, Rajeshwari Danappa; Kaliwal, Basappa Basaveneppa

    2012-01-01

    The purpose of this study is to identify and analyse the putative promoter motifs in the bovine herpes virus which causes several diseases in cattle worldwide including bovine mastitis with large economic impact on dairy industry. Bovine mastitis caused due to virus is often neglected as bacterial infections are held mainly responsible for the disease. Therefore, in this in silico investigation with all the existing experimental data a total of 147 promoter were identified along with their sequences from three genome viz bovine herpes virus 1 (BHV), bovine herpes virus 4 and bovine herpes virus 5, out of which 39 promoters were from bovine herpes virus 4 (BHV 4), 95 from BHV1 and 13 from BHV5 and it was observed that BHV1 and BHV5 have a close evolutionary history. However, they belong to the same subfamily and size of the genome and GC% of BHV1 and BHV5 was almost equal and very high compare to that of BHV4. This analysis may help in designing the live attenuated vaccine against BHV causing bovine mastitis that reduces the incidence of bovine mastitis. Identification of promoters may also help in designing of expression vectors which help in better understanding of the regulation of gene expression. In the era of large genomics and proteomics prediction of promoters in the whole genome is crucial for the advancement of drug discovery and gene therapy.

  2. The use of FTIR microscopy for evaluation of herpes viruses infection development kinetics

    NASA Astrophysics Data System (ADS)

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

    2004-08-01

    The kinetics of Herpes simplex infection development was studied using an FTIR microscopy (FTIR-M) method. The family of herpes viruses includes several members like H. simplex types I and II (HSV I, II), Varicella zoster (VZV) viruses which are involved in various human and animal infections of different parts of the body. In our previous study, we found significant spectral differences between normal uninfected cells in cultures and cells infected with herpes viruses at early stages of the infection. In the present study, cells in cultures were infected with either HSV-I or VZV and at various times post-infection they were examined either by optical microscopy or by advanced FTIR-M. Spectroscopic measurements show a consistent decrease in the intensity of the carbohydrate peak in correlation with the viral infection development, observed by optical microscopy. This decrease in cellular carbohydrate level was used as indicator for herpes viruses infection kinetics. This parameter could be used as a basis for applying a spectroscopic method for the evaluation of herpes virus infection development. Our results show also that the development kinetics of viral infection has an exponential character for these viruses.

  3. A system for isolation, transport and storage of herpes simplex viruses.

    PubMed

    Skinner, G R; Billstrom, M A; Randall, S; Ahmad, A; Patel, S; Davies, J; Deane, A

    1997-04-01

    A major difficulty with diagnostic virus isolation concerns the relative thermolability of certain viruses, e.g. herpes simplex virus type 2, which may, therefore, lose infectivity during transport to the laboratory. This study describes a system of virus isolation and transport, which depends on direct inoculation at the bedside or clinic, to a monolayer or suspension of susceptible cells with subsequent incubation for 10 h at approximately 32 degrees C, whereupon the newly synthesised virus becomes very stable if the cells are subsequently maintained at room temperature. This system was found to increase the sensitivity of isolation of herpes simplex virus, particularly under conditions of asymptomatic virus excretion or if there was significant delay in transportation of clinical samples to the virus laboratory. It is envisaged that this system will allow clinical self-sampling by the patient with application to epidemiological surveys in both the developed and underdeveloped world.

  4. The relative infrequency and low levels of neutralising and immunoprecipitating antibody to herpes simplex viruses types 1 and 2 in patients with a history of recurrent herpes genitalis.

    PubMed

    Woodman, C B; Stocker, D; Sugrue, D; Desberbasques, M; Hartley, C E; Fuller, A; Buchan, A; Skinner, G R

    1983-01-01

    Twenty-seven per cent of 70 patients with a history of recurrent herpes genitalis but no concomitant history of recurrent oral or peri-genital disease, had no detectable neutralising antibody against type 1 or type 2 herpes simplex virus; the prevalence and levels of neutralising antibody were similar to 53 patients with no history of herpetic disease and significantly lower than 67 patients with a history of recurrent herpes genitalis in association with oral or peri-genital disease all of whom had neutralising antibody against both virus types. There were similar differences between groups for immunoprecipitating antibody where 80% of patients were herpes genitalis alone had no detectable immunoprecipitating antibody. The results indicate that the failure to detect immunising and immunoprecipitating antibody in an individual's serum is compatible with a long and even severe history of recurrent herpes genitalis and consequently that the development of neutralising antibody does not necessarily indicate an episode of primary herpetic disease.

  5. Genital Herpes

    MedlinePlus

    ... herpes is HSV-2. HSV-1 usually causes cold sores that appear on the mouth, lips, and eyes, but it is becoming more common as a cause of genital herpes, especially in young women. How common is the herpes virus? At least 50 million people in the United ...

  6. Infection with human immunodeficiency virus, herpes simplex virus type 2, and human herpes virus 8 in remote villages of southwestern Papua New Guinea.

    PubMed

    Suligoi, B; Danaya, R T; Sarmati, L; Owen, I L; Boros, S; Pozio, E; Andreoni, M; Rezza, G

    2005-01-01

    To investigate the spread of human immunodeficiency virus (HIV) and other sexually transmitted viruses, two serosurveys (the first in 1999 among 56 adults and the second in 2001 among 351 adults) were conducted in remote villages of the southwestern part of Papua New Guinea. Only one individual was positive for antibodies to HIV. In 2001, the seroprevalence of human herpes virus 8 (HHV-8) was 32.2%, and the seroprevalence of herpes simplex virus type 2 (HSV-2) was 27.4%. Both prevalence rates increased with age, and were lower in the villages near the Bensbach River. The seropositivity of HSV-2 was independently correlated with HHV-8 infection. Our data show that the inhabitants of the southwestern region of Papua New Guinea currently experience an extremely low circulation of HIV. However, the high prevalence of infectious agents that can be sexually transmitted, such as HSV-2 and to a lesser extent HHV-8, indicates the presence of behavioral patterns that may facilitate the spread of HIV in this area of currently low endemicity.

  7. Latency of Herpes Simplex Virus in Absence of Neutralizing Antibody: Model for Reactivation

    NASA Astrophysics Data System (ADS)

    Sekizawa, Tsuyoshi; Openshaw, Harry; Wohlenberg, Charles; Notkins, Abner Louis

    1980-11-01

    Mice inoculated with herpes simplex virus (type 1) by the lip or corneal route and then passively immunized with rabbit antibody to herpes simplex virus developed a latent infection in the trigeminal ganglia within 96 hours. Neutralizing antibody to herpes simplex virus was cleared from the circulation and could not be detected in most of these mice after 2 months. Examination of ganglia from the antibody-negative mice revealed latent virus in over 90 percent of the animals, indicating that serum neutralizing antibody is not necessary to maintain the latent state. When the lips or corneas of these mice were traumatized, viral reactivation occurred in up to 90 percent of the mice, as demonstrated by the appearance of neutralizing antibody. This study provides a model for identifying factors that trigger viral reactivation.

  8. Chronic eosinophilic dermatitis associated with persistent feline herpes virus infection in cheetahs (Acinonyx jubatus).

    PubMed

    Munson, L; Wack, R; Duncan, M; Montali, R J; Boon, D; Stalis, I; Crawshaw, G J; Cameron, K N; Mortenson, J; Citino, S; Zuba, J; Junge, R E

    2004-03-01

    A chronic ulcerative and eosinophilic dermatitis occurred in 20 captive cheetahs (Acinonyx jubatus) with persistent feline herpes virus 1 (FHV1) infection. Affected animals had erythematous, ulcerated plaques primarily on the face and forelegs in sites of contact with lachrymal and salivary secretions. The dermatitis was characterized by dense infiltrates of eosinophils and plasma cells and pseudoepitheliomatous hyperplasia. Rare keratinocytes within the lesions had nuclei with marginated chromatin and small eosinophilic inclusions composed of herpes virus nucleocapsids. Virus isolated from lesions was confirmed to be FHV1. Lesions persisted and progressed unless removed by cryoexcision. The occurrence of this unusual reaction to FHV1 in approximately 5% of captive North American cheetahs suggests a species propensity for a Th2-dominant response to herpes virus infection. This atypical immune reaction may indicate a heritable trait or modulation of the immune response by other factors such as chronic stress.

  9. Bell's palsy and herpes viruses: to (acyclo)vir or not to (acyclo)vir?

    PubMed

    Steiner, I; Mattan, Y

    1999-11-15

    The majority of peripheral seventh cranial nerve palsy cases remain without an identified etiology and will eventually be diagnosed as idiopathic or Bell's palsy. Some features of this condition may be characteristic of a viral infection. Indeed, several herpes viruses have been implicated as potential causative pathogens. Besides varicella-zoster virus, shown to cause Bell's palsy under the Ramsay-Hunt syndrome, recent years have seen an increased interest and focus on the possible herpes simplex virus type 1 (HSV-1) etiology in idiopathic facial paralysis. We review the clinical, biological and virological basis for the potential herpetic cause of Bell's palsy and the rational for antiviral therapy in this condition.

  10. Influence of herpes simplex virus infection on benzo(a)pyrene metabolism in monkey kidney cells

    SciTech Connect

    Degenhardt, J.H.; Whitcomb, B.; Hall, M.R.

    1984-01-01

    Current research in our laboratory is designed to investigate the intracellular interactions of BP with oncogenic DNA viruses of animals and humans. In this study, our purpose was to determine whether BP is metabolized in herpes simplex virus type 2 (HSV-2) infected cells and whether HSV-2 infection affects intracellular levels of the aryl hydrocarbon hydroxylase system necessary for BP metabolism.

  11. Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques.

    PubMed

    Wozniak, M A; Mee, A P; Itzhaki, R F

    2009-01-01

    The brains of Alzheimer's disease sufferers are characterized by amyloid plaques and neurofibrillary tangles. However, the cause(s) of these features and those of the disease are unknown, in sporadic cases. We previously showed that herpes simplex virus type 1 is a strong risk factor for Alzheimer's disease when in the brains of possessors of the type 4 allele of the apolipoprotein E gene (APOE-epsilon4), and that beta-amyloid, the main component of plaques, accumulates in herpes simplex virus type 1-infected cell cultures and mouse brain. The present study aimed to elucidate the relationship of the virus to plaques by determining their proximity in human brain sections. We used in situ polymerase chain reaction to detect herpes simplex virus type 1 DNA, and immunohistochemistry or thioflavin S staining to detect amyloid plaques. We discovered a striking localization of herpes simplex virus type 1 DNA within plaques: in Alzheimer's disease brains, 90% of the plaques contained the viral DNA and 72% of the DNA was associated with plaques; in aged normal brains, which contain amyloid plaques at a lower frequency, 80% of plaques contained herpes simplex virus type 1 DNA but only 24% of the viral DNA was plaque-associated (p < 0.001). We suggest that this is because in aged normal individuals, there is a lesser production and/or greater removal of beta-amyloid (Abeta), so that less of the viral DNA is seen to be associated with Abeta in the brain. Our present data, together with our finding of Abeta accumulation in herpes simplex virus type 1-infected cells and mouse brain, suggest that this virus is a major cause of amyloid plaques and hence probably a significant aetiological factor in Alzheimer's disease. They point to the usage of antiviral agents to treat the disease and possibly of vaccination to prevent it.

  12. [Relationship between EB virus, Cytomegalo virus, herpes simplex virus and coxsackievirus infection and relapse of multiple sclerosis].

    PubMed

    Feng, Zi-jing; Zhao, Ri-guang; Wang, De-xin

    2008-12-01

    To study the relation between the recent active infection with Epstein-Barr virus, cytomegalovirus,herpes simplex virus-1, coxsackievirus B I-IV and the relapse of relapsing-remitting multiple sclerosis (RR MS). Using ELISA method, IgM antibodies to Epstein-Barr virus, cytomegalovirus, herpes simplex virus-1, coxsackievirus BI-IV in the plasma from 34 RR MS patients and 200 normal controls were detected. The rates of recent active infection with the above mentioned viruses of the patients and controls were compared.For patients group,comparison was also made between the clinical data of recent active infected patients and patients without recent active infection. There was no statistically significant difference in positive rates of positive rates of IgM antibodies against Epstein-Barr virus, cytomegalovirus, herpes simplex virus-1 and coxsackievirus BI, II, III or VI between the two groups. While there was statistically significant difference in positive rates of IgM antibodies to coxsackievirus B VI and V in the RR MS patients and those in the controls (being 3/34 and 0/200 P < 0.05; 2/34 and 0/200 P < 0.05, respectively). In the patient group, when patients who had active infection with any of the viruses were compared with those who had no active infection, no significant difference between them was found in terms of age, course, frequency, body temperature on admission, differential leukocyte count (neutrophilic granulocyte, lymphocyte and monocytes), use of glucocorticoids, and EDSS point value. There is a high rate of recent active infection with coxsackievirus B VI and V in RR MS patients at relapsing stage. While the recent virus active infection is unrelated to the severity of the symptoms.

  13. Clinical Correlates of Herpes Simplex Virus Viremia Among Hospitalized Adults

    PubMed Central

    Berrington, William R.; Jerome, Keith R.; Cook, Linda; Wald, Anna; Corey, Lawrence; Casper, Corey

    2009-01-01

    Background The quantification of herpes simplex virus (HSV) DNA from the peripheral blood is often used to evaluate patients suspected of having disseminated HSV infection. Few studies have examined the clinical correlates of HSV viremia among adults. Methods We conducted a retrospective analysis of blood samples sent to a reference molecular virology diagnostic facility at a university hospital for quantification of HSV DNA between October 2001 and June 2006. Medical records of patients with detectable HSV DNA were reviewed to abstract relevant clinical characteristics. Results HSV DNA was detected in 37 (4.0%) of 951 samples from 29 individual patients. 19 (65.5%) were >16 years of age, and detailed medical records were available for review from 13 (68.4%) of 19 adults patients. Of the 10 patients whose HSV infection was typed, 6 (60%) had HSV-2, 3 (30%) had HSV-1, and one had evidence of both HSV-1 and HSV-2 infection. All viremic patients were treated with antiviral medications. The most common clinical findings were hepatitis (62%), fever (54%), CNS alterations (46%), skin lesions (38%), abdominal pain (31%), and sepsis (31%). Respiratory failure (23%) was uncommon. Patients with HSV viremia were observed to have a high mortality rate (6 of 10 immunocompromised and 1 of 3 immunocompetent individuals). Conclusions HSV viremia may be associated with a variety of morbid signs and symptoms in hospitalized immunocompetent and immunocompromised adults, and is associated with high rates of mortality, though causality can only be determined by additional studies. PMID:19807272

  14. Extracts and molecules from medicinal plants against herpes simplex viruses.

    PubMed

    Khan, Mahmud Tareq Hassan; Ather, Arjumand; Thompson, Kenneth D; Gambari, Roberto

    2005-08-01

    Herpes simplex viruses (HSV-1 and -2) are important pathogens for humans, especially in the case of highly susceptible adults. Moreover, HSV-2 has been reported to be a high risk factor for HIV infection. Therefore, the discovery of novel anti-HSV drugs deserves great efforts. In this paper, we review anti-HSV substances from natural sources, including both extracts and pure compounds from herbal medicines, reported in studies from several laboratories. The role of traditional medicine for the development of anti-HSV compounds is also discussed. Interestingly, it was found that traditional medicines, like Ayurvedic, traditional Chinese (TCM), Chakma medicines, are good and potential sources for promising anti-HSV drugs. A second objective of this review is to discuss several anti-HSV compounds with respect to their structure-activity relationship (SAR). A large number of small molecules, like phenolics, polyphenols, terpenes (e.g., mono-, di-, tri-), flavonoids, sugar-containing compounds, were found to be promising anti-herpetic agents. Our major conclusion is that natural products from medicinal plant extracts are very important source of anti-HSV agents.

  15. Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid

    PubMed Central

    Aksyuk, Anastasia A.; Newcomb, William W.; Cheng, Naiqian; Winkler, Dennis C.; Fontana, Juan; Heymann, J. Bernard

    2015-01-01

    ABSTRACT The herpes simplex virus 1 (HSV-1) capsid is a massive particle (~200 MDa; 1,250-Å diameter) with T=16 icosahedral symmetry. It initially assembles as a procapsid with ~4,000 protein subunits of 11 different kinds. The procapsid undergoes major changes in structure and composition as it matures, a process driven by proteolysis and expulsion of the internal scaffolding protein. Assembly also relies on an external scaffolding protein, the triplex, an α2β heterotrimer that coordinates neighboring capsomers in the procapsid and becomes a stabilizing clamp in the mature capsid. To investigate the mechanisms that regulate its assembly, we developed a novel isolation procedure for the metastable procapsid and collected a large set of cryo-electron microscopy data. In addition to procapsids, these preparations contain maturation intermediates, which were distinguished by classifying the images and calculating a three-dimensional reconstruction for each class. Appraisal of the procapsid structure led to a new model for assembly; in it, the protomer (assembly unit) consists of one triplex, surrounded by three major capsid protein (MCP) subunits. The model exploits the triplexes’ departure from 3-fold symmetry to explain the highly skewed MCP hexamers, the triplex orientations at each 3-fold site, and the T=16 architecture. These observations also yielded new insights into maturation. PMID:26443463

  16. Evolution and Diversity in Human Herpes Simplex Virus Genomes

    PubMed Central

    Gatherer, Derek; Ochoa, Alejandro; Greenbaum, Benjamin; Dolan, Aidan; Bowden, Rory J.; Enquist, Lynn W.; Legendre, Matthieu; Davison, Andrew J.

    2014-01-01

    Herpes simplex virus 1 (HSV-1) causes a chronic, lifelong infection in >60% of adults. Multiple recent vaccine trials have failed, with viral diversity likely contributing to these failures. To understand HSV-1 diversity better, we comprehensively compared 20 newly sequenced viral genomes from China, Japan, Kenya, and South Korea with six previously sequenced genomes from the United States, Europe, and Japan. In this diverse collection of passaged strains, we found that one-fifth of the newly sequenced members share a gene deletion and one-third exhibit homopolymeric frameshift mutations (HFMs). Individual strains exhibit genotypic and potential phenotypic variation via HFMs, deletions, short sequence repeats, and single-nucleotide polymorphisms, although the protein sequence identity between strains exceeds 90% on average. In the first genome-scale analysis of positive selection in HSV-1, we found signs of selection in specific proteins and residues, including the fusion protein glycoprotein H. We also confirmed previous results suggesting that recombination has occurred with high frequency throughout the HSV-1 genome. Despite this, the HSV-1 strains analyzed clustered by geographic origin during whole-genome distance analysis. These data shed light on likely routes of HSV-1 adaptation to changing environments and will aid in the selection of vaccine antigens that are invariant worldwide. PMID:24227835

  17. Antiviral activity of Undaria pinnatifida against herpes simplex virus.

    PubMed

    Thompson, Kenneth D; Dragar, Charles

    2004-07-01

    The major component of an aqueous extract of the seaweed Undaria pinnati fi da has been identified previously as a galactofucan (GFS), a sulfated polysaccharide. The galactofucan was partially purified and the material tested in this study is 75% pure galactofucan sulfate. GFS was evaluated for antiviral activity against 32 clinical strains of herpes simplex virus (HSV): 14 strains of HSV-1 and 18 strains of HSV-2. Twelve strains (four HSV-1 and eight HSV-2) were resistant to acyclovir (ACV-R) and 20 strains (10 HSV-1 and 10 HSV-2) were susceptible to ACV (ACV-S). The median IC(50) of GFS for the 14 strains of HSV-1 was 32 micro g/mL. The median IC(50) of GFS for the 18 strains of HSV-2 was 0.5 micro g/mL. GFS is significantly more active against clinical strains of HSV-2 than HSV-1, p < 0.001. The mode of action of the GFS was shown to be the inhibition of viral binding and entry into the host cell. The cytotoxicity of GFS was >4.0 mg/mL in the neutral red dye uptake assay indicating that GFS is non-toxic in this assay.

  18. Herpes simplex virus encephalitis in Peru: a multicentre prospective study.

    PubMed

    Montano, S M; Mori, N; Nelson, C A; Ton, T G N; Celis, V; Ticona, E; Sihuincha, M; Tilley, D H; Kochel, T; Zunt, J R

    2016-06-01

    Herpes simplex virus (HSV) is one of the most commonly identified infectious aetiologies of encephalitis in North America and Europe. The epidemiology of encephalitis beyond these regions, however, is poorly defined. During 2009-2012 we enrolled 313 patients in a multicentre prospective study of encephalitis in Peru, 45 (14·4%) of whom had confirmed HSV infection. Of 38 patients with known HSV type, 84% had HSV-1 and 16% had HSV-2. Patients with HSV infection were significantly more likely to present in the summer months (44·4% vs. 20·0%, P = 0·003) and have nausea (60·0% vs. 39·8%, P = 0·01) and rash (15·6% vs. 5·3%, P = 0·01) compared to patients without HSV infection. These findings highlight differences in the epidemiology and clinical presentation of HSV encephalitis outside of the Northern Hemisphere that warrant further investigation. Furthermore, there is an urgent need for improved HSV diagnostic capacity and availability of intravenous acyclovir in Peru.

  19. Herpes Simplex Virus DNA Packaging without Measurable DNA Synthesis

    PubMed Central

    Church, Geoffrey A.; Dasgupta, Anindya; Wilson, Duncan W.

    1998-01-01

    Herpes simplex virus (HSV) type 1 DNA synthesis and packaging occur within the nuclei of infected cells; however, the extent to which the two processes are coupled remains unclear. Correct packaging is thought to be dependent upon DNA debranching or other repair processes, and such events commonly involve new DNA synthesis. Furthermore, the HSV UL15 gene product, essential for packaging, nevertheless localizes to sites of active DNA replication and may link the two events. It has previously been difficult to determine whether packaging requires concomitant DNA synthesis due to the complexity of these processes and of the viral life cycle; however, we have recently described a model system which simplifies the study of HSV assembly. Cells infected with HSV strain tsProt.A accumulate unpackaged capsids at the nonpermissive temperature of 39°C. Following release of the temperature block, these capsids proceed to package viral DNA in a single, synchronous wave. Here we report that, when DNA replication was inhibited prior to release of the temperature block, DNA packaging and later events in viral assembly nevertheless occurred at near-normal levels. We conclude that, under our conditions, HSV DNA packaging does not require detectable levels of DNA synthesis. PMID:9525593

  20. Stabilising the Herpes Simplex Virus capsid by DNA packaging

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

    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.

  2. Herpes simplex virus hepatitis after pediatric liver transplantation.

    PubMed

    Hori, T; Ogura, Y; Okamoto, S; Nakajima, A; Kami, K; Iwasaki, J; Yonekawa, Y; Ogawa, K; Oike, F; Takada, Y; Egawa, H; Nguyen, J H; Uemoto, S

    2010-08-01

    Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ transplanted recipients. Here, we present a thought-provoking case of HSV hepatitis in a high-risk recipient after living-related liver transplantation (LRLT). A 1-month-old female newborn infant was affected by HSV encephalitis. Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4 years of age. Viral infections were ruled out as the cause of FHF. Intensive care including plasma exchange (PE) was started, and the preoperative treatments for ABO incompatibility were performed. Thereafter, LRLT was performed emergently. Although strong immunosuppression for ABO incompatibility was continued after LRLT, antibody-mediated rejection (AMR) occurred on postoperative day (POD) 4. PE was repeated and improvements were obtained. However, liver dysfunction appeared on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV hepatitis, although the results of HSV DNA and antibody titer in blood sample did not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA) occurred and the plasma and immunoglobulin were replenished. Our pediatric recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated sepsis. We conclude that well considered therapy based on the real-time detection of HSV hepatitis is indispensable for the further improvements of outcome in HSV hepatitis after LRLT.

  3. "Armed" oncolytic herpes simplex viruses for brain tumor therapy.

    PubMed

    Todo, Tomoki

    2008-01-01

    Genetically engineered, conditionally replicating herpes simplex viruses type 1 (HSV-1) are promising therapeutic agents for brain tumors and other solid cancers. They can replicate in situ, spread and exhibit oncolytic activity via a direct cytocidal effect. One of the advantages of HSV-1 is the capacity to incorporate large and/or multiple transgenes within the viral genome. Oncolytic HSV-1 can therefore be "armed" to add certain functions. Recently, the field of armed oncolytic HSV-1 has drastically advanced, due to development of recombinant HSV-1 generation systems that utilize bacterial artificial chromosome and multiple DNA recombinases. Because antitumor immunity is induced in the course of oncolytic activities of HSV-1, transgenes encoding immunomodulatory molecules have been most frequently used for arming. Other armed oncolytic HSV-1 include those that express antiangiogenic factors, fusogenic membrane glycoproteins, suicide gene products, and proapoptotic proteins. Provided that the transgene product does not interfere with viral replication, such arming of oncolytic HSV-1 results in augmentation of antitumor efficacy. Immediate-early viral promoters are often used to control the arming transgenes, but strict-late viral promoters have been shown useful to restrict the expression in the late stage of viral replication when desirable. Some armed oncolytic HSV-1 have been created for the purpose of noninvasive in vivo imaging of viral infection and replication. Development of a wide variety of armed oncolytic HSV-1 will lead to an establishment of a new genre of therapy for brain tumors as well as other cancers.

  4. Protein sequences clustering of herpes virus by using Tribe Markov clustering (Tribe-MCL)

    NASA Astrophysics Data System (ADS)

    Bustamam, A.; Siswantining, T.; Febriyani, N. L.; Novitasari, I. D.; Cahyaningrum, R. D.

    2017-07-01

    The herpes virus can be found anywhere and one of the important characteristics is its ability to cause acute and chronic infection at certain times so as a result of the infection allows severe complications occurred. The herpes virus is composed of DNA containing protein and wrapped by glycoproteins. In this work, the Herpes viruses family is classified and analyzed by clustering their protein-sequence using Tribe Markov Clustering (Tribe-MCL) algorithm. Tribe-MCL is an efficient clustering method based on the theory of Markov chains, to classify protein families from protein sequences using pre-computed sequence similarity information. We implement the Tribe-MCL algorithm using an open source program of R. We select 24 protein sequences of Herpes virus obtained from NCBI database. The dataset consists of three types of glycoprotein B, F, and H. Each type has eight herpes virus that infected humans. Based on our simulation using different inflation factor r=1.5, 2, 3 we find a various number of the clusters results. The greater the inflation factor the greater the number of their clusters. Each protein will grouped together in the same type of protein.

  5. Mimicking herpes simplex virus 1 and herpes simplex virus 2 mucosal behavior in a well-characterized human genital organ culture.

    PubMed

    Steukers, Lennert; Weyers, Steven; Yang, Xiaoyun; Vandekerckhove, Annelies P; Glorieux, Sarah; Cornelissen, Maria; Van den Broeck, Wim; Temmerman, Marleen; Nauwynck, Hans J

    2014-07-15

    We developed and morphologically characterized a human genital mucosa explant model (endocervix and ectocervix/vagina) to mimic genital herpes infections caused by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Subsequent analysis of HSV entry receptor expression throughout the menstrual cycle in genital tissues was performed, and the evolution of HSV-1/-2 mucosal spread over time was assessed. Nectin-1 and -2 were expressed in all tissues during the entire menstrual cycle. Herpesvirus entry mediator expression was limited mainly to some connective tissue cells. Both HSV-1 and HSV-2 exhibited a plaque-wise mucosal spread across the basement membrane and induced prominent epithelial syncytia.

  6. Human cytomegalovirus function inhibits replication of herpes simplex virus

    SciTech Connect

    Cockley, K.D.; Shiraki, K.; Rapp, F.

    1988-01-01

    Human embryonic lung (HEL) cells infected with human cytomegalovirus (HCMV) restricted the replication of herpes simplex virus type 1 (HSV-1). A delay in HSV replication of 15 h as well as a consistent, almost 3 log inhibition of HSV replication in HCMV-infected cell cultures harvested 24 to 72 h after superinfection were observed compared with controls infected with HSV alone. Treatment of HCMV-infected HEL cells with cycloheximide (100 ..mu..g/ml) for 3 or 24 h was demonstrated effective in blocking HCMV protein synthesis, as shown by immunoprecipitation with HCMV antibody-positive polyvalent serum. Cycloheximide treatment of HCMV-infected HEL cells and removal of the cycloheximide block before superinfection inhibited HSV-1 replication more efficiently than non-drug-treated superinfected controls. HCMV DNA-negative temperature-sensitive mutants restricted HSV as efficiently as wild-type HCMV suggesting that immediate-early and/or early events which occur before viral DNA synthesis are sufficient for inhibition of HSV. Inhibition of HSV-1 in HCMV-infected HEL cells was unaffected by elevated temperature (40.5/sup 0/C). However, prior UV irradiation of HCMV removed the block to HSV replication, demonstrating the requirement for an active HCMV genome. HSV-2 replication was similarly inhibited in HCMV-infected HEL cells. Superinfection of HCMV-infected HEL cells with HSV-1 labeled with (/sup 3/H)thymidine provided evidence that the labeled virus could penetrate to the nucleus of cells after superinfection. Evidence for penetration of superinfecting HSV into HCMV-infected cells was also provided by blot hybridization of HSV DNA synthesized in cells infected with HSV alone versus superinfected cell cultures at 0 and 48 h after superinfection.

  7. Purification and structural characterization of herpes simplex virus glycoprotein C

    SciTech Connect

    Kikuchi, G.E.; Baker, S.A.; Merajver, S.D.; Coligan, J.E.; Levine, M.; Glorioso, J.C.; Nairn, R.

    1987-01-27

    Purification of herpes simplex virus glycoprotein C (gC) in microgram amounts yielded sufficient material for an analysis of its secondary structure. Purification was facilitated by using the mutant virus gC-3, which bears a point mutation that interrupts the putative hydrophobic membrane anchor sequence, causing the secretion of gC-3 protein into the cell culture medium. gC-3 protein was purified by size fractionation of concentrated culture medium from infected cells on a gel filtration column of Sephacryl S-200, followed by immunoaffinity chromatography on a column constructed of gC-specific monoclonal antibodies cross-linked to a protein A-Sepharose CL-4B matrix. Purified gC-3 had a molecular weight of 130,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the size expected for gC, was reactive with gC-specific monoclonal antibodies in protein immunoblots, and contained amino acid sequences characteristic of gC as determined by radiochemical amino acid microsequence analyses. Polyclonal antisera obtained from a rabbit immunized with gC-3 reacted with wild-type gC in immunoprecipitation, enzyme immunoassay, and immunoelectroblot (western blot) assays. Deglycosylation by treatment with trifluoromethanesulfonic acid reduced the molecular weight of gC-3 by approximately 35%. Analyses of both native and deglycosylated gC-3 by Raman spectroscopy showed that the native molecule consists of about 17%..cap alpha..-helix, 24% ..beta..-sheet, and 60% disordered secondary structures, whereas deglycosylated gC-3 consists of about 8% ..cap alpha..-helix, 10% ..beta..-sheet, 81% disordered structures. These data were in good agreement with the 11% ..cap alpha..-helix, 18% ..beta..-sheet, 61% ..beta..-turn, and 9% disordered structures calculated from Chou-Fasman analysis of the primary sequence of gC-3.

  8. Herpes simplex virus 2 infection: molecular association with HIV and novel microbicides to prevent disease.

    PubMed

    Suazo, Paula A; Tognarelli, Eduardo I; Kalergis, Alexis M; González, Pablo A

    2015-04-01

    Infection with herpes simplex viruses is one of the most ancient diseases described to affect humans. Infection with these viruses produces vexing effects to the host, which frequently recur. Infection with herpes simplex viruses is lifelong, and currently there is no vaccine or drug to prevent or cure infection. Prevalence of herpes simplex virus 2 (HSV-2) infection varies significantly depending on the geographical region and nears 20% worldwide. Importantly, HSV-2 is the first cause of genital ulcers in the planet. HSV-2 affects approximately 500 million people around the globe and significantly increases the likelihood of acquiring the human immunodeficiency virus (HIV), as well as its shedding. Thus, controlling HSV-2 infection and spread is of public health concern. Here, we review the diseases produced by herpes simplex viruses, the factors that modulate HSV-2 infection, the relationship between HSV-2 and HIV and novel therapeutic and prophylactic microbicides/antivirals under development to prevent infection and pathological outcomes produced by this virus. We also review mutations associated with HSV-2 resistance to common antivirals.

  9. Varicella zoster virus (VZV) and herpes simplex virus (HSV) in solid organ transplant patients.

    PubMed

    Zuckerman, R A; Limaye, A P

    2013-02-01

    Varicella zoster virus (VZV) and the two herpes simplex viruses (HSV) are human α-herpesviruses that establish life-long latency in neural ganglia after initial primary infection. In the solid organ transplant (SOT) population, manifestations of VZV or HSV may be seen in up to 70% of recipients if no prophylaxis is used, some of them life and organ threatening. While there are effective vaccines to prevent VZV primary infection and reactivation in immunocompetent adults, these vaccines are contraindicated after SOT because they are live-virus vaccines. For HSV, prevention has focused primarily on antiviral strategies because the immunologic correlates of protection and control are different from VZV, making vaccine development more challenging. Current antiviral therapy remains effective for the majority of clinical VZV and HSV infections. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Recombination promoted by DNA viruses: phage λ to herpes simplex virus.

    PubMed

    Weller, Sandra K; Sawitzke, James A

    2014-01-01

    The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage λ and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on λ and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies.

  11. Recombination Promoted by DNA Viruses: Phage λ to Herpes Simplex Virus

    PubMed Central

    Weller, Sandra K.; Sawitzke, James A.

    2015-01-01

    The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage λ and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on λ and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies. PMID:25002096

  12. Electrochemical direct immobilization of DNA sequences for label-free herpes virus detection

    NASA Astrophysics Data System (ADS)

    Tam, Phuong Dinh; Trung, Tran; Tuan, Mai Anh; Chien, Nguyen Duc

    2009-09-01

    DNA sequences/bio-macromolecules of herpes virus (5'-AT CAC CGA CCC GGA GAG GGA C-3') were directly immobilized into polypyrrole matrix by using the cyclic voltammetry method, and grafted onto arrays of interdigitated platinum microelectrodes. The morphology surface of the obtained PPy/DNA of herpes virus composite films was investigated by a FESEM Hitachi-S 4800. Fourier transform infrared spectroscopy (FTIR) was used to characterize the PPy/DNA film and to study the specific interactions that may exist between DNA biomacromolecules and PPy chains. Attempts are made to use these PPy/DNA composite films for label-free herpes virus detection revealed a response time of 60 s in solutions containing as low as 2 nM DNA concentration, and self life of six months when immerged in double distilled water and kept refrigerated.

  13. Effect of Prior Immunization on Induction of Cervical Cancer in Mice by Herpes Simplex Virus Type 2

    NASA Astrophysics Data System (ADS)

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

    1983-12-01

    Previous studies at this laboratory showed that repeated application of inactivated herpes simplex virus type 2 to the mouse cervix produces premalignant and malignant lesions. In the present study mice were inoculated with inactivated herpes simplex virus type 2 or control solution and Freund's adjuvant by intraperitoneal and subcutaneous routes before exposure of the cervix to inactivated virus. It appears that immunization with inactivated virus conferred a protection against the induction of cervical carcinoma.

  14. Primary herpes simplex virus infection mimicking cervical cancer.

    PubMed

    Tomkins, Andrew; White, Catherine; Higgins, Stephen Peter

    2015-06-02

    We report the case of an 18-year-old woman presenting with ulceration of the cervix caused by primary type 2 herpes simplex infection in the absence of skin lesions. The differential diagnosis included cervical cancer and we referred the patient for urgent colposcopy. However, laboratory tests proved the viral aetiology of the cervical ulceration and the cervix had healed completely 3 weeks later. The case highlights the need to consider herpes simplex infection in the differential diagnosis of ulceration of the cervix even when there are no cutaneous signs of herpes.

  15. Imbalanced Oxidative Stress Causes Chlamydial Persistence during Non-Productive Human Herpes Virus Co-Infection

    PubMed Central

    Prusty, Bhupesh K.; Böhme, Linda; Bergmann, Birgit; Siegl, Christine; Krause, Eva; Mehlitz, Adrian; Rudel, Thomas

    2012-01-01

    Both human herpes viruses and Chlamydia are highly prevalent in the human population and are detected together in different human disorders. Here, we demonstrate that co-infection with human herpes virus 6 (HHV6) interferes with the developmental cycle of C. trachomatis and induces persistence. Induction of chlamydial persistence by HHV6 is independent of productive virus infection, but requires the interaction and uptake of the virus by the host cell. On the other hand, viral uptake is strongly promoted under co-infection conditions. Host cell glutathione reductase activity was suppressed by HHV6 causing NADPH accumulation, decreased formation of reduced glutathione and increased oxidative stress. Prevention of oxidative stress restored infectivity of Chlamydia after HHV6-induced persistence. We show that co-infection with Herpes simplex virus 1 or human Cytomegalovirus also induces chlamydial persistence by a similar mechanism suggesting that Chlamydia -human herpes virus co-infections are evolutionary shaped interactions with a thus far unrecognized broad significance. PMID:23077614

  16. LATENT HERPES SIMPLEX VIRUS IN THE CENTRAL NERVOUS SYSTEM OF RABBITS AND MICE

    PubMed Central

    Knotts, F. B.; Cook, M. L.; Stevens, J. G.

    1973-01-01

    Herpes simplex virus (HSV) type 1 induces a long-standing latent infection in the central nervous system of mice and rabbits. The infection was extablished in the brain stems of rabbits after corneal inoculation of the virus, and in the spinal cords of mice after rear footpad infection. In these animals, infectious virus could not be recovered by direct isolation from tissues; it was detected only after the tissues were maintained as organ cultures in vitro. PMID:4353820

  17. New concepts in herpes simplex virus vaccine development: notes from the battlefield

    PubMed Central

    Dasgupta, Gargi; Chentoufi, Aziz A; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

    2009-01-01

    The recent discovery that T cells recognize different sets of herpes simplex virus type 1 and type 2 epitopes from seropositive symptomatic and asymptomatic individuals might lead to a fundamental immunologic advance in vaccine development against herpes infection and diseases. The newly introduced needle-free mucosal (i.e., topical ocular and intravaginal) lipopeptide vaccines provide a novel strategy that might target ocular and genital herpes and possibly provide ‘heterologous protection’ from HIV-1. Indeed, mucosal self-adjuvanting lipopeptide vaccines are easy to manufacture, simple to characterize, extremely pure, cost-effective, highly immunogenic and safe. In this review, we bring together recent published and unpublished data that illuminates the status of epitope-based herpes vaccine development and present an overview of our recent approach to an ‘asymptomatic epitope’-based lipopeptide vaccine. PMID:19627185

  18. Herpes Simplex Virus Sepsis in a Young Woman with Crohn's Disease.

    PubMed

    Haag, Lea-Maxie; Hofmann, Jörg; Kredel, Lea Isabell; Holzem, Christina; Kühl, Anja A; Taube, Eliane T; Schubert, Stefan; Siegmund, Britta; Epple, Hans-Jörg

    2015-12-01

    We present the case of a herpes simplex virus-1 [HSV-1] sepsis with severe herpes hepatitis in a young female treated with triple immunosuppressive therapy [adalimumab, azathioprine, prednisolone] for refractory Crohn's disease [CD]. The patient presented with high fever, generalised abdominal tenderness, strongly elevated transaminases, coagulopathy, and pancytopenia. Comprehensive diagnostics including blood HSV-1 polymerase chain reaction [PCR], liver biopsy, and immunohistochemistry revealed the diagnosis of fulminant herpes hepatitis. HSV-1 positivity of cutaneous lesions proved the disseminated nature of the infection. Early treatment with intravenous acyclovir led to a rapid improvement of the patient's condition and resulted in a full recovery of her liver function. This is the first reported case of HSV-sepsis in a patient with CD. Physicians treating inflammatory bowel disease [IBD] patients with combined immunosuppressive therapy should be aware of the possibility of herpes hepatitis, and early empirical antiviral therapy should be considered in immunosuppressed patients presenting with fever and severe anicteric hepatitis.

  19. Conjunctival Lichen Planus in a Patient With Herpes Simplex Virus Keratitis

    PubMed Central

    Crosby, Michelle B.; Crosby, Christopher V.; Wojno, Ted H.; Grossniklaus, Hans E.

    2010-01-01

    Purpose To report a case of lichen planus in a patient with a history of herpes simplex virus keratitis. Methods Case report. Results A 60-year-old woman with chronic conjunctivitis and a history of herpes simplex virus keratitis was evaluated for irritation and a plaque on her right upper and lower eyelid palpebral conjunctivae. A surgical excision showed acanthosis and an underlying lichenoid infiltrate with a thickened basement membrane. Conclusion Lichen planus of the conjunctiva can be present in the absence of cicatrization in a patient with chronic irritation of the conjunctiva. PMID:19654517

  20. Molecular Characterization of Prostate Cancer Cell Oncolysis by Herpes Simplex Virus ICP0 Mutants

    DTIC Science & Technology

    2005-10-01

    shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number...ahead of print. 15. Chelbi-Alix, M.K. and H. deThe , Herpes virus induced proteasome-dependent degradation of the nuclear bodies-associated PML and SplOO...Biochem 4 143:165-174. 5 9. Chelbi-Alix, M. K., and H. deThe . 1999. Herpes virus induced proteasome-dependent 6 degradation of the nuclear bodies-associated

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

    PubMed

    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.

  2. Study of antiviral and virucidal activities of aqueous extract of Baccharis articulata against Herpes suis virus.

    PubMed

    Torres, Cristina Vanesa; Domínguez, María Julia; Carbonari, José Luis; Sabini, María Carola; Sabini, Liliana Inés; Zanon, Silvia Matilde

    2011-07-01

    Baccharis articulata is native of América and traditionally used for the treatment of digestive disorders and urinary infections. Cytotoxicity of aqueous extracts of B. articulata was investigated in Vero cells. As the maximal non cytotoxic concentration has been established, this concentration has been used to evaluate antiviral and virucidal activities against Herpes suis virus type 1, member of the same subfamily of Herpes simplex virus. Aqueous extracts of B. articulata exhibited more than 95% of virucidal activity. These findings support their potential application as a disinfectant or antiseptic with low toxicity and provide a valuable knowledge to ethnopharmacology properties of Baccharis articulata.

  3. Clinical and neuroimaging findings in neonatal herpes simplex virus infection.

    PubMed

    Bajaj, Monika; Mody, Swati; Natarajan, Girija

    2014-08-01

    In a retrospective review of infants with neonatal herpes simplex virus disease (n=29), we found bilateral multilobar (n=8), pontine (n=3), thalamic (n=6), and internal capsule and corticospinal tract (n=5) involvement on magnetic resonance imaging (MRI). Diffusion-weighted imaging (n=6) performed early revealed additional involvement than detected by conventional MRI. Neurodevelopmental sequelae were correlated with MRI abnormalities. Our findings demonstrate that MRI, including diffusion-weighted imaging, is a valuable prognostic adjunct in neonatal herpes simplex virus disease.

  4. Immunity to herpes simplex virus type 2. Suppression of virus-induced immune responses in ultraviolet B-irradiated mice

    SciTech Connect

    Yasumoto, S.; Hayashi, Y.; Aurelian, L.

    1987-10-15

    Ultraviolet B irradiation (280 to 320 nm) of mice at the site of intradermal infection with herpes simplex virus type 2 increased the severity of the herpes simplex virus type 2 disease and decreased delayed-type hypersensitivity (DTH) responses to viral antigen. Decrease in DTH resulted from the induction of suppressor T cells, as evidenced by the ability of spleen cells from UV-irradiated mice to inhibit DTH and proliferative responses after adoptive transfer. Lymph node cells from UV-irradiated animals did not transfer suppression. DTH was suppressed at the induction but not the expression phase. Suppressor T cells were Lyt-1+, L3T4+, and their activity was antigen-specific. However, after in vitro culture of spleen cells from UV-irradiated mice with herpes simplex virus type 2 antigen, suppressor activity was mediated by Lyt-2+ cells. Culture supernatants contained soluble nonantigen-specific suppressive factors.

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

    PubMed Central

    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

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

    PubMed

    Kennedy, Peter G E; Rovnak, Joel; Badani, Hussain; Cohrs, Randall J

    2015-07-01

    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 increasing

  7. Electron Tomography of Nascent Herpes Simplex Virus Virions▿ †

    PubMed Central

    Baines, Joel D.; Hsieh, Chyong-Ere; Wills, Elizabeth; Mannella, Carmen; Marko, Michael

    2007-01-01

    Cells infected with herpes simplex virus type 1 (HSV-1) were conventionally embedded or freeze substituted after high-pressure freezing and stained with uranyl acetate. Electron tomograms of capsids attached to or undergoing envelopment at the inner nuclear membrane (INM), capsids within cytoplasmic vesicles near the nuclear membrane, and extracellular virions revealed the following phenomena. (i) Nucleocapsids undergoing envelopment at the INM, or B capsids abutting the INM, were connected to thickened patches of the INM by fibers 8 to 19 nm in length and ≤5 nm in width. The fibers contacted both fivefold symmetrical vertices (pentons) and sixfold symmetrical faces (hexons) of the nucleocapsid, although relative to the respective frequencies of these subunits in the capsid, fibers engaged pentons more frequently than hexons. (ii) Fibers of similar dimensions bridged the virion envelope and surface of the nucleocapsid in perinuclear virions. (iii) The tegument of perinuclear virions was considerably less dense than that of extracellular virions; connecting fibers were observed in the former case but not in the latter. (iv) The prominent external spikes emanating from the envelope of extracellular virions were absent from perinuclear virions. (v) The virion envelope of perinuclear virions appeared denser and thicker than that of extracellular virions. (vi) Vesicles near, but apparently distinct from, the nuclear membrane in single sections were derived from extensions of the perinuclear space as seen in the electron tomograms. These observations suggest very different mechanisms of tegumentation and envelopment in extracellular compared with perinuclear virions and are consistent with application of the final tegument to unenveloped nucleocapsids in a compartment(s) distinct from the perinuclear space. PMID:17215293

  8. Oral shedding of herpes simplex virus type 2

    PubMed Central

    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. Methods: Demographic, clinical and laboratory data of patients with documented HSV-2 infection and at least one oral viral culture obtained were selected from the University of Washington Virology Research Clinic database. Results: Of 1388 people meeting the entry criteria, 44 (3.2%) had HSV-2 isolated at least once from their mouths. In comparison with the 1344 people who did not have HSV-2 isolated from their mouth, participants with oral HSV-2 were more likely to be male (OR = 1.9, 95% CI 1.0 to 3.7), HIV positive (OR = 2.9, 95% CI 1.4 to 6.0), and homosexual (OR = 2.2, 95% CI 1.1 to 4.2), and to have collected a larger number of oral specimens (median 32 v 4, p<0.001). Of the 58 days with oral HSV-2 isolation, 15 (25%) occurred during newly acquired HSV-2 infection, 12 (21%) during a recurrence with genital lesions, three (5%) during a recurrence with oral lesions, and three (5%) during a recurrence with oral and genital lesions; 25 (43%) occurred during asymptomatic shedding. Oral HSV-2 was found less frequently than oral HSV-1 (0.06% v 1%, p<0.001) in people with HSV-1 and HSV-2 antibody, and less frequently than genital HSV-2 (0.09% v 7%, p<0.001). Conclusions: Oral reactivation of HSV-2 as defined by viral isolation is uncommon and usually occurs in the setting of first episode of genital HSV-2 or during genital recurrence of HSV-2. PMID:15295123

  9. Detection of herpes viruses in respiratory secretions of patients undergoing artificial ventilation.

    PubMed

    Smith, C A; Conroy, L T; Pollock, M; Ruddy, J; Binning, A; McCruden, E A B

    2010-08-01

    The significance of detection of herpes viruses in respiratory secretions of critically ill patients is controversial. The study aim was to determine the prevalence of herpes virus DNA in respiratory secretions in patients on artificial ventilation. Respiratory secretions taken thrice weekly from 174 patients in a tertiary center intensive therapy unit (ITU) were tested for herpes simplex virus (HSV) by nested PCR. Samples from 61 patients in ITU for 4 days or more were also tested for Epstein Barr Virus (EBV) and cytomegalovirus (CMV) using real-time PCR. HSV positivity increased with ITU stay with 18.6% admission samples positive, 32.5% day 2-5 samples, and 65.9% day 6-39 samples. Being HSV positive on admission did not influence mortality (9/27, 33.3% vs. 38/118, 32.2%) however, subsequently, mortality of those negative but becoming positive was higher than in those remaining negative (10/35, 29% vs. 5/24 21%). At least one sample was EBV positive in 61% and CMV positive in 19% of patients tested. Of 63 patients tested for all three viruses, 4 were positive for three viruses, 23 patients for two viruses, 24 for one virus and 12 were negative for all the above viruses. Detection of HSV, EBV and CMV is common in ITU patients. Becoming HSV positive while in ITU may increase mortality.

  10. The diagnosis of genital herpes – beyond culture: An evidence-based guide for the utilization of polymerase chain reaction and herpes simplex virus type-specific serology

    PubMed Central

    Ratnam, S; Severini, A; Zahariadis, G; Petric, M; Romanowski, B

    2007-01-01

    Accurate identification of persons with genital herpes is necessary for optimal patient management and prevention of transmission. Because of inherent inaccuracies, clinical diagnosis of genital herpes should be confirmed by laboratory testing for the causative agents herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2). Further identification of the HSV type is valuable for counselling on the natural history of infection and risk of transmission. Laboratory methods include antigen detection, culture, polymerase chain reaction (PCR) and conventional and type-specific serology (TSS). PCR has, by far, the greater sensitivity and should be the test of choice for symptomatic cases. HSV-2 TSS is indicated for patients with genital lesions in whom antigen detection, culture or PCR fail to detect HSV, and for patients who are asymptomatic but have a history suggestive of genital herpes. HSV-2 TSS is further indicated for patients infected with HIV. HSV-2 TSS along with HSV-1 TSS may be considered, as appropriate, in evaluating infection and/or immune status in couples discordant for genital herpes, women who develop their first clinical episode of genital herpes during pregnancy, asymptomatic pregnant women whose partners have a history of genital herpes or HIV infection, and women contemplating pregnancy or considering sexual partnership with those with a history of genital herpes. The above should be performed in conjunction with counselling of infected persons and their sex partners. PMID:18923735

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

    SciTech Connect

    Lee, Cheng-Chung; Lin, Li-Ling; Chan, Woan-Eng; Ko, Tzu-Ping; Lai, Jiann-Shiun; Wang, Andrew H.-J.

    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.

  12. Immune responses in mice against herpes simplex virus: mechanisms of protection against facial and ganglionic infections.

    PubMed Central

    Zweerink, H J; Martinez, D; Lynch, R J; Stanton, L W

    1981-01-01

    We performed experiments with mice to determine the nature of the immune response(s) that prevents primary infections of the skin and the trigeminal ganglia with herpes simplex virus. Immunization with infectious herpes simplex virus, inactivated virus, or material enriched for viral glycoproteins protected hairless mice against primary facial and ganglionic infections. Live and inactivated viruses induced neutralizing antibodies, whereas glycoprotein material did not. Instead, glycoprotein material induced antibodies that were largely directed against two glycopolypeptides with molecular weights of 120,000 to 130,000. Hairless mice immunized with glycoprotein material responded faster than control mice in the synthesis of neutralizing antibodies after challenge with infectious virus. Congenital athymic BALB/c (nu/nu) mice were protected against primary facial infections after immunization with glycoprotein material, but glycoprotein-specific antibodies were not induced. Images PMID:6260662

  13. Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment.

    PubMed

    Nason, Martha C; Patel, Eshan U; Kirkpatrick, Allison R; Prodger, Jessica L; Shahabi, Kamnoosh; Tobian, Aaron A R; Gianella, Sara; Kalibbala, Sarah; Ssebbowa, Paschal; Kaul, Rupert; Gray, Ronald H; Quinn, Thomas C; Serwadda, David; Reynolds, Steven J; Redd, Andrew D

    2016-03-01

    Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation.

  14. Prevention of type 2 herpes simplex virus induced cervical carcinoma in mice by prior immunization with a vaccine prepared from type 1 herpes simplex virus.

    PubMed

    Chen, M H; Dong, C Y; Liu, Z H; Skinner, G R; Hartley, C E

    1983-12-01

    Repeated intra-vaginal inoculation of mice with inactivated type 2 herpes simplex virus induced cervical carcinoma in approximately 50% of mice. Prior immunization with subunit vaccine Ac NFU1(S-) BHK reduced the frequency of cervical carcinoma to 19%. Inoculation of mice with a control preparation of uninfected cell extract never induced preinvasive or invasive cervical cancer. There was evidence of an antibody response in every vaccinated and/or innoculated animal. Mice developing cervical cancer had a significantly higher antibody titre to type 2 herpes virus than mice not developing cancer. These results are in general accord with sero-epidemiological studies of preinvasive and invasive cervical carcinoma in human subjects and suggests that this experimental model may be appropriate for further investigation of prevention of human cervical cancer by vaccination.

  15. Relative potencies of different anti-herpes agents in the topical treatment of cutaneous herpes simplex virus infection of athymic nude mice.

    PubMed Central

    Descamps, J; De Clercq, E; Barr, P J; Jones, A S; Walker, R T; Torrence, P F; Shugar, D

    1979-01-01

    Thirteen established anti-herpes compounds have been directly compared in a single assay system for their effects on the development of herpetic skin lesions, and mortality associated therewith, in athymic nude (nu/nu) mice inoculated intracutaneously with herpes simplex virus type 1 (KOS). When applied topically (at 1% in a water-soluble ointment), phosphonoacetic acid, E-5-(2-bromovinyl)-2'-deoxyuridine, acycloguanosine, and trisodium phosphonoformate emerged as the most active agents. PMID:526011

  16. Varicella-Zoster Virus Vasculopathy: The Growing Association Between Herpes Zoster and Strokes.

    PubMed

    Powell, David R; Patel, Shiddhi; Franco-Paredes, Carlos

    2015-09-01

    Varicella-zoster virus (VZV) is herpes virus that after its reactivation from nerve ganglia to cause herpes zoster may lead to a variety of neurologic complications, including encephalitis, meningitis, retinal necrosis or myelitis. In addition, VZV can spread to arteries in the central nervous system and cause hemorrhagic or ischemic complications due to an inflammatory vasculopathy. In fact, there is a growing epidemiological and clinical recognition that there is an association between VZV reactivation and subsequent strokes. Herein, we present a case of an immune compromised individual with reactivation of VZV causing dermatomal herpes zoster followed by multifocal vasculopathy. We also review the literature to highlight key aspects of VZV-associated vasculopathy.

  17. The "Knife-Cut Sign" Revisited: A Distinctive Presentation of Linear Erosive Herpes Simplex Virus Infection in Immunocompromised Patients.

    PubMed

    Cohen, Philip R

    2015-10-01

    The "knife-cut sign" is a distinctive presentation of linear erosive herpes simplex virus infection in immunocompromised patients. To describe a man whose herpes simplex virus infection-related skin lesions demonstrated the "knife-cut sign" and to review the characteristics of reported immunosuppressed individuals with "knife-cut" cutaneous herpes simplex virus lesions. A man with multiple myeloma and post-stem cell transplant cutaneous graft-versus-host disease managed with systemic prednisone and sirolimus developed disseminated cutaneous herpes simplex virus infection with virus-associated linear ulcers of the inguinal folds and the area between his ear and scalp; the lesions at both sites had a distinctive "knife-cut" appearance. Using the PubMed database, an extensive literature search was performed on herpes simplex virus, immunocompromised patient, and "knife-cut sign". Herpes simplex virus infection-associated skin lesions that demonstrate the "knife-cut sign" present in patients who are immunosuppressed secondary to either an underlying medical condition or a systemic therapy or both. The distinctive virus-related cutaneous lesions appear as linear ulcers and fissures in intertriginous areas, such as the folds in the inguinal area, the vulva, and the abdomen; in addition, other sites include beneath the breast, within the gluteal cleft, and the area between the ear and the scalp. Not only herpes simplex virus-2, but also herpes simplex virus-1 has been observed as the causative viral serotype; indeed, herpes simplex virus-1 has been associated with genital and inframammary lesions in addition to those above the neck. Direct fluorescent antibody testing is a rapid method for confirming the clinically suspected viral infection; however, since false-negative direct fluorescent antibody testing occurred in some of the patients, it may be prudent to also perform viral cultures and possibly lesional skin biopsies to establish the diagnosis. The herpes simplex

  18. Different presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii in schizophrenia: meta-analysis and analytical study

    PubMed Central

    Gutiérrez-Fernández, José; Luna del Castillo, Juan de Dios; Mañanes-González, Sara; Carrillo-Ávila, José Antonio; Gutiérrez, Blanca; Cervilla, Jorge A; Sorlózano-Puerto, Antonio

    2015-01-01

    In the present study we have performed both a meta-analysis and an analytical study exploring the presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii antibodies in a sample of 143 schizophrenic patients and 143 control subjects. The meta-analysis was performed on papers published up to April 2014. The presence of serum immunoglobulin G and immunoglobulin A was performed by enzyme-linked immunosorbent assay test. The detection of microbial DNA in total peripheral blood was performed by nested polymerase chain reaction. The meta-analysis showed that: 1) C. pneumoniae DNA in blood and brain are more common in schizophrenic patients; 2) there is association with parasitism by T. gondii, despite the existence of publication bias; and 3) herpes viruses were not more common in schizophrenic patients. In our sample only anti-Toxoplasma immunoglobulin G was more prevalent and may be a risk factor related to schizophrenia, with potential value for prevention. PMID:25848282

  19. Different presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii in schizophrenia: meta-analysis and analytical study.

    PubMed

    Gutiérrez-Fernández, José; Luna Del Castillo, Juan de Dios; Mañanes-González, Sara; Carrillo-Ávila, José Antonio; Gutiérrez, Blanca; Cervilla, Jorge A; Sorlózano-Puerto, Antonio

    2015-01-01

    In the present study we have performed both a meta-analysis and an analytical study exploring the presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii antibodies in a sample of 143 schizophrenic patients and 143 control subjects. The meta-analysis was performed on papers published up to April 2014. The presence of serum immunoglobulin G and immunoglobulin A was performed by enzyme-linked immunosorbent assay test. The detection of microbial DNA in total peripheral blood was performed by nested polymerase chain reaction. The meta-analysis showed that: 1) C. pneumoniae DNA in blood and brain are more common in schizophrenic patients; 2) there is association with parasitism by T. gondii, despite the existence of publication bias; and 3) herpes viruses were not more common in schizophrenic patients. In our sample only anti-Toxoplasma immunoglobulin G was more prevalent and may be a risk factor related to schizophrenia, with potential value for prevention.

  20. Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment.

    PubMed

    Díaz Betancourt, María Lilia; Klínger Hernández, Julio César; Niño Castaño, Victoria Eugenia

    2012-10-01

    Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings' health.

  1. Attitudes and Willingness to Assume Risk of Experimental Therapy to Eradicate Genital Herpes Simplex Virus Infection.

    PubMed

    Oseso, Linda; Magaret, Amalia S; Jerome, Keith R; Fox, Julie; Wald, Anna

    2016-09-01

    Current treatment of genital herpes is focused on ameliorating signs and symptoms but is not curative. However, as potential herpes simplex virus (HSV) cure approaches are tested in the laboratory, we aimed to assess the interest in such studies by persons with genital herpes and the willingness to assume risks associated with experimental therapy. We constructed an anonymous online questionnaire that was posted on websites that provide information regarding genital herpes. The questions collected demographic and clinical information on adults who self-reported as having genital herpes, and assessed attitudes toward and willingness to participate in HSV cure clinical research. Seven hundred eleven participants provided sufficient responses to be included in the analysis. Sixty-six percent were women; the median age was 37 years, and the median time since genital HSV diagnosis was 4.7 years. The willingness to participate in trials increased from 59.0% in phase 1 to 68.5% in phase 2, and 81.2% in phase 3 trials, and 40% reported willingness to participate even in the absence of immediate, personal benefits. The most desirable outcome was the elimination of risk for transmission to sex partner or neonate. The mean perceived severity of receiving a diagnosis of genital HSV-2 was 4.2 on a scale of 1 to 5. Despite suppressive therapy available, persons with genital herpes are interested in participating in clinical research aimed at curing HSV, especially in more advanced stages of development.

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

    PubMed

    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.

  3. Behaviour of IgG antibody avidity for the antigen and of IgA antibody in active cytomegalovirus, Epstein-Barr virus, herpes simplex virus and human herpes virus 6 infections. Adaptation of a commercial test.

    PubMed

    Gutiérrez, J; Rodríguez, M; Maroto, M C; Piédrola, G; Peirón, J

    1997-07-01

    The clinical value of specific IgA and IgG antibody avidity to herpes simplex virus, cytomegalovirus, Epstein-Barr virus and human herpes virus 6 for the detection of active disease and primary infection, respectively, was evaluated. The IgG avidity test, with a break point of 55%, for the detection of primary infection, and of the IgA test for the detection of disease, were associated with a sensitivity of 97% and 64%, respectively; specificity of 100% and 82%; a positive predictive value of 100% and 76%; and a negative predictive value of 96% and 72%, respectively.

  4. [Seroepidemiological study of Herpes simplex virus type 2 in adult women of Costa Rica].

    PubMed

    Jimémez, J M; Fuentes, L G; Cordero, C; Alfaro, G

    1979-12-01

    The frequency of genital Herpes simplex type 2 infections in a group of twenty adult Costa Rican women was studied by isolation of the virus and the measurement of neutralizing antibody activity in sera. The virus could not be isolated in any of the vaginal secretions. Neutralizing antibody activity to herpes virus types 1 and 2 was found in sera from sixteen subjects. An antibody II/I index equal to or larger than 87, indicative of infection with Herpes simplex type 2 was found in fifty per cent of the population studied, a second segment was composed by the subjects with indices below 87. Evaluation of antibody activity to Herpes simplex type 2 revealed that: a) only a small percentage of the women lacked detectable antibody activity to the virus; b) there is a significant difference (p < 0.005) between the mean number of years of sexual experience among the two population segments; and c) there is a positive correlation (p < 0.05) between II/I index values and age among the women of the population segment with a II/I index equal to or larger than 87.

  5. Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea.

    PubMed

    Polcicova, Katarina; Biswas, Partha Sarathi; Banerjee, Kaustuv; Wisner, Todd W; Rouse, Barry T; Johnson, David C

    2005-08-09

    Herpes stromal keratitis is an immunopathologic disease in the corneal stroma leading to scarring, opacity, and blindness, and it is an important problem in common corneal surgeries. Paradoxically, virus antigens are largely focused in the epithelial layer of the cornea and not in the stromal layer, and viral antigens are eliminated before stromal inflammation develops. It is not clear what drives inflammation, whether viral antigens are necessary, or how viral antigens reach the stroma. It has been proposed that herpes simplex virus (HSV) travels from the corneal epithelium to sensory ganglia then returns to the stroma to cause disease. However, there is also evidence of HSV DNA and infectious virus persistent in corneas, and HSV can be transmitted to transplant recipients. To determine whether HSV resident in the cornea could cause herpes stromal keratitis, we constructed an HSV US9- mutant that had diminished capacity to move in neuronal axons. US9- HSV replicated and spread normally in the mouse corneal epithelium and to the trigeminal ganglia. However, US9- HSV was unable to return from ganglia to the cornea and failed to cause periocular skin disease, which requires zosteriform spread from neurons. Nevertheless, US9- HSV caused keratitis. Therefore, herpes keratitis can occur without anterograde transport from ganglia to the cornea, probably mediated by virus persistent in the cornea.

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

    ERIC Educational Resources Information Center

    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:…

  7. Antiviral Activity of Crude Hydroethanolic Extract from Schinus terebinthifolia against Herpes simplex Virus Type 1.

    PubMed

    Nocchi, Samara Requena; Companhoni, Mychelle Vianna Pereira; de Mello, João Carlos Palazzo; Dias Filho, Benedito Prado; Nakamura, Celso Vataru; Carollo, Carlos Alexandre; Silva, Denise Brentan; Ueda-Nakamura, Tânia

    2017-04-01

    Herpes simplex virus infections persist throughout the lifetime of the host and affect more than 80 % of the humans worldwide. The intensive use of available therapeutic drugs has led to undesirable effects, such as drug-resistant strains, prompting the search for new antiherpetic agents. Although diverse bioactivities have been identified in Schinus terebinthifolia, its antiviral activity has not attracted much attention. The present study evaluated the antiherpetic effects of a crude hydroethanolic extract from the stem bark of S. terebinthifolia against Herpes simplex virus type 1 in vitro and in vivo as well as its genotoxicity in bone marrow in mammals and established the chemical composition of the crude hydroethanolic extract based on liquid chromatography-diode array detector-mass spectrometry and MS/MS. The crude hydroethanolic extract inhibited all of the tested Herpes simplex virus type 1 strains in vitro and was effective in the attachment and penetration stages, and showed virucidal activity, which was confirmed by transmission electron microscopy. The micronucleus test showed that the crude hydroethanolic extract had no genotoxic effect at the concentrations tested. The crude hydroethanolic extract afforded protection against lesions that were caused by Herpes simplex virus type 1 in vivo. Liquid chromatography-diode array detector-mass spectrometry and MS/MS identified 25 substances, which are condensed tannins mainly produced by a B-type linkage and prodelphinidin and procyanidin units. Georg Thieme Verlag KG Stuttgart · New York.

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

    ERIC Educational Resources Information Center

    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:…

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

    USDA-ARS?s Scientific Manuscript database

    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...

  10. Amino-terminal sequence of glycoprotein D of herpes simplex virus types 1 and 2

    SciTech Connect

    Eisenberg, R.J.; Long, D.; Hogue-Angeletti, R.; Cohen, G.H.

    1984-01-01

    Glycoprotein D (gD) of herpes simplex virus is a structural component of the virion envelope which stimulates production of high titers of herpes simplex virus type-common neutralizing antibody. The authors caried out automated N-terminal amino acid sequencing studies on radiolabeled preparations of gD-1 (gD of herpes simplex virus type 1) and gD-2 (gD of herpes simplex virus type 2). Although some differences were noted, particularly in the methionine and alanine profiles for gD-1 and gD-2, the amino acid sequence of a number of the first 30 residues of the amino terminus of gD-1 and gD-2 appears to be quite similar. For both proteins, the first residue is a lysine. When we compared out sequence data for gD-1 with those predicted by nucleic acid sequencing, the two sequences could be aligned (with one exception) starting at residue 26 (lysine) of the predicted sequence. Thus, the first 25 amino acids of the predicted sequence are absent from the polypeptides isolated from infected cells.

  11. Pediatric Herpes Simplex Virus Encephalitis Complicated by N-Methyl-D-aspartate Receptor Antibody Encephalitis.

    PubMed

    Bamford, Alasdair; Crowe, Belinda H A; Hacohen, Yael; Lin, Jean-Pierre; Clarke, Antonia; Tudor-Williams, Gareth; Sancho-Shimizu, Vanessa; Vincent, Angela; Lim, Ming; Pullaperuma, Sunil P

    2015-06-01

    N-methyl-D-aspartate receptor antibodies (NMDAR-Abs) can contribute to neurological relapse after herpes simplex virus encephalitis (HSE). We describe a child with NMDAR-Ab encephalitis after HSE, which was recognized and treated early. We discuss the case in the context of existing reports, and we propose a modified immunotherapy strategy to minimize risk of viral reactivation.

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

    PubMed

    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.

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

    SciTech Connect

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Isolation of B virus (herpes group) from the central nervous system of a rhesus monkey.

    PubMed

    MELNICK, J L; BANKER, D D

    1954-08-01

    While passaging a recently isolated strain of poliomyelitis virus through a rhesus monkey, another virus was procured from its central nervous system. After intracerebral inoculation, the virus produced meningoencephalitis in monkeys, cotton rats, hamsters, guinea pigs, and rabbits; after intracutaneous inoculation a necrotic skin lesion was produced in the monkey and rabbit and this was often followed by myelitis. The virus could also be passed in newborn mice less than 48 hours old and in chick embryos by inoculation of the chorioallantoic membrane. Immunological and host range studies revealed this virus to be related to the B virus originally described by Sabin and Wright in 1934 (1). To our knowledge this is the first record of B virus having been isolated from a monkey, and lends support to the inclusion of this agent as the simian member of the herpes group. The infection is not uncommon in monkey stocks, as revealed by the finding of antibodies to the virus in their sera. In the present series 9 of 44 monkeys gave positive antibody tests. Gamma globulin prepared in the United States in 1945, 1951, and 1953, as well as a certain proportion of sera from normal individuals in Bombay, India, and elsewhere, showed neutralizing activity against the new strain of B virus, and also to herpes simplex virus. This may be the result of the partial crossing which exists between the two viruses.

  16. ISOLATION OF B VIRUS (HERPES GROUP) FROM THE CENTRAL NERVOUS SYSTEM OF A RHESUS MONKEY

    PubMed Central

    Melnick, Joseph L.; Banker, Dushyant D.

    1954-01-01

    While passaging a recently isolated strain of poliomyelitis virus through a rhesus monkey, another virus was procured from its central nervous system. After intracerebral inoculation, the virus produced meningoencephalitis in monkeys, cotton rats, hamsters, guinea pigs, and rabbits; after intracutaneous inoculation a necrotic skin lesion was produced in the monkey and rabbit and this was often followed by myelitis. The virus could also be passed in newborn mice less than 48 hours old and in chick embryos by inoculation of the chorioallantoic membrane. Immunological and host range studies revealed this virus to be related to the B virus originally described by Sabin and Wright in 1934 (1). To our knowledge this is the first record of B virus having been isolated from a monkey, and lends support to the inclusion of this agent as the simian member of the herpes group. The infection is not uncommon in monkey stocks, as revealed by the finding of antibodies to the virus in their sera. In the present series 9 of 44 monkeys gave positive antibody tests. Gamma globulin prepared in the United States in 1945, 1951, and 1953, as well as a certain proportion of sera from normal individuals in Bombay, India, and elsewhere, showed neutralizing activity against the new strain of B virus, and also to herpes simplex virus. This may be the result of the partial crossing which exists between the two viruses. PMID:13286422

  17. Case report: epithelial intracytoplasmic herpes viral inclusions associated with an outbreak of duck virus enteritis

    USGS Publications Warehouse

    Barr, B.C.; Jessup, David A.; Docherty, Douglas E.; Lownestine, L.J.

    1992-01-01

    Several muscovy ducks from a free-roaming flock of 65 muscovy and mallard ducks died over a 3-week period. Three muscovy ducks were necropsied. Gross and microscopic changes were compatible with duck virus enteritis, and the virus was isolated. In addition to intranuclear viral inclusion bodies in several tissues, intracytoplasmic inclusion bodies were present in esophageal and cloacal epithelium, By electron microscopy, the membrane-bound intracytoplasmic inclusions were found to contain enveloped herpesvirus, and nuclei contained herpes viral nucleocapsids.

  18. Effect of Acyclovir on Viral Protein Synthesis in Cells Infected with Herpes Simplex Virus Type 1

    PubMed Central

    Furman, Phillip A.; McGuirt, Paul V.

    1983-01-01

    The effect of the antiviral agent 9-(2-hydroxyethoxymethyl)guanine (acyclovir) on herpes simplex virus type 1 protein synthesis during virus replication was examined. Treatment of infected cells with acyclovir markedly affected the amounts of the four major glycosylated and certain non-glycosylated viral polypeptides synthesized; other viral polypeptides were made in normal amounts. The reduced amount of late protein synthesis was most likely due to the inhibition of progeny viral DNA synthesis by acyclovir. Images PMID:6301368

  19. [Presence of autocomplementary RNA with viral specificity in cells infected with herpes virus].

    PubMed

    Béchet, J M; Montagnier, L; Latarjet, R

    1975-01-13

    RNA from cells infected with Herpes simplex virus contain a higher percentage of double-stranded RNA than non-infected cells. This percentage increases three-fold upon self-annealing. The complementary RNA sequences were shown to be virus-specific by the following criteria: (1) high melting temperature than double-stranded RNA from non infected cells; (2) higher density in caesium sulphate; (3) specific hybridization with viral DNA.

  20. The influence of the milieu on the rate of neutralisation of herpes simplex virus 1.

    PubMed

    Bolt, C E; Davies, J A; Randall, S; Skinner, G R

    1998-01-01

    The rate of neutralisation of herpes simplex virus 1 was increased by up to more than five hundred-fold when the virus suspension and antiserum were each diluted to one hundred-fold in water instead of phosphate buffered saline. This phenomenon, which was observed for two human positive sera and a rabbit purified polyclonal antibody, may represent an unrecognised homeostatic mechanism where neutralising antibody is 'dilution-fast' under physiological conditions of transudation or pathological conditions of inflammation.

  1. Pregnancy and herpes

    MedlinePlus

    ... sharing features on this page, please enable JavaScript. Newborn infants can become infected with herpes virus during pregnancy, during labor or delivery, or after birth. Causes Newborn infants can become infected with herpes virus: In the ...

  2. Structures of herpes simplex virus type 1 genes required for replication of virus DNA.

    PubMed Central

    McGeoch, D J; Dalrymple, M A; Dolan, A; McNab, D; Perry, L J; Taylor, P; Challberg, M D

    1988-01-01

    Recently, a method has been developed to identify regions in the genome of herpes simplex virus type 1 (HSV-1) which contain genes required for DNA synthesis from an HSV-1 origin of DNA replication, and seven genomic loci have been identified as representing the necessary and sufficient gene set for such replication (C. A. Wu, N. J. Nelson, D. J. McGeoch, and M. D. Challberg, J. Virol. 62:435-443, 1988). Two of the loci represent the well-known genes for DNA polymerase and major DNA-binding protein, but the remainder had little or no previous characterization. In this report we present the DNA sequences of the five newly identified genes and their deduced transcript organizations and encoded amino acid sequences. These genes were designated UL5, UL8, UL9, UL42, and UL52 and were predicted to encode proteins with molecular weights of, respectively, 99,000, 80,000, 94,000, 51,000, and 114,000. All of these genes had clear counterparts in the genome of the related alphaherpesvirus varicella-zoster virus, but only UL5 and UL52 were detectably conserved in the distantly related gammaherpesvirus Epstein-Barr virus, as judged by amino acid sequence similarity. The sequence of the UL5 protein, and of its counterparts in the other viruses, contained a region closely resembling known ATP-binding sites; this could be indicative, for instance, of a helicase or primase activity. PMID:2826807

  3. CD11c controls herpes simplex virus 1 responses to limit virus replication during primary infection.

    PubMed

    Allen, Sariah J; Mott, Kevin R; Chentoufi, Aziz A; BenMohamed, Lbachir; Wechsler, Steven L; Ballantyne, Christie M; Ghiasi, Homayon

    2011-10-01

    CD11c is expressed on the surface of dendritic cells (DCs) and is one of the main markers for identification of DCs. DCs are the effectors of central innate immune responses, but they also affect acquired immune responses to infection. However, how DCs influence the efficacy of adaptive immunity is poorly understood. Here, we show that CD11c(+) DCs negatively orchestrate both adaptive and innate immunity against herpes simplex virus type 1 (HSV-1) ocular infection. The effectiveness and quantity of virus-specific CD8(+) T cell responses are increased in CD11c-deficient animals. In addition, the levels of CD83, CD11b, alpha interferon (IFN-α), and IFN-β, but not IFN-γ, were significantly increased in CD11c-deficient animals. Higher levels of IFN-α, IFN-β, and CD8(+) T cells in the CD11c-deficient mice may have contributed to lower virus replication in the eye and trigeminal ganglia (TG) during the early period of infection than in wild-type mice. However, the absence of CD11c did not influence survival, severity of eye disease, or latency. Our studies provide for the first time evidence that CD11c expression may abrogate the ability to reduce primary virus replication in the eye and TG via higher activities of type 1 interferon and CD8(+) T cell responses.

  4. Construction of Poxviruses as Cloning Vectors: Insertion of the Thymidine Kinase Gene from Herpes Simplex Virus into the DNA of Infectious Vaccinia Virus

    NASA Astrophysics Data System (ADS)

    Panicali, Dennis; Paoletti, Enzo

    1982-08-01

    We have constructed recombinant vaccinia viruses containing the thymidine kinase gene from herpes simplex virus. The gene was inserted into the genome of a variant of vaccinia virus that had undergone spontaneous deletion as well as into the 120-megadalton genome of the large prototypic vaccinia variant. This was accomplished via in vivo recombination by contransfection of eukaryotic tissue culture cells with cloned BamHI-digested thymidine kinase gene from herpes simplex virus containing flanking vaccinia virus DNA sequences and infectious rescuing vaccinia virus. Pure populations of the recombinant viruses were obtained by replica filter techniques or by growth of the recombinant virus in biochemically selective medium. The herpes simplex virus thymidine kinase gene, as an insert in vaccinia virus, is transcribed in vivo and in vitro, and the fidelity of in vivo transcription into a functional gene product was detected by the phosphorylation of 5-[125I]iodo-2'-deoxycytidine.

  5. Antibody activity to type 1 and type 2 herpes simplex virus in human cervical mucus.

    PubMed

    Coughlan, B M; Skinner, G R

    1977-08-01

    Neutralizing antibody activity in cervical mucus to type 1 herpes virus was detected in 24 of 28 patients, and to type 2 herpes simplex virus in 18 of 24 patients. The neutralizing antibody activity resisted heat inactivation for 30 minutes at 56 degrees C, was independent of complement and followed first order kinetics. There was evidence of antibody against both virus types in immunoglobulin fractions IgG and IgA, the latter containing approximately threefold greater neutralizing antibody activity per unit of immunoglobulin concentration. Type 1 and type 2 neutralizing antibody activity showed a positive but weak correlation and type 2 neutralizing antibody activity showed a positive but weak correlation and a type-common immunoprecipitin was identified in all concentrated pooled mucus samples. However, type-specific neutralizing antibody against both virus types was identified in pooled mucus samples by heterologous absorption techniques. There was a relatively higher average type 2 neutralizing antibody activity in the mucus than in the serum and there was no correlation between serum and mucus antibody levels for either virus type. These observations support the concept of an independent local antibody system for herpes simplex virus in the uterine cervix.

  6. Serological relatedness of herpes simplex viruses. Type-specificity of antibody response.

    PubMed Central

    Skinner, G R; Thouless, M E; Trueman, S; Edwards, J; Gibbs, A J

    1976-01-01

    The serological relatedness of forty-seven strains of type 1 and type 2 herpes simplex virus was investigated by reciprocal and non-reciprocal neutralization kinetics. Early rabbit antisera divided the virus strains into two distinct groups where confident indentification of virus type was possible. Hyperimmune mouse and rabbit antisera did not divide the two virus types into two distinct non-over-lapping groups. The extent of overlap varied with the particular attribute of the virus being studied. The virus types were best discriminated by their neutralizability by type 1 antisera and least well by their neutralizability by type 2 antisera. The results of reciprocal kinetic neutralization test with hyperimmune mouse antisera were analysed by multi-dimensional cluster analysis. Hyperimmune mouse or rabbit antisera could not be discriminated with respect to their immunogenic type by their absolute neutralization rate constants against either type 1 or type 2 virus, but could be distinguished on a group basis by their relative neutralizability against both virus types (antiserum specificity attribute); however, using this latter criterion, the type of immunogen could only be predicted in seven of the forty antisera under test. 'Early' mouse antisera could also be distinguished as groups by their absolute k-values against type 1 herpes virus. Thus, immunogenic identification, on other than a group basis, was unreliable. The specificity of a given serum was inversely related to its titre. There was a positive correlation between the specificity of a given virus strain and of its corresponding antiserum. PMID:194831

  7. Serological relatedness of herpes simplex viruses. Type-specificity of antibody response.

    PubMed

    Skinner, G R; Thouless, M E; Trueman, S; Edwards, J; Gibbs, A J

    1976-09-01

    The serological relatedness of forty-seven strains of type 1 and type 2 herpes simplex virus was investigated by reciprocal and non-reciprocal neutralization kinetics. Early rabbit antisera divided the virus strains into two distinct groups where confident indentification of virus type was possible. Hyperimmune mouse and rabbit antisera did not divide the two virus types into two distinct non-over-lapping groups. The extent of overlap varied with the particular attribute of the virus being studied. The virus types were best discriminated by their neutralizability by type 1 antisera and least well by their neutralizability by type 2 antisera. The results of reciprocal kinetic neutralization test with hyperimmune mouse antisera were analysed by multi-dimensional cluster analysis. Hyperimmune mouse or rabbit antisera could not be discriminated with respect to their immunogenic type by their absolute neutralization rate constants against either type 1 or type 2 virus, but could be distinguished on a group basis by their relative neutralizability against both virus types (antiserum specificity attribute); however, using this latter criterion, the type of immunogen could only be predicted in seven of the forty antisera under test. 'Early' mouse antisera could also be distinguished as groups by their absolute k-values against type 1 herpes virus. Thus, immunogenic identification, on other than a group basis, was unreliable. The specificity of a given serum was inversely related to its titre. There was a positive correlation between the specificity of a given virus strain and of its corresponding antiserum.

  8. Herpes simplex virus 2 infection in women attending an antenatal clinic in Fuzhou, China

    PubMed Central

    Chen, Xiang‐Sheng; Yin, Yue‐Ping; Chen, Lei‐Ping; Yu, Yan‐Hua; Wei, Wan‐Hui; Thuy, Nguyen Thi Thanh; Smith, Jennifer S

    2007-01-01

    Genital herpes caused by herpes simplex virus (HSV) infection is one of the most prevalent sexually transmitted infections (STIs) and the most common cause of genital ulcer disease (GUD) in developed and developing countries. The monitoring of HSV‐2 seroprevalence in pregnant women can identify women at a higher risk of HIV and of neonatal HSV transmission. Very few data are available on type specific seroprevalence of HSV‐2 in China, with only one previous study from southern China. Consequently, we conducted a survey to determine type specific seroprevalence of HSV‐2 and associated risk factors in Fuzhou City, eastern China. PMID:17475682

  9. Herpes simplex virus 2 infection in women attending an antenatal clinic in Fuzhou, China.

    PubMed

    Chen, Xiang-Sheng; Yin, Yue-Ping; Chen, Lei-Ping; Yu, Yan-Hua; Wei, Wan-Hui; Thuy, Nguyen Thi Thanh; Smith, Jennifer S

    2007-08-01

    Genital herpes caused by herpes simplex virus (HSV) infection is one of the most prevalent sexually transmitted infections (STIs) and the most common cause of genital ulcer disease (GUD) in developed and developing countries. The monitoring of HSV-2 seroprevalence in pregnant women can identify women at a higher risk of HIV and of neonatal HSV transmission. Very few data are available on type specific seroprevalence of HSV-2 in China, with only one previous study from southern China. Consequently, we conducted a survey to determine type specific seroprevalence of HSV-2 and associated risk factors in Fuzhou City, eastern China.

  10. Reduced tumorigenicity of rodent tumour cells and tumour explants following infection with wild type and mutant herpes simplex virus, bovine mammillitis virus and encephalomyocarditis virus.

    PubMed Central

    Skinner, G. R.; Cowan, M.; Davies, J.; Brookes, K.; Billstrom, M.; Buchan, A.

    1988-01-01

    The tumorigenicity of neoplastic hamster and mouse cell lines and tumour explants was reduced by infection with herpes simplex virus (HSV-1), a thymidine-kinaseless mutant of herpes simplex virus, namely 'MDK', encephalomyocarditis virus (EMC) and bovine mammillitis virus (BMV). There was an approximate relationship between duration of virus infection in vitro and reduction in incidence and/or rate of tumour development. The rate of tumour development was also reduced by 'site inoculation' of virus (HSV-1) at various time intervals following inoculation of tumorigenic BHK 21 cells indicating that virus was capable of reducing the rate of tumour development in a situation where the neoplastic cells were already transplanted into the susceptible host species. It is suggested that the therapeutic role of wild type, mutant or recombinant viruses merits further exploration towards prevention and treatment of human cancer. PMID:2846027

  11. Reduced tumorigenicity of rodent tumour cells and tumour explants following infection with wild type and mutant herpes simplex virus, bovine mammillitis virus and encephalomyocarditis virus.

    PubMed

    Skinner, G R; Cowan, M; Davies, J; Brookes, K; Billstrom, M; Buchan, A

    1988-08-01

    The tumorigenicity of neoplastic hamster and mouse cell lines and tumour explants was reduced by infection with herpes simplex virus (HSV-1), a thymidine-kinaseless mutant of herpes simplex virus, namely 'MDK', encephalomyocarditis virus (EMC) and bovine mammillitis virus (BMV). There was an approximate relationship between duration of virus infection in vitro and reduction in incidence and/or rate of tumour development. The rate of tumour development was also reduced by 'site inoculation' of virus (HSV-1) at various time intervals following inoculation of tumorigenic BHK 21 cells indicating that virus was capable of reducing the rate of tumour development in a situation where the neoplastic cells were already transplanted into the susceptible host species. It is suggested that the therapeutic role of wild type, mutant or recombinant viruses merits further exploration towards prevention and treatment of human cancer.

  12. Fluorescent tagging of herpes simplex virus tegument protein VP13/14 in virus infection.

    PubMed

    Donnelly, M; Elliott, G

    2001-03-01

    The cellular site of herpesvirus tegument assembly has yet to be defined. We have previously used a recombinant herpes simplex virus type 1 expressing a green fluorescent protein (GFP)-tagged tegument protein, namely VP22, to show that VP22 is localized exclusively to the cytoplasm during infection. Here we have constructed a similar virus expressing another fluorescent tegument protein, YFP-VP13/14, and have visualized the intracellular localization of this second tegument protein in live infected cells. In contrast to VP22, VP13/14 is targeted predominantly to the nuclei of infected cells at both early and late times in infection. More specifically, YFP-13/14 localizes initially to the nuclear replication compartments and then progresses into intense punctate domains that appear at around 12 h postinfection. At even later times this intranuclear punctate fluorescence is gradually replaced by perinuclear micropunctate and membranous fluorescence. While the vast majority of YFP-13/14 seems to be targeted to the nucleus, a minor subpopulation also appears in a vesicular pattern in the cytoplasm that closely resembles the pattern previously observed for GFP-22. Moreover, at late times weak fluorescence appears at the cell periphery and in extracellular virus particles, confirming that YFP-13/14 is assembled into virions. This predominantly nuclear targeting of YFP-13/14 together with the cytoplasmic targeting of VP22 may imply that there are multiple sites of tegument protein incorporation along the virus maturation pathway. Thus, our YFP-13/14-expressing virus has revealed the complexity of the intracellular targeting of VP13/14 and provides a novel insight into the mechanism of tegument, and hence virus, assembly.

  13. Assessment of skin test with varicella-zoster virus antigen for predicting the risk of herpes zoster.

    PubMed

    Okuno, Y; Takao, Y; Miyazaki, Y; Ohnishi, F; Okeda, M; Yano, S; Kumihashi, H; Gomi, Y; Maeda, K; Ishikawa, T; Mori, Y; Asada, H; Iso, H; Yamanishi, K

    2013-04-01

    The Shozu Herpes Zoster (SHEZ) Study was designed to clarify the incidence of and predictive and immunological factors for herpes zoster in a defined community-based Japanese population. As part of this series, a total of 5683 residents aged ≥50 years received a varicella-zoster virus (VZV) skin test with VZV antigen, and 48 h later, the erythema and oedema were assessed by measuring the longest diameter. The diameters of both the erythema and oedema decreased with the increasing age of the subject. Sixty-three subjects contracted herpes zoster within a year after receiving the VZV skin test. Analysis of the herpes zoster incidence rate vs. the skin test reaction revealed that the shorter the diameter of erythema or oedema, the greater the likelihood of herpes zoster. These results demonstrated that the VZV skin test is an excellent surrogate marker for predicting the risk of herpes zoster.

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

    PubMed

    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.

  15. Herpes simplex virus infection in a university health population: clinical manifestations, epidemiology, and implications.

    PubMed

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

    2010-01-01

    The authors described clinical presentations of oral and genital herpes simplex virus (HSV) infections in a university health population and implications of these findings. Using a standardized data collection tool, 215 records of patients with symptomatic culture-positive HSV infections were reviewed. HSV-1 accounted for 78% of female and 85% of male genital herpes (GH) infections, and oral herpes (OH) infections presented as an acute febrile illness (AFI) in 51% of those 18 to 24 years old. HSV-2 accounted for 68% of GH infections among adults 25 or older. As seroprevalence for both HSV-1 and HSV-2 in the United States is decreasing, a growing college age cohort is at risk for primary HSV-1 infection. The proportion of GH caused by HSV-1 also continues to increase. This understanding has implications for clinical care, sexual health programming, and counseling strategies.

  16. The Type I Interferon Response and Age-Dependent Susceptibility to Herpes Simplex Virus Infection.

    PubMed

    Giraldo, Daniel; Wilcox, Douglas R; Longnecker, Richard

    2017-05-01

    Herpes simplex virus type 1 (HSV-1) is a highly prevalent human neurotropic pathogen. HSV-1 infection is associated with a variety of diseases ranging from benign orolabial lesions to more serious and even life-threatening conditions such as herpes simplex keratitis and herpes simplex encephalitis (HSE). HSE is a rare occurrence among healthy adult individuals, but newborns are a particularly susceptible population. Type I IFN signaling has been identified as a crucial component of the innate immune response to the control of HSV-1 infection. In this study, we review the contribution of the type I IFN response to controlling HSV-1 infection, and differences in the early host response between adults and newborns that may contribute to the increased susceptibility to infection and central nervous system disease in newborns.

  17. A nurse practitioner's guide to the management of herpes simplex virus-1 in children.

    PubMed

    Drugge, Janel M; Allen, Patricia Jackson

    2008-01-01

    This state of the science clinical article focuses on ways pediatric clinicians can manage herpes simplex virus-1 (HSV-1) infections in children and adolescents. HSV-1 infections can be transmitted during close contact with asymptomatic and symptomatic individuals (Waggoner-Fountain & Grossman, 2004). Recurrent HSV-1 outbreaks are believed to be caused by various endogenous and exogenous triggers. These HSV-1 outbreaks cause physical and emotional consequences in children and their families. HSV-1 infections in children most commonly cause gingivostomatitis, but these infections can also cause various skin infections, including herpetic whitlow, herpes gladiatorum, eczema herpeticum, and herpes genitalis. It is critical for pediatric clinicians to be familiar with the pathophysiology and clinical manifestations in order to effectively identify, manage, and treat HSV-1 infections with a variety of topical or systemic medications, as well as with prevention strategies and nutritional supplementations.

  18. Physical and functional domains of the herpes simplex virus transcriptional regulatory protein ICP4.

    PubMed Central

    DeLuca, N A; Schaffer, P A

    1988-01-01

    A characteristic common to DNA animal viruses is the expression early in infection of viral proteins that act in trans to regulate subsequent RNA polymerase II-dependent transcription of the remainder of the viral genome. The predominant transcriptional regulatory protein specified by herpes simplex virus type 1 is the immediate-early protein ICP4. ICP4 is a complex multifunctional protein required for the activation of many herpes simplex virus type 1 transcriptional units and for repression of its own transcription. In the present study we have introduced nonsense and deletion mutations into both genome copies of the ICP4 gene such that the resulting mutants express only defined subsets of the primary ICP4 amino acid sequence. The partial peptides retain activities and physical properties of the intact ICP4 molecule, permitting one to attribute individual activities and properties to defined amino acid sequences. Images PMID:2828668

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

    SciTech Connect

    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.

  20. Early events in herpes simplex virus type 1 infection: photosensitivity of fluorescein isothiocyanate-treated virions

    SciTech Connect

    DeLuca, N.; Bzik, D.; Person, S.; Snipes, W.

    1981-02-01

    Herpes simplex virus type 1 is photosensitized by treatment with fluorescein isothiocyanate (FITC). The inactivation of FITC-treated virions upon subsequent exposure to light is inhibited by the presence of sodium azide, suggesting the involvement of singlet oxygen in the process. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that treatment with FITC plus light induces crosslinks in viral envelope glycoproteins. Treatment of virions with high concentrations of FITC (50 ..mu..g/ml) plus light causes a reduction in the adsorption of the virus to monolayers of human embryonic lung cells. For lower concentrations of FITC (10 ..mu..g/ml) plus light, treated virions adsorb to the host cells, but remain sensitive to light until entry occurs. The loss of light sensitivity coincides with the development of resistance to antibodies. These results are most consistent with a mechanism of entry for herpes simplex virus involving fusion of the viral membrane with the plasma membrane of the host cell.

  1. Human herpes viruses are associated with classic fever of unknown origin (FUO) in Beijing patients.

    PubMed

    Zhou, Weimin; Tan, Xinyi; Li, Yamin; Tan, Wenjie

    2014-01-01

    Few reports have examined the viral aetiology of fever of unknown origin (FUO). This study determined the prevalence of human herpes virus (HHV) DNA in blood of Chinese patients with classic FUO using the polymerase chain reaction (PCR) and explored the possible role of HHV. Blood samples were collected from 186 patients (151 children, 35 adults) with classic FUO and 143 normal individuals in Beijing during the years 2009-2012. The HHV DNA, including Herpes simplex virus (HSV)-1/2, Varicella zoster virus (VZV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Human herpes virus (HHV)-6 and -7, was detected by multiplex PCR. The epidemiological and clinical features were also analysed. HHV DNA was detected in 63 (33.9%) of the FUO patients, and the prevalence of EBV and HHV-6 was significantly higher than in the normal cohort. HHV co-infection was also frequent (10.2%) in the patients with FUO. The majority of patients with HHV infection present with a fever only. Our data also revealed that EBV infection was associated with hepatitis and abnormal blood indices, HHV-6 was associated with a cough, and HHV-7 was associated with hepatitis. HHVs are associated with Chinese patients (especially for children) with classic FUO. Our study adds perspective to the aetiological and clinical characteristics of classic FUO in beijing patients.

  2. Atypical presentations of genital herpes simplex virus in HIV-1 and HIV-2 effectively treated by imiquimod.

    PubMed

    McKendry, Anna; Narayana, Srinivasulu; Browne, Rita

    2015-05-01

    Atypical presentations of genital herpes simplex virus have been described in HIV. We report two cases with hypertrophic presentations which were effectively treated with imiquimod, one of which is the first reported case occurring in a patient with HIV-2.

  3. Results From a Hypothesis Generating Case-Control Study: Herpes Family Viruses and Schizophrenia Among Military Personnel

    PubMed Central

    Niebuhr, David W.; Millikan, Amy M.; Yolken, Robert; Li, Yuanzhang; Weber, Natalya S.

    2008-01-01

    Background: Herpes family viruses can cause central nervous system inflammatory changes that can present with symptoms indistinguishable from schizophrenia and therefore are of interest in schizophrenia research. Most existing studies of herpes viruses have used small populations and postdiagnosis specimens. As part of a larger research program, we conducted a hypothesis-generating case-control study of selected herpes virus antibodies among individuals discharged from the US military with schizophrenia and pre- and postdiagnosis sera. Methods: Cases (n = 180) were servicemembers hospitalized and discharged from military service with schizophrenia. Controls, 3:1 matched on several factors, were members not discharged. The military routinely collects and stores members' serum specimens. We used microplate enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to 6 herpes viruses in pre- and postdiagnosis specimens. Conditional logistic regression was used, and the measure of association was the hazard ratio (HR). Results: Overall, we found a significant association between human herpes virus type 6 and schizophrenia, with an HR of 1.17 (95% confidence interval [CI] = 1.04, 1.32). Women and blacks had significant negative associations with herpes simplex virus type 2 and cytomegalovirus; among blacks, there was a significant positive association with herpes simplex virus type 1. Among men, there was a HHV-6 temporal effect with an HR of 1.41 (95% CI = 1.02, 1.96) for sera drawn 6–12 months before diagnosis. Discussion: Findings from previous studies of herpes family viruses and schizophrenia have been inconsistent. Our study is based on a larger population than most previous studies and used serum specimens collected before onset of illness. This study adds to the body of knowledge and provides testable hypotheses for follow-on studies. PMID:18156638

  4. Genital Herpes

    MedlinePlus

    ... a sexually transmitted disease (STD) caused by a herpes simplex virus (HSV). It can cause sores on your genital or rectal area, buttocks, and thighs. You can get it from having vaginal, anal, or ... of herpes are called outbreaks. You usually get sores near ...

  5. Double encephalitis with herpes simplex virus type II and cytomegalovirus in an elder Chinese: a case report

    PubMed Central

    Xue, Chaobiao; Chen, Shaoxian; Lin, Qi; Zhou, Houshi; Huang, Chuming; Lin, Jiyuan; Xie, Weihang; Chen, Kai; Zhou, Dongming; Ma, Wan; Ma, Feiyu; Xu, Haiyun

    2015-01-01

    Herpes simplex encephalitis is a rare disease. In adults, most of the reported cytomegalovirus (CMV) infections are seen in immunocompromised patients. We present a case of 67-year-old Chinese male with the coinfection of CMV and herpes simplex virus type II (HSV-II). He had no history of being treated with immunosuppressants, showed symptoms of psychosis and was scored 109 on the Positive and Negative Syndrome Scale. This patient presented with a rare case of coinfection of CMV and herpes simplex virus type II with psychotic symptoms. PMID:26586947

  6. Two paths for dissemination of Herpes simplex virus from infected trigeminal ganglion to the murine cornea.

    PubMed

    Ohara, P T; Tauscher, A N; LaVail, J H

    2001-04-27

    Herpes simplex virus type 1 (HSV) was introduced into the mouse trigeminal ganglion by stereotaxic injection. We examined the form in which the virus was transported anterograde within axons and the spread of virus to glial and endoneurial cells of the nerve using EM immunocytochemistry. Our results indicate that viral dissemination in the trigeminal nerve may occur both within the axon and in the extracellular space of the endoneurium. HSV is intraaxonally transported at least in part as a nucleocapsid, i.e., with neither viral envelope nor additional cellular membranes. Schwann cells are infected as a result of spread in the endoneurium, as well as by nearby axons.

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

    PubMed

    Sokolowski, Nicolas As; Rizos, Helen; Diefenbach, Russell J

    2015-01-01

    Oncolytic virotherapy exploits the properties of human viruses to naturally 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.

  8. Agents and strategies in development for improved management of herpes simplex virus infection and disease.

    PubMed

    Kleymann, Gerald

    2005-02-01

    The quiet pandemic of herpes simplex virus (HSV) infections has plagued humanity since ancient times, causing mucocutaneous infection such as herpes labialis and herpes genitalis. Disease symptoms often interfere with every-day activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immuno-compromised patient population. After infection the virus persists for life in neurons of the host in a latent form, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently no cure is available. So far, vaccines, ILs, IFNs, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or non-specific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir, penciclovir and famciclovir as the first choice of treatment. The recently discovered inhibitors of the HSV helicase-primase are the most potent development candidates today. These antiviral agents act by a novel mechanism of action and display low resistance rates in vitro and superior efficacy in animal models. This review summarises the current therapeutic options, discusses the potential of preclinical or investigational drugs and provides an up-to-date interpretation of the challenge to establish novel treatments for herpes simplex disease.

  9. Immunization with a highly attenuated replication-competent herpes simplex virus type 1 mutant, HF10, protects mice from genital disease caused by herpes simplex virus type 2.

    PubMed

    Luo, Chenhong; Goshima, Fumi; Kamakura, Maki; Mutoh, Yoshifumi; Iwata, Seiko; Kimura, Hiroshi; Nishiyama, Yukihiro

    2012-01-01

    Genital herpes is an intractable disease caused mainly by herpes simplex virus (HSV) type 2 (HSV-2), and is a major concern in public health. A previous infection with HSV type 1 (HSV-1) enhances protection against primary HSV-2 infection to some extent. In this study, we evaluated the ability of HF10, a naturally occurring replication-competent HSV-1 mutant, to protect against genital infection in mice caused by HSV-2. Subcutaneous inoculation of HF10-immunized mice against lethal infection by HSV-2, and attenuated the development of genital ulcer diseases. Immunization with HF10 inhibited HSV-2 replication in the mouse vagina, reduced local inflammation, controlled emergence of neurological dysfunctions of HSV-2 infection, and increased survival. In HF10-immunized mice, we observed rapid and increased production of interferon-γ in the vagina in response to HSV-2 infection, and numerous CD4(+) and a few CD8(+) T cells localized to the infective focus. CD4(+) T cells invaded the mucosal subepithelial lamina propria. Thus, the protective effect of HF10 was related to induction of cellular immunity, mediated primarily by Th1 CD4(+) cells. These data indicate that the live attenuated HSV-1 mutant strain HF10 is a promising candidate antigen for a vaccine against genital herpes caused by HSV-2.

  10. [Intraocular fluid antibody quotients following inoculation with two different antigens in experimental herpes simplex virus retinochoroiditis].

    PubMed

    Rai, T; Takamura, K; Ichikawa, T; Usui, M

    1989-05-01

    Viral retinochoroiditis was induced experimentally by inoculation of herpes simplex virus into the vitreous body in rabbits. The animals were sensitized systemically using 2 pathogens as antigens (herpes simplex virus and toxoplasma gondii) 3 weeks prior to intraocular inoculation. Serum and intraocular fluid were collected 2 weeks after inoculation. The intraocular fluid antibody titers and quotients for these 2 pathogens were then measured to determine the effects of serum antibodies, which are thought to enter the eyes as a result of destruction of the blood-ocular barrier. Experimental criteria for antibody quotients were also determined. Antibody quotients for the etiological virus (herpes simplex virus) ranged from 2 to 20, with an average of 9.7. Those for toxoplasma gondii, the antibody of which is thought to enter the eye from the blood, were all less than 5 with average of 1.9. From these results, it would seem that when the antibody quotient of a pathogen in more than 6 in the intraocular fluid, it is likely to be an etiological organism, while the possibility of infection is very low when the quotient is under 2. More precise studies are required to identify an etiological pathogen when the quotient is 2-6.

  11. Defining nervous system susceptibility during acute and latent herpes simplex virus-1 infection.

    PubMed

    Menendez, Chandra M; Carr, Daniel J J

    2017-07-15

    Herpes simplex viruses are neurotropic human pathogens that infect and establish latency in peripheral sensory neurons of the host. Herpes Simplex Virus-1 (HSV-1) readily infects the facial mucosa that can result in the establishment of a latent infection in the sensory neurons of the trigeminal ganglia (TG). From latency, HSV-1 can reactivate and cause peripheral pathology following anterograde trafficking from sensory neurons. Under rare circumstances, HSV-1 can migrate into the central nervous system (CNS) and cause Herpes Simplex Encephalitis (HSE), a devastating disease of the CNS. It is unclear whether HSE is the result of viral reactivation within the TG, from direct primary infection of the olfactory mucosa, or from other infected CNS neurons. Areas of the brain that are susceptible to HSV-1 during acute infection are ill-defined. Furthermore, whether the CNS is a true reservoir of viral latency following clearance of virus during acute infection is unknown. In this context, this review will identify sites within the brain that are susceptible to acute infection and harbor latent virus. In addition, we will also address findings of HSV-1 lytic gene expression during latency and comment on the pathophysiological consequences HSV-1 infection may have on long-term neurologic performance in animal models and humans. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  13. Cell autonomous regulation of herpes and influenza virus infection by the circadian clock

    PubMed Central

    Edgar, Rachel S.; Stangherlin, Alessandra; Nagy, Andras D.; Nicoll, Michael P.; Efstathiou, Stacey; O’Neill, John S.; Reddy, Akhilesh B.

    2016-01-01

    Viruses are intracellular pathogens that hijack host cell machinery and resources to replicate. Rather than being constant, host physiology is rhythmic, undergoing circadian (∼24 h) oscillations in many virus-relevant pathways, but whether daily rhythms impact on viral replication is unknown. We find that the time of day of host infection regulates virus progression in live mice and individual cells. Furthermore, we demonstrate that herpes and influenza A virus infections are enhanced when host circadian rhythms are abolished by disrupting the key clock gene transcription factor Bmal1. Intracellular trafficking, biosynthetic processes, protein synthesis, and chromatin assembly all contribute to circadian regulation of virus infection. Moreover, herpesviruses differentially target components of the molecular circadian clockwork. Our work demonstrates that viruses exploit the clockwork for their own gain and that the clock represents a novel target for modulating viral replication that extends beyond any single family of these ubiquitous pathogens. PMID:27528682

  14. Comparison of biological, biochemical, immunological, and immunochemical techniques for typing herpes simplex virus isolates.

    PubMed Central

    Zheng, Z M; Mayo, D R; Hsiung, G D

    1983-01-01

    In this study, 102 herpes simplex virus isolates were typed by cell culture selection (chicken embryo cells and guinea pig embryo cells [CE/GPE]), (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) sensitivity, plaque reduction neutralization, and indirect immunofluorescence staining techniques. The percentages of agreement between the typing methods were as follows: BVDU sensitivity versus CE/GPE, 99% (99/102); CE/GPE and BVDU sensitivity versus neutralization, 32% (33/102); CE/GPE and BVDU sensitivity versus indirect immunofluorescence staining 17% (17/102). Results were easy to interpret when the CE/GPE and BVDU sensitivity systems were used. In contrast, when type-specific antisera prepared commercially were used, results were often obscure, even contradictory, because of antibody cross-reactions. Therefore, this study suggests that immunological and immunochemical methods that use presently available commercially prepared antisera cannot reliably differentiate herpes simplex virus type 1 from type 2. PMID:6302130

  15. Herpes virus-like sequences are specifically found in Kaposi sarcoma lesions.

    PubMed Central

    O'Neill, E; Henson, T H; Ghorbani, A J; Land, M A; Webber, B L; Garcia, J V

    1996-01-01

    AIM: To detect the prevalence of herpes virus-like DNA sequences in AIDS associated Kaposi sarcoma (KSHV) lesions and normal tissue. METHODS: KSHV detection was performed by polymerase chain reaction (PCR) using four different sets of primers. PCR products were cloned, sequenced, and analysed. RESULTS: All of four biopsies of Kaposi sarcoma lesions and all of three paraffin embedded Kaposi sarcoma tissues were positive for KSHV, while normal tissue from the same patients was negative. Sequence analysis of amplification products revealed polymorphisms that result in amino acid changes of the predicted sequence. CONCLUSIONS: KSHV is prevalent in tissues from Kaposi sarcoma, suggesting a role in the development of the tumour. On this basis, anti-herpes virus agents should be considered to control Kaposi sarcoma. Images PMID:8655706

  16. Acute herpes simplex virus 1 pneumonitis in a patient with systemic lupus erythematosus.

    PubMed

    Sabugo, Francisca; Espinoza-Araya, Ricardo; Meneses, Manuel F; Cuchacovich, Miguel

    2014-01-01

    A woman with severe and longstanding systemic lupus erythematosus presented with a 1-week history of fever up to 38°C and pain in her right flank. Computed tomography scan of the chest revealed interstitial infiltrates and multiple nodules. Bronchoalveolar lavage did not show any inflammatory cells. Gram stain and cultures for aerobic and anaerobic bacteria, fungi, and Nocardia; acid-fast staining; polymerase chain reaction for tuberculosis, cytomegalovirus, herpesvirus 6, and parvovirus B19; and IF staining for pneumocystic and Legionella antigen were all negative. Transbronchial biopsy was nondiagnostic. Open lung biopsy with polymerase chain reaction and immunohistochemistry analyses revealed herpes simplex virus 1 infection. Acyclovir therapy was initiated and was followed by significant improvement. Herpes simplex virus 1 infection (although unusual) should be considered in patients with systemic lupus erythematosus with an atypical clinical presentation.

  17. Control of herpes simplex virus infections of the genital tract by vaccination.

    PubMed

    Buchan, A; Skinner, G R; Fuller, A; Hartley, C; Hallworth, J; Stocker, D; Melling, J; Wiblin, C

    1985-03-01

    The apparent increasing incidence of herpes simplex virus infections of the genital tract has focused attention on the efficacy of vaccination in preventing infection or modifying established disease. Results of an 'open trial' using a DNA-free inactivated virus subunit vaccine have shown that vaccination of subjects at risk of contracting infection from their sexual partner reduced the transmission rate from 34% in unvaccinated controls to 0.5%. In a separate study, vaccination of patients who had experienced their first overt attack of herpes genitalis (the initial clinical episode) had significantly fewer recurrences over the follow-up period of 12 months than the unvaccinated control group. The results, we feel, justify a placebo controlled trial.

  18. EFFECT OF REPEATED FREEZING (-185 degrees C.) AND THAWING ON COLON BACILLI, VIRUS III, VACCINE VIRUS, HERPES VIRUS, BACTERIOPHAGE, COMPLEMENT, AND TRYPSIN.

    PubMed

    Rivers, T M

    1927-01-01

    Colon bacilli, Virus III, vaccine virus, herpes virus, bacteriophage, complement, and trypsin are either killed or inactivated by repeated freezing (-185 degrees C.) and thawing. As might be expected, some of the agents are more resistant than others. Hence it may be concluded that destruction or inactivation of an active agent by repeated freezing (-185 degrees C.) and thawing is not proof that it was possessed of life.

  19. EFFECT OF REPEATED FREEZING (–185°C.) AND THAWING ON COLON BACILLI, VIRUS III, VACCINE VIRUS, HERPES VIRUS, BACTERIOPHAGE, COMPLEMENT, AND TRYPSIN

    PubMed Central

    Rivers, T. M.

    1927-01-01

    Colon bacilli, Virus III, vaccine virus, herpes virus, bacteriophage, complement, and trypsin are either killed or inactivated by repeated freezing (–185°C.) and thawing. As might be expected, some of the agents are more resistant than others. Hence it may be concluded that destruction or inactivation of an active agent by repeated freezing (–185°C.) and thawing is not proof that it was possessed of life. PMID:19869231

  20. Identification of new protein kinase-related genes in three herpesviruses, herpes simplex virus, varicella-zoster virus, and Epstein-Barr virus.

    PubMed Central

    Smith, R F; Smith, T F

    1989-01-01

    By using amino acid sequence patterns (motifs) diagnostic of conserved regions within the catalytic domains of protein kinases, homologous open reading frames of three herpesviruses were identified as protein kinase-related genes. The three sequences, herpes simplex virus gene UL13, varicella-zoster virus gene 47, and Epstein-Barr virus gene BGLF4, resemble serine/threonine kinases rather than tyrosine kinases. PMID:2535748

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  4. Opsoclonus-myoclonus syndrome associated with human herpes virus-6 rhomboencephalitis.

    PubMed

    Belcastro, Vincenzo; Piola, Mirko; Binda, Sandro; Santoro, Domenico; Rezzonico, Monica; Arnaboldi, Marco

    2014-06-15

    Opsoclonus-myoclonus syndrome (OMS) is characterized by opsoclonus and arrhythmic-action myoclonus that predominantly involves the trunk, limbs, and head. Human herpes virus-6 (HHV-6) can rarely cause encephalitis in immunocompetent children and adults. Here we report on a case of OMS associated with HHV-6 rhomboencephalitis. HHV-6 infection should be considered in OMS adults and detection of cell-free viral DNA, indicative of active infection, is mandatory in such cases.

  5. An immuno-enzymatic assay for herpes simplex virus tumour associated antigen in gynecological oncology.

    PubMed

    Magli, G; Scimone, C; Flaminio, G; D'Alessandro, G; Mascolo, A; Magli, R; Saladino, I

    1982-01-01

    The authors studied the HSV-TAA (Herpes Simplex Virus Tumor Associated Antigen) in patients affected by female genitale tract tumors, using the immunoenzymatic assay (ELISA). They found a positive frequence of 65% in sera of patients affected by uterine cervical carcinoma and of the 80% in sera of patients affected by vulvar carcinoma. The authors suggest that this enzymatic method has a real value and propose its use in the early diagnosis of the female genital tract neoplasms.

  6. Exposure to Herpes Simplex Virus Type 1 and Cognitive Impairments in Individuals With Schizophrenia

    PubMed Central

    Prasad, Konasale M.; Watson, Annie M. M.; Dickerson, Faith B.; Yolken, Robert H.; Nimgaonkar, Vishwajit L.

    2012-01-01

    Latent infection with neurotropic herpes viruses, such as herpes simplex virus, type 1 (HSV1), has been generally considered benign in most immunocompetent individuals except for rare cases of encephalitis. However, several recent studies have shown impaired cognitive functions among individuals with schizophrenia exposed to HSV1 compared with schizophrenia patients not exposed to HSV1. Such impairments are robust and are prominently observed in working memory, verbal memory, and executive functions. Brain regions that play a key role in the regulation of these domains have shown smaller volumes, along with correlation between these morphometric changes and cognitive impairments in schizophrenia. One study noted temporal decline in executive function and gray matter loss among HSV1-exposed first-episode antipsychotic-naïve schizophrenia patients. Furthermore, a proof-of-concept double-blind placebo-controlled trial indicated improvement in cognitive performance following supplemental anti-herpes–specific medication among HSV1 seropositive schizophrenia patients. Cross-sectional studies have also identified an association between HSV1 exposure and lesser degrees of cognitive impairment among healthy control individuals and patients with bipolar disorder. These studies fulfill several Bradford-Hill criteria, suggesting etiological links between HSV1 exposure and cognitive impairment. Exposure to other human herpes viruses such as cytomegalovirus and herpes simplex virus type 2 (HSV2) may also be associated with cognitive impairment, but the data are less consistent. These studies are reviewed critically and further lines of enquiry recommended. The results are important from a public health perspective, as HSV1 exposure is highly prevalent in many populations. PMID:22490995

  7. Association between herpes simplex virus-1 infection and idiopathic unilateral facial paralysis in children and adolescents.

    PubMed

    Khine, Hnin; Mayers, Marguerite; Avner, Jeffrey R; Fox, Amy; Herold, Betsy; Goldman, David L

    2008-05-01

    We studied the association between herpes simplex virus-1 (HSV-1) infection and Bell palsy in children. Thirty-three of 42 affected patients had a positive HSV-1 enzyme-linked immunosorbent assay compared with 16 of 41 controls (P = 0.0003). Ten of 47 affected patients had a positive HSV-1 polymerase chain reaction compared with 4 of 45 of controls (P = 0.08). Our findings support an association between HSV-1 infection and Bell palsy in children.

  8. Tracing of the molecular remnants of herpes virus infections in necrotic skin tissue.

    PubMed

    Yamamoto, Takenobu; Yamada, Akiko; Tsuji, Kazuhide; Iwatsuki, Keiji

    2008-01-01

    We have established an assay system to detect herpesvirus-derived transcripts in lesional crusts. Fifteen patients with herpes simplex (HS), 21 with herpes zoster (HZ), 2 with varicella, and 20 with irrelevant diseases were enrolled in the present study. Total RNA was extracted from crusts or scales, and converted to cDNA. Virus-encoded transcripts were amplified using reverse transcriptase (RT)-PCR. Housekeeping gene transcripts such as beta2-microglobulin (beta2-MG) and beta-actin (beta-actin) mRNA were also examined, and an efficient preservative condition of the crusts was determined. With extracted RNAs, beta2-MG and beta-actin mRNA were successfully amplified in all crust samples. Herpes simplex virus (HSV)-specific, lytic cycle-related transcript, UL30 mRNA was detected in all 15 HS samples, including 13 samples of HSV-1- and 2 of HSV-2-encoded UL30 mRNA, respectively. Of 23 samples, including 21 HZ and 2 varicella cases, varicella zoster virus (VZV)-specific, lytic cycle-related transcript, ORF40 mRNA was detected in 22 samples. In a control group, no UL30 and ORF40 mRNA were detected. Crust samples that had been stored without any pretreatment or preservative for 6 months at room temperature (RT) were available for the present assay. When compared with the freshly obtained materials, the amount of beta2-MG mRNA was reduced to 51% in the stored samples covered with adhesive tape, to 48% in a sample left at R.T. without any treatment, and to 1.2% in the samples stocked in saline for 5 days. Herpes virus- and host-derived transcripts contained in crusts can be detected by RT-PCR amplification. Crusts or dry epidermal necrosis with inflammatory cells may provide beneficial diagnostic information.

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

    PubMed

    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.

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  11. Ascending in utero herpes simplex virus infection in an initially healthy-appearing premature infant.

    PubMed

    Edwards, Morven S; Popek, Edwina J; Wise, Brittany; Hatzenbuehler, Lindsay; Arunachalam, Athis R; Hair, Amy B

    2015-01-01

    The usual route of acquisition for intrauterine herpes simplex virus (HSV) infection is transplacental. We evaluated a premature infant with in utero acquisition of HSV resulting from ascending infection. Histopathologic evidence of chronic chorioamnionitis and positive staining with immunohistochemistry for HSV in the placenta and umbilical cord established the diagnosis. The clinical presentation was also of interest in that the infant was initially healthy appearing.

  12. Detection of Human Herpes Virus 8 in Kaposi's sarcoma tissues at the University Teaching Hospital, Lusaka, Zambia.

    PubMed

    Tembo, Rabecca; Kaile, Trevor; Kafita, Doris; Chisanga, Chrispin; Kalonda, Annie; Zulu, Ephraim; Samutela, Mulemba; Polepole, Pascal; Kwenda, Geoffrey

    2017-01-01

    Human herpes virus-8, a γ2-herpes virus, is the aetiological agent of Kaposi sarcoma. Recently, Kaposi's sarcoma cases have increased in Zambia. However, the diagnosis of this disease is based on morphological appearance of affected tissues using histological techniques, and the association with its causative agent, Human Herpes virus 8 is not sought. This means poor prognosis for affected patients since the causative agent is not targeted during diagnosis and KS lesions may be mistaken for other reactive and neoplastic vascular proliferations when only histological techniques are used. Therefore, this study was aimed at providing evidence of Human Herpes virus 8 infection in Kaposi's sarcoma tissues at the University Teaching Hospital in Lusaka, Zambia. One hundred and twenty suspected Kaposi's sarcoma archival formalin-fixed paraffin-wax embedded tissues stored from January 2013 to December 2014 in the Histopathology Laboratory at the University Teaching Hospital, Lusaka, Zambia were analysed using histology and Polymerase Chain Reaction targeting the ORF26 gene of Human Herpes virus 8. The predominant histological type of Kaposi's sarcoma detected was the Nodular type (60.7%) followed by the plaque type (22.6%) and patch type (16.7%). The nodular lesion was identified mostly in males (40.5%, 34/84) than females (20.2%, 17/84) (p=0.041). Human Herpes virus 8 DNA was detected in 53.6% (45/84) and mostly in the nodular KS lesions (60%, 27/84) (p=0.035). The findings in this study show that the Human Herpes virus-8 is detectable in Kaposi's sarcoma tissues, and, as previously reported in other settings, is closely associated with Kaposi's sarcoma. The study has provided important baseline data for use in the diagnosis of this disease and the identification of the virus in the tissues will aid in targeted therapy.

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

    PubMed Central

    Bertke, Andrea S.

    2017-01-01

    Purpose 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. Methods 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. Results 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. Conclusion 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. Implications and contribution These studies provide information on knowledge of herpes simplex viruses

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

    PubMed

    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

  15. The treatment of herpes simplex virus epithelial keratitis.

    PubMed Central

    Wilhelmus, K R

    2000-01-01

    PURPOSE: Epithelial keratitis is the most common presentation of ocular infection by herpes simplex virus (HSV). Quantitative assessment of available therapy is needed to guide evidence-based ophthalmology. This study aimed to compare the efficacy of various treatments for dendritic or geographic HSV epithelial keratitis and to evaluate the role of various clinical characteristics on epithelial healing. METHODS: Following a systematic review of the literature, information from clinical trials of HSV dendritic or geographic epithelial keratitis was extracted, and the methodological quality of each study was scored. Methods of epithelial cauterization and curettage were grouped as relatively equivalent physicochemical therapy, and solution and ointment formulations of a given topical antiviral agent were combined. The proportion healed with 1 week of therapy, a scheduled follow-up day that approximated the average time of resolution with antiviral therapy, was selected as the primary outcome based on a masked evaluation of maximum treatment differences in published healing curves. The proportion healed at 14 days was recorded as supplemental information. Fixed-effects and random-effects meta-analysis models were used to obtain summary estimates by pooling results from comparative treatment trials. Hypotheses about which prognostic factors might affect epithelial healing during antiviral therapy were developed by multivariate analysis of the Herpetic Eye Disease Study dataset. RESULTS: After excluding 48 duplicate reports, 14 nonrandomized studies, 15 studies with outdated or similar treatments, and 29 trials lacking sufficient data on healing or accessibility, 76 primary reports were identified. These reports involved 4,251 patients allocated to 93 treatment comparisons of dendritic epithelial keratitis in 28 categories and 9 comparisons of geographic epithelial keratitis in 6 categories. For dendritic keratitis, idoxuridine was better than placebo at 7 days

  16. Marrow-dependent cells depleted by 89Sr mediate genetic resistance to herpes simplex virus type 1 infection in mice.

    PubMed

    Lopez, C; Ryshke, R; Bennett, M

    1980-06-01

    Adult mice resistant to infection with 10(6) plaque-forming units of a virulent strain of herpes simplex virus type 1 were treated with 89Sr to abrogate marrow-dependent cell functions. Treated mice were found to be much more susceptible to the herpes simplex virus type 1 infection than untreated mice. The virus persisted in the visceral tissues of 89Sr-treated mice for 3 or more days postinfection but not in those of untreated mice. The virus also spread to the spinal cords of treated but not untreated mice. A marrow-dependent cell appeared to mediate resistance to herpes simplex virus type 1 by controlling the infection early after inoculation and not allowing the infection spread to the central nervous system.

  17. Lethargy, ulcers, bronchopneumonia and death in two aged female bonnet macaques presumed to be caused by Cercopithicine herpes virus I.

    PubMed

    Scharf, Bruce A; Wan, Cho-Hua; Bluth, Martin; Eberle, Richard; Videan, Elaine N; Smith, Eric; Coplan, Jeremy

    2008-02-01

    Over the course of 4 weeks, two female aged bonnet macaque (Macaca radiata) group-housed females died after the dominant male was removed from the group and the newly dominant male persistently chased, caught and bred all females in the pen. The two aged affected females were observed exhibiting lethargy, dyspnea, with widespread necroulcerative lesions in and around the mouth, muzzle and bridge of their noses. Extensive ulcerative glossitis, necrotic bronchopneumonia with intra-nuclear inclusions and the absence of other evidence is highly suggestive that death was caused by an alphaherpes virus commonly known as herpes B virus. Herpes B virus is a potentially zoonotic disease periodically shed by macaques, which is structurally related to herpes simplex viruses I and II of humans. The emergence of fatal B virus to primates in this pen may have been associated with the combination of age and stress in the affected individuals.

  18. Lymphoproliferative response to herpes simplex virus type 1, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, human herpes virus 6, 7, and 8 antigen stimulation in pediatric allogeneic stem cell transplant recipients.

    PubMed

    Cheng, Frankie Wai Tsoi; Chan, Paul Kay Sheung; Lee, Vincent; Leung, Wing Kwan; Shing, Ming Kong; Li, Chi Kong; Leung, Ting Fan

    2010-09-01

    We evaluate the recovery of CMI to various herpes viruses by measuring in vitro LPR to specific recall antigens. CMI was evaluated by the in vitro LPR of PBMC to specific purified HSV-1, VZV, CMV, EBV, HHV-6, -7, -8, antigens. Results were expressed as SI. SI > or = 3 was regarded as positive LPR. Serial measurements were taken prospectively from pretransplant till 12-month post-transplant. Thirty-six patients (M = 19; F = 17) with median age 10.5 yr old were recruited. Most transplants were from MSD with PBSC as the stem cell source. Altogether 50% of subjects started to show positive LPR to HSV-1, CMV, and VZV antigens at two-month post-transplant, major upsurges were noted until 6-month post-transplant. Subjects showed positive LPR to EBV, HHV-6, HHV-7, and HHV-8 antigens were all along <50% throughout the study period. The antibody status of donor and recipient for HSV-1, CMV, and VZV were associated with the timing of recovery of CMI. Choice of donor and stem cell source were important determinants of eventual LPR to various herpes viruses at 3-month post-transplant. At 12-month post-transplant, there was no statistical difference in any parameters in affecting LPR to different herpes viruses.

  19. Improved DNA hybridization method for detection of acyclovir-resistant herpes simplex virus.

    PubMed Central

    Swierkosz, E M; Scholl, D R; Brown, J L; Jollick, J D; Gleaves, C A

    1987-01-01

    A simplified DNA hybridization method was developed to detect acyclovir-resistant isolates of herpes simplex virus. Herpes simplex virus-infected cell cultures in microtiter plates were treated with concentrations of acyclovir ranging from 8 to 0.015 micrograms/ml. At 48 h postinfection, infected cells were lysed by a one-step procedure and lysates were absorbed to membranes. Without further treatment, membranes were hybridized by using a herpes simplex virus-specific radioiodinated probe. The membranes were then washed and counted in a gamma counter. The elapsed time for assay performance was 4 h. Parallel plaque reduction assays were performed for comparison. The mean 50% inhibitory dose of in vivo- and in vitro-derived acyclovir-resistant, thymidine kinase-negative isolates was greater than 2 micrograms/ml by DNA hybridization. The 50% inhibitory dose of acyclovir-susceptible, thymidine kinase-positive isolates ranged from 0.01 to 1.1 micrograms/ml. This assay is simple and objective and should facilitate antiviral susceptibility testing in diagnostic laboratories. PMID:2829708

  20. Potential role of tenofovir vaginal gel for reduction of risk of herpes simplex virus in females

    PubMed Central

    Tan, DHS

    2012-01-01

    A surprising result of the groundbreaking CAPRISA-004 trial, which demonstrated the efficacy of vaginal tenofovir 1% gel in reducing the risk of human immunodeficiency virus (HIV)-1 infection by 39% in heterosexual women, was the added benefit of this microbicide in reducing acquisition of herpes simplex virus type 2 (HSV-2) by 51%. HSV-2 is the most common cause of genital ulcer disease worldwide, and is responsible for considerable morbidity among women and neonates. The virus is further implicated in increasing the risk of both HIV acquisition and transmission, and may have additional adverse consequences in HIV-coinfected persons, making HSV-2 prevention an important clinical and public health objective. While tenofovir had not previously been widely considered to be an anti-herpes drug, in vitro activity against HSV is well documented, raising interest in potential future applications of tenofovir and its prodrugs in HSV-2 control. This article reviews the currently available data for tenofovir as an anti-herpes agent, as well as unanswered questions about delivery systems, drug formulation, rectal administration, drug resistance, and clinical applications. PMID:22927765

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

    PubMed Central

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

    2015-01-01

    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 in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections. PMID:23331181

  2. Update on emerging antivirals for the management of herpes simplex virus infections: a patenting perspective.

    PubMed

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

    2013-04-01

    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 in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections.

  3. Association between malaria exposure and Kaposi's sarcoma-associated herpes virus seropositivity in Uganda

    PubMed Central

    Nalwoga, Angela; Cose, Stephen; Wakeham, Katie; Miley, Wendell; Ndibazza, Juliet; Drakeley, Christopher; Elliott, Alison; Whitby, Denise; Newton, Robert

    2015-01-01

    Objective Unlike other herpes viruses, Kaposi's sarcoma-associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV. Methods Antibodies against P. falciparum merozoite surface protein (PfMSP)-1, P. falciparum apical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children. Results Kaposi's sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP-1 and PfAMA-1, respectively (P < 0.0001). Among children, only antibodies to PfAMA-1 were significantly associated with KSHV seropositivity, (P < 0.0001). In both mothers and children, anti-ORF73 antibodies were more strongly associated with malaria antibodies than anti-K8.1 antibodies. Conclusion The association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation. PMID:25611008

  4. Deletions in herpes simplex virus glycoprotein D define nonessential and essential domains.

    PubMed Central

    Feenstra, V; Hodaie, M; Johnson, D C

    1990-01-01

    Herpes simplex virus glycoprotein D (gD) is a major component of the virion envelope and infected cell membranes and is essential for virus entry into cells. We have recently shown that gD interacts with a limited number of cell surface receptors which are required for virus penetration into cells. To define domains of gD which are required for aspects of virus replication including receptor binding, deletion mutations of 5 to 14 amino acids were constructed by using oligonucleotide-directed mutagenesis. Plasmids containing mutant genes for gD were assayed for the ability to rescue a recombinant virus, F-gD beta, in which beta-galactosidase sequences replace gD-coding sequences. Effects on global folding and posttranslational processing of the molecules were assessed by using a panel of monoclonal antibodies which recognize both continuous and discontinuous epitopes. A region near the amino terminus (residues 7 to 21) of gD which is recognized by monoclonal antibodies able to neutralize herpes simplex virus in the absence of complement was not essential for function. In addition, virtually all of the cytoplasmic domain of gD and an extracellular domain close to the membrane were dispensable. In contrast, deletion mutations in the central region of the molecule, save for one exception, led to alterations in global folding of the molecule and maturation of the protein was inhibited. Images PMID:2157872

  5. Reactivation of latent herpes viruses in cosmonauts during a soyuz taxi mission

    NASA Astrophysics Data System (ADS)

    Mehta, Satish K.; Pierson, Duane L.

    2007-09-01

    The hypothesis tested by this project is that space flight increases the incidence and duration of herpes virus reactivation and shedding in saliva. Saliva, urine, and blood samples were collected from 3 crew members who participated in a 14-day Odessa Soyuz taxi mission. Saliva samples were collected before, during, and after the mission, and blood and urine were collected before and after the mission. The saliva and urine samples were analyzed using the polymerase chain reaction to detect the presence of 3 important herpes viruses. Epstein-Barr virus (EBV) and varicella-zoster virus (VZV) were tested in saliva, and cytomegalovirus (CMV) was measured in urine samples. Plasma antibodies levels to these viruses were determined by enzyme-linked immunosorbent assay before and after flight. EBV reactivated before, during, and after flight; CMV reactivated before and after flight; and VZV reactivated during and after flight. In other studies, greater frequencies of positive samples and greater numbers of copies of viral DNA have been found. No increases in titer of antibodies to these viruses were found, suggesting that an immune response may not be necessary for reactivation.

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

    PubMed

    Ray, Aniruddha; Daloglu, Mustafa Ugur; Ho, Joslynn; Torres, Avee; Mcleod, Euan; Ozcan, Aydogan

    2017-07-07

    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 mm(2). 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.

  7. Live-cell analysis of a green fluorescent protein-tagged herpes simplex virus infection.

    PubMed

    Elliott, G; O'Hare, P

    1999-05-01

    Many stages of the herpes simplex virus maturation pathway have not yet been defined. In particular, little is known about the assembly of the virion tegument compartment and its subsequent incorporation into maturing virus particles. Here we describe the construction of a herpes simplex virus type 1 (HSV-1) recombinant in which we have replaced the gene encoding a major tegument protein, VP22, with a gene expressing a green fluorescent protein (GFP)-VP22 fusion protein (GFP-22). We show that this virus has growth properties identical to those of the parental virus and that newly synthesized GFP-22 is detectable in live cells as early as 3 h postinfection. Moreover, we show that GFP-22 is incorporated into the HSV-1 virion as efficiently as VP22, resulting in particles which are visible by fluorescence microscopy. Consequently, we have used time lapse confocal microscopy to monitor GFP-22 in live-cell infection, and we present time lapse animations of GFP-22 localization throughout the virus life cycle. These animations demonstrate that GFP-22 is present in a diffuse cytoplasmic location when it is initially expressed but evolves into particulate material which travels through an exclusively cytoplasmic pathway to the cell periphery. In this way, we have for the first time visualized the trafficking of a herpesvirus structural component within live, infected cells.

  8. Isolation and characterization of two new herpes-like viruses from capuchin monkeys.

    PubMed

    Lewis, M A; Frye, L D; Gibbs, C J; Chou, S M; Cutchins, E C; Gajdusek, D C; Ward, G

    1976-09-01

    Two herpes-like viruses were isolated from capuchin monkey (Cebus apella) brain and (Cebus albifrons) spleen cell cultures, respectively. Both isolates induced similar cytopathic effects consisting of rounded and ballooned cells in the original monkey cell cultures and in a wide range of permissive cell types. Neutralizing antibody to each virus was present in serum from the capuchin monkey from which it was isolated, but the two viruses did not cross-react by neutralization. Fluorescein isothiocyanate conjugates of hyperimmune rabbit serum to one of the isolates showed an antigenic cross relationship between the two isolates. By electron microscopy, herpes-like virus particles were observed in the nucleus and cytoplasm of infected human diploid fibroblast cell cultures. Virus-infected cell cultures stained with acridine orange revealed small deoxyribonucleic acid-containing intranuclear inclusion bodies. Both viruses were inhibited by 5-fluorodeoxyuridine and inactivated by chloroform or exposure to 56 degrees C for 30 min. Antisera prepared against 16 prototype herpesviruses and cytomegaloviruses did not neutralize approximately 100 50% tissue culture infective doses of either capuchin isolate. Neutralizing antibody to the capuchin isolates was detected in sera from 8 of 17 capuchin monkeys but not in sera from 16 humans, 15 chimpanzees, and 10 spider, 6 rhesus, and 5 squirrel monkeys.

  9. Effects of dimethyl prostaglandin A1 on herpes simplex virus and human immunodeficiency virus replication

    NASA Technical Reports Server (NTRS)

    Hughes-Fulford, M.; McGrath, M. S.; Hanks, D.; Erickson, S.; Pulliam, L.

    1992-01-01

    We have investigated the direct effect of dimethyl prostaglandin A1 (dmPGA1) on the replication of herpes simplex virus (HSV) and human immunodeficiency virus type 1 (HIV-1). dmPGA1 significantly inhibited viral replication in both HSV and HIV infection systems at concentrations of dmPGA1 that did not adversely alter cellular DNA synthesis. The 50% inhibitory concentration (ID50) for several HSV type 1 (HSV-1) strains ranged from 3.8 to 5.6 micrograms/ml for Vero cells and from 4.6 to 7.3 micrograms/ml for human foreskin fibroblasts. The ID50s for two HSV-2 strains varied from 3.8 to 4.5 micrograms/ml for Vero cells; the ID50 was 5.7 micrograms/ml for human foreskin fibroblasts. We found that closely related prostaglandins did not have the same effect on the replication of HSV; dmPGE2 and dmPGA2 caused up to a 60% increase in HSV replication compared with that in untreated virus-infected cells. HIV-1 replication in acutely infected T cells (VB line) and chronically infected macrophages was assessed by quantitative decreases in p24 concentration. The effective ID50s were 2.5 micrograms/ml for VB cells acutely infected with HIV-1 and 5.2 micrograms/m for chronically infected macrophages. dmPGA1 has an unusual broad-spectrum antiviral activity against both HSV and HIV-1 in vitro and offers a new class of potential therapeutic agents for in vivo use.

  10. Effects of dimethyl prostaglandin A1 on herpes simplex virus and human immunodeficiency virus replication

    NASA Technical Reports Server (NTRS)

    Hughes-Fulford, M.; McGrath, M. S.; Hanks, D.; Erickson, S.; Pulliam, L.

    1992-01-01

    We have investigated the direct effect of dimethyl prostaglandin A1 (dmPGA1) on the replication of herpes simplex virus (HSV) and human immunodeficiency virus type 1 (HIV-1). dmPGA1 significantly inhibited viral replication in both HSV and HIV infection systems at concentrations of dmPGA1 that did not adversely alter cellular DNA synthesis. The 50% inhibitory concentration (ID50) for several HSV type 1 (HSV-1) strains ranged from 3.8 to 5.6 micrograms/ml for Vero cells and from 4.6 to 7.3 micrograms/ml for human foreskin fibroblasts. The ID50s for two HSV-2 strains varied from 3.8 to 4.5 micrograms/ml for Vero cells; the ID50 was 5.7 micrograms/ml for human foreskin fibroblasts. We found that closely related prostaglandins did not have the same effect on the replication of HSV; dmPGE2 and dmPGA2 caused up to a 60% increase in HSV replication compared with that in untreated virus-infected cells. HIV-1 replication in acutely infected T cells (VB line) and chronically infected macrophages was assessed by quantitative decreases in p24 concentration. The effective ID50s were 2.5 micrograms/ml for VB cells acutely infected with HIV-1 and 5.2 micrograms/m for chronically infected macrophages. dmPGA1 has an unusual broad-spectrum antiviral activity against both HSV and HIV-1 in vitro and offers a new class of potential therapeutic agents for in vivo use.

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

    PubMed

    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.

  12. Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans

    PubMed Central

    1992-01-01

    The role of cell surface heparan sulfate in herpes simplex virus (HSV) infection was investigated using CHO cell mutants defective in various aspects of glycosaminoglycan synthesis. Binding of radiolabeled virus to the cells and infection were assessed in mutant and wild-type cells. Virus bound efficiently to wild-type cells and initiated an abortive infection in which immediate-early or alpha viral genes were expressed, despite limited production of late viral proteins and progeny virus. Binding of virus to heparan sulfate-deficient mutant cells was severely impaired and mutant cells were resistant to HSV infection. Intermediate levels of binding and infection were observed for a CHO cell mutant that produced undersulfated heparan sulfate. These results show that heparan sulfate moieties of cell surface proteoglycans serve as receptors for HSV. PMID:1310996

  13. The Function of Herpes Simplex Virus Genes: A Primer for Genetic Engineering of Novel Vectors

    NASA Astrophysics Data System (ADS)

    Roizman, Bernard

    1996-10-01

    Herpes simplex virus vectors are being developed for delivery and expression of human genes to the central nervous system, selective destruction of cancer cells, and as carriers for genes encoding antigens that induce protective immunity against infectious agents. Vectors constructed to meet these objectives must differ from wild-type virus with respect to host range, reactivation from latency, and expression of viral genes. The vectors currently being developed are (i) helper free amplicons, (ii) replication defective viruses, and (iii) genetically engineered replication competent viruses with restricted host range. Whereas the former two types of vectors require stable, continuous cell lines expressing viral genes for their replication, the replication competent viruses will replicate on approved primary human cell strains.

  14. Vaccination of cattle against pseudorabies (Aujeszky's disease) with homologous virus (herpes suis) and heterologous virus (herpes bovis 1).

    PubMed

    Biront, P; Vandeputte, J; Pensaert, M B; Leunen, J

    1982-05-01

    Study was made to determine whether vaccination of cattle against pseudorabies (PR; Aujeszky's disease) affords protection upon subsequent intranasal challenge exposure with virulent virus. Vaccinations were performed with a commercially available oil-adjuvant PR virus vaccine, in some cases supplemented with A1(OH)3 (given subcutaneously), with the attenuated NIA4 strain of PR virus (given intranasally), and with a commercially available temperature-sensitive mutant of bovine herpesvirus-1 (infectious bovine rhinotracheitis [IBR] virus) given intranasally. Challenge exposure was performed intranasally with 10(3) median lethal doses (LD50) of the virulent PR virus. In earlier experiments, it was found that LD50 median tissue culture infective doses of this virulent PR virus in primary pig kidney cells represented about 1 LD50 for cattle. This LD50 was practically no different for cattle whether or not they had antibodies against PR virus before exposure to virulent PR virus. In the seropositive animals, antibodies were present presumably as a consequence of a previous IBR infection in the field. Vaccination intranasally with NIA4 or IBR virus did not result in serologic response or protection against challenge exposure. The inactivated-virus vaccine induced a good serologic reaction, but there was poor protection against challenge exposure. Consequently, vaccination of cattle at risk of exposure to virulent PR virus cannot be advised. In the present experiments, initiation of infection with virulent PR virus in cattle always resulted in disease and death.

  15. An in vitro evaluation of extracts from some medicinal plants in Kenya against herpes simplex virus.

    PubMed

    Kofi-Tsekpo, M W; Rukunga, G M; Kurokawa, M; Kageyama, S; Mungai, G M; Muli, J M; Tolo, F M; Kibaya, R M; Muthaura, C N; Kanyara, J N; Tukei, P M; Shiraki, K

    2001-01-01

    The extracts from 21 medicinal plants commonly used in traditional remedies in Kenya were screened for antiviral activity against wild type 7401H strain herpes simplex virus type 1. The plant extracts exhibited antiviral activity against the virus in the plaque and yield reduction assays. The results reveal that twelve plants may contain constituents that could be exploited for the management of HSV infections. Although the extracts used in these experiments contain a complex matrix of a large number of compounds the results indicate that useful compounds can be isolated for further exploitation.

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

    PubMed

    Wudiri, George A; Pritchard, Suzanne M; Li, Hong; Liu, Jin; Aguilar, Hector C; Gilk, Stacey D; Nicola, Anthony V

    2014-12-01

    Herpes simplex virus 1 (HSV-1) required cholesterol or desmosterol for virion-induced membrane fusion. HSV successfully entered DHCR24(-/-) cells, which lack a desmosterol-to-cholesterol conversion enzyme, indicating that entry can occur independently of cholesterol. Depletion of desmosterol from these cells resulted in diminished HSV-1 entry, suggesting a general sterol requirement for HSV-1 entry and that desmosterol can operate in virus entry. Cholesterol functioned more effectively than desmosterol, suggesting that the hydrocarbon tail of cholesterol influences viral entry. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  17. Role of Fc fragments in antibody-mediated recovery from ocular and subcutaneous herpes simplex virus infections.

    PubMed Central

    Oakes, J E; Lausch, R N

    1981-01-01

    The contributions of the Fc fragment of virus-specific antibody in the resistance of mice to peripheral herpes simplex virus infection were investigated. Rabbit anti-herpes simplex virus-specific F(ab')2 fragments prepared by pepsin digestion of immune immunoglobulin G (IgG) were found to be inactive in complement-mediated cytolysis while retaining their capacity to neutralize virus infectivity in vitro. When F(ab')2 fragments were passively transferred either before or simultaneously with virus inoculation, they were as efficient as intact IgG was in protecting animals from virus challenge. However, if passive transfer was delayed until 8 h after herpes simplex virus infection, only IgG antibody was protective. The loss of protective activity could not be attributed to a rapid disappearance of F(ab')2 fragments, because comparable levels of F(ab')2 fragments and IgG antibody were maintained in the blood of recipients during the time that antibody mediated its protective effects. The inability of F(ab')2 subunits to activate complement was also not a factor, because complement-deficient A/J mice and complement-sufficient SJL/J mice recovered from herpes simplex virus infection after the passive transfer of IgG. We concluded that the Fc component of the antibody molecule is needed to resolve intracellular infection and that the mechanism by which antibody mediates recovery remains undefined but does not appear to involve virus neutralization or complement activation. PMID:6266961

  18. Herpes simplex virus encephalitis is a trigger of brain autoimmunity.

    PubMed

    Armangue, Thaís; Leypoldt, Frank; Málaga, Ignacio; Raspall-Chaure, Miquel; Marti, Itxaso; Nichter, Charles; Pugh, John; Vicente-Rasoamalala, Monica; Lafuente-Hidalgo, Miguel; Macaya, Alfons; Ke, Michael; Titulaer, Maarten J; Höftberger, Romana; Sheriff, Heather; Glaser, Carol; Dalmau, Josep

    2014-02-01

    In 5 prospectively diagnosed patients with relapsing post-herpes simplex encephalitis (HSE), N-methyl-D-aspartate receptor (NMDAR) antibodies were identified. Antibody synthesis started 1 to 4 weeks after HSE, preceding the neurological relapse. Three of 5 patients improved postimmunotherapy, 1 spontaneously, and 1 has started to improve. Two additional patients with NMDAR antibodies, 9 with unknown neuronal surface antibodies, and 1 with NMDAR and unknown antibodies, were identified during retrospective assessment of 34 HSE patients; the frequency of autoantibodies increased over time (serum, p=0.004; cerebrospinal fluid, p=0.04). The 3 retrospectively identified NMDAR antibody-positive patients also had evidence of relapsing post-HSE. Overall, these findings indicate that HSE triggers NMDAR antibodies and potentially other brain autoimmunity.

  19. Reduced yield of infectious pseudorabies virus and herpes simplex virus from cell lines producing viral glycoprotein gp50.

    PubMed Central

    Petrovskis, E A; Meyer, A L; Post, L E

    1988-01-01

    Pseudorabies virus (PRV) glycoprotein gp50 is the homolog of herpes simplex virus (HSV) glycoprotein D. Several cell lines that constitutively synthesize gp50 were constructed. Vero cells, HeLa cells, and pig kidney (MVPK) cells that produce gp50 all gave reduced yields of PRV and HSV progeny viruses when compared with the parent cell line or the same cell line transfected to produce a different protein. The reduction in virus yield was greatest at low multiplicities of infection. The Vero and HeLa cells that produce gp50 showed an even greater reduction in HSV yield than in PRV yield. This phenomenon may be an example in a herpesvirus of the interference observed in retroviruses or cross-protection in plant virus systems. PMID:2835521

  20. Salivary Varicella Zoster Virus in Astronauts and in Patients of Herpes Zoster

    NASA Technical Reports Server (NTRS)

    Mehta, Satish; Pierson, Duane L.

    2010-01-01

    Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpes viruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpesviruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors? offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

  1. Herpes Simplex Virus: The Interplay Between HSV, Host, and HIV-1.

    PubMed

    Desai, Dipen Vijay; Kulkarni, Smita Shrikant

    2015-12-01

    Herpes simplex virus proteins interact with host (human) proteins and create an environment conducive for its replication. Genital ulceration due to herpes simplex virus type 2 (HSV-2) infections is an important clinical manifestation reported to increase the risk of human immunodeficiency virus type 1 (HIV-1) acquisition and replication in HIV-1/HSV-2 coinfection. Dampening the innate and adaptive immune responses of the skin-resident dendritic cells, HSV-2 not only helps itself, but creates a "yellow brick road" for one of the most dreaded viruses HIV, which is transmitted mainly through the sexual route. Although, data from clinical trials show that HSV-2 suppression reduces HIV-1 viral load, there are hardly any reports presenting conclusive evidence on the impact of HSV-2 coinfection on HIV-1 disease progression. Be that as it may, understanding the interplay between these three characters (HSV, host, and HIV-1) is imperative. This review endeavors to collate studies on the influence of HSV-derived proteins on the host response and HIV-1 replication. Studying such complex interactions may help in designing and developing common strategies for the two viruses to keep these "partners in crime" at bay.

  2. [Herpes simplex virus type 1 latency and reactivation: an update].

    PubMed

    Aranda, Alejandro M; Epstein, Alberto L

    2015-05-01

    Following primary infections HSV-1 replicates productively in epithelial cells and enters sensory neurons via nerve termini. After retrograde transport the virus genome is delivered into the cell nucleus, where it establishes lifelong latent infections. During latency, the virus genome remains as a chromatinized episome expressing only a set of latency-associated transcripts (LAT) and a group of microRNAs that inhibit expression of key lytic viral functions. Periodically the virus can reactivate to reinitiate lytic, secondary infections at peripheral tissues. The ability to establish both lytic and latent infections relies on the coexistence in the virus genome of two alternative gene expression programs, under the control of epigenetic mechanisms. Latency is an adaptive phenotype that allows the virus to escape immune host responses and to reactivate and disseminate to other hosts upon recognizing danger signals such as stress, neurologic trauma or growth factor deprivation. © 2015 médecine/sciences – Inserm.

  3. Inhibition of host protein synthesis and degradation of cellular mRNAs during infection by influenza and herpes simplex virus

    SciTech Connect

    Inglis, S.C.

    1982-12-01

    Cloned DNA copies of two cellular genes were used to monitor, by blot hybridization, the stability of particular cell mRNAs after infection by influenza virus and herpes virus. The results indicated that the inhibition of host cell protein synthesis that accompanied infection by each virus could be explained by a reduction in the amounts of cellular mRN As in the cytoplasm, and they suggested that this decrease was due to virus-mediated mRNA degradation.

  4. Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation

    PubMed Central

    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. PMID:25709648

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

    PubMed

    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.

  6. Herpes simplex virus in the saliva of peripheral Bell's palsy patients.

    PubMed

    Lazarini, Paulo Roberto; Vianna, Melissa Ferreira; Alcantara, Mônica Porto Alves; Scalia, Rodolfo Alexander; Caiaffa Filho, Hélio Hehl

    2006-01-01

    The first herpes virus to be described was types 1 and 2, whose denomination is herpes simplex 1 and 2 or HSV-1 and HSV-2. These viruses have specific biological characteristics, such as the ability to cause different kinds of diseases, as well as to establish hosts latent or persistent lifetime infections and also of being reactivated, causing lesions that can be located at the same site of the initial primary infection or close to it. It is suggested that this virus reactivation in the geniculate ganglion may be related to Bell's palsy. In this situation, the viruses that would be latent in this ganglion, would suffer reactivation and replication, then be diffused through the facial nerve and its branches, among them the chorda tympani nerve, which by stimulating salivary secretion would enable the identification of the viral DNA in the patients saliva. Until recently, a great number of patients was diagnosed as holders of this kind of paralysis, named idiopathic or Bell's palsy. With the introduction of the technique studying the viral DNA by Polymerase Chain Reaction (PCR), several authors have found herpes simplex virus type I DNA in the cerebrospinal fluid, in the lachrymal secretion, in the saliva and in the geniculate ganglia of patients with Bell's palsy. observe the occurrence of herpes simplex type I virus using PCR technique in the saliva of patients with Bell's palsy and relating it to the clinical evolution of these cases. We evaluated 38 patients with Bell's palsy submitted to anamnesis, clinical and ENT examination and saliva sampling for viral DNA detection by PCR technique. The control group was ten normal adults. We found positive viral DNA in 11 cases out of the 38, which corresponded to 29% of the sample. This result was statistically significant if compared to the control group, in which we did not find any positive case. The end result was that the presence of HSV-1 in the saliva of patients with Bell's palsy indicating that the viral

  7. Role of bovine mammillitis virus towards preparation of an alternative vaccine against herpes simplex virus infections of human subjects.

    PubMed

    Skinner, G R; Buchan, A; Durham, J; Cowan, M; Davies, J; Brookes, K; Castrucci, G

    1987-03-01

    Bovine mammillitis virus (BMV) cross-reacted in neutralization and radioimmune assay with herpes simplex virus (HSV) and pre-immunization with BMV protected against challenge by type 2 HSV. There was no evidence to suggest a pathogenic role for BMV as adjudged by a literature search or field enquiry and BMV specific antibody was not detected in 21 human sera or in four sera from personnel engaged in research with BMV; in addition there was no replication or antigen synthesis by BMV in explants of human tissue or cell lines of human origin. It is proposed that BMV might provide an alternative vaccine against HSV infections of human subjects.

  8. Association of interferon lambda-1 with herpes simplex viruses-1 and -2, Epstein-Barr virus, and human cytomegalovirus in chronic periodontitis.

    PubMed

    Muzammil; Jayanthi, D; Faizuddin, Mohamed; Noor Ahamadi, H M

    2017-05-01

    Periodontal tissues facilitate the homing of herpes viruses that elicit the immune-inflammatory response releasing the interferons (IFN). IFN lambda-1 (λ1) can suppress the replication of viruses, and induces the antiviral mechanism. The aim of the present study was to evaluate the association between IFN-λ1 and periodontal herpes viruses in the immunoregulation of chronic periodontal disease. The cross-sectional study design included 30 chronic periodontitis patients with a mean age of 42.30 ± 8.63 years. Gingival crevicular fluid collected was assessed for IFN-λ1 using enzyme-linked immunosorbent assay and four herpes viruses were detected using multiplex polymerase chain reaction technique. IFN-λ1 levels were compared between virus-positive and -negative patients for individual and total viruses. Fifty per cent (n = 15) of patients were positive for the four herpes viruses together; 50% (n = 15), 30% (n = 9), 26.7% (n = 8), and 40% (n = 12) were positive for herpes simplex virus (HSV)-1, Epstein-Barr virus, HSV-2, and human cytomegalovirus, respectively. The mean concentrations of IFN-λ1 in virus-positive patients (14.38 ± 13.95) were lower than those of virus-negative patients (228.26 ± 215.35). INF-λ1 levels in individual virus groups were also lower in virus-positive patients compared to virus-negative patients, with P < 0.001. These results suggest that IFN-λ1 could have antiviral and therapeutic value against the viruses in the pathogenesis of chronic periodontitis. © 2015 Wiley Publishing Asia Pty Ltd.

  9. Inhibitory activity of Melissa officinalis L. extract on Herpes simplex virus type 2 replication.

    PubMed

    Mazzanti, G; Battinelli, L; Pompeo, C; Serrilli, A M; Rossi, R; Sauzullo, I; Mengoni, F; Vullo, V

    2008-01-01

    Melissa officinalis L. (Lamiaceae) (lemon balm) is used in folk medicine for nervous complaints, lower abdominal disorders and, more recently, for treating Herpes simplex lesions. In this work the antiviral activity of a hydroalcoholic extract of lemon balm leaves against the Herpes simplex virus type 2 (HSV-2) was assessed by the cytopathic effect inhibition assay on Vero cells (ATCC CCL-81), in comparison with acyclovir. The cytotoxicity of the extract on Vero cells was previously tested by evaluating the cellular death and was confirmed by the Trypan blue test. Lemon balm showed to reduce the cytopathic effect of HSV-2 on Vero cells, in the range of non-toxic concentrations of 0.025-1 mg mL(-1) (with reference to the starting crude herbal material). The maximum inhibiting effect (60%) was obtained with 0.5 mg mL(-1). The viral binding assay showed that the extract does not prevent the entry of HSV-2 in the cells, thus suggesting a mechanism of action subsequent to the penetration of the virus in the cell. The extract was also chemically characterised by NMR and HPLC analysis; it showed to contain cinnamic acid-like compounds, mainly rosmarinic acid (4.1% w/w). Our experiments support the use of lemon balm for treating Herpes simplex lesions and encourage clinical trials on this medicinal plant.

  10. Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts.

    PubMed

    Itzhaki, Ruth F

    2017-08-01

    Support for the concept that herpes simplex virus type 1 (HSV1), when present in the brains of apolipoprotein E-ε4 carriers, is a major risk for Alzheimer's disease (AD) is increasing steadily, with over 120 publications providing direct or indirect evidence relevant to the hypothesis. No articles have contested the concept, apart from 3 published 13-18 yr ago. This review describes very recent studies on the role of HSV1 but refers also to older studies that provide background for some lesser-known related topics not covered in other recent reviews; these include the relevance of herpes simplex encephalitis and of epilepsy to AD, the action of IFN, and the possible relevance of the different types of DNA damage to AD-in particular, those caused by HSV1-and mechanisms of repair of damage. New epidemiologic data supporting previous studies on mild cognitive impairment and progression to AD are reviewed, as are those examining the relationship between total infectious burden (additive seropositivity to various microbes) and cognition/AD. The latter indicates the involvement of HSV1 and cytomegalovirus (and the necessity of taking into account any marked differences in sensitivity of antibody detection). Recent studies that provide further support for the occurrence of repeated reactivation of latent HSV1 in the brain in AD pathogenesis are also discussed.-Itzhaki, R. F. Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts. © FASEB.

  11. [Enzymatic activity of thymidine kinase of herpes simlex virus strain resistant to H-phosphonates of Acv].

    PubMed

    Gus'kova, A A; Skoblov, M Iu; Andronova, V L; Galegov, G A; Kochetkov, S N; Skoblov, Iu S

    2011-01-01

    Cloned laboratory mutants of herpes simplex virus type I resistant to acycloguanosine H-phosphonate have been investigated. For all clones were shown that mutations resulted to increasing of sensitivity to acting of sidofovir. Thymidine kinase of mutant viruses partially preserves the ability to phosphorilate thymidine, but loses the ability to phosphorilate BVDU.

  12. Herpes simplex virus clearance during purification of a recombinant adeno-associated virus serotype 1 vector.

    PubMed

    Ye, Guo-jie; Scotti, Marina M; Thomas, Darby L; Wang, Lijun; Knop, David R; Chulay, Jeffrey D

    2014-12-01

    Gene delivery vectors based on adeno-associated virus (AAV) have potential utility for treatment of many genetic disorders. Current AAV vector manufacturing methods employ helper viruses to deliver functions needed to produce replication-defective recombinant AAV (rAAV) vectors, and clearance of infectious helper virus from the drug substance is essential for ensuring the safety of rAAV-based therapies. We have developed a manufacturing method for the production of rAAV vectors using a recombinant herpes simplex virus type 1 (rHSV) complementation system in suspension baby hamster kidney cells. The manufacturing process includes three primary unit operations, detergent lysis of the cell harvest and two downstream column chromatography steps, which achieve viral clearance. These unit operations inactivate and remove HSV, including replication-competent HSV present at low levels in rHSV helper stocks. Here we report results quantifying the reduction in HSV achieved during rAAV vector purification. Clearance of HSV was at least 6.84 log10 with 1% Triton X-100, 4.34 log10 with CIM Q column chromatography, and 2.86 log10 with AVB affinity chromatography. Combined, these three orthogonal methods achieved clearance of at least 14.04 log10 of HSV. The total input quantity of rHSV in a 100-liter production batch is approximately 1.2×10(12) plaque-forming units (pfu), and after purification, the concentration of residual rHSV in the resulting drug substance of approximately 450 ml would be less than 2.42×10(-5) pfu/ml. A rAAV vector produced using this method was used in a clinical trial in which subjects receive up to 100 intramuscular injections of 1.35 ml each, which would contain a maximum of 3.27×10(-3) pfu of HSV. These results support the safety of rAAV vectors produced using our rHSV complementation method.

  13. Completely assembled virus particles detected by transmission electron microscopy in proximal and mid-axons of neurons infected with herpes simplex virus type 1, herpes simplex virus type 2 and pseudorabies virus

    SciTech Connect

    Huang Jialing Lazear, Helen M. Friedman, Harvey M.

    2011-01-05

    The morphology of alphaherpesviruses during anterograde axonal transport from the neuron cell body towards the axon terminus is controversial. Reports suggest that transport of herpes simplex virus type 1 (HSV-1) nucleocapsids and envelope proteins occurs in separate compartments and that complete virions form at varicosities or axon termini (subassembly transport model), while transport of a related alphaherpesvirus, pseudorabies virus (PRV) occurs as enveloped capsids in vesicles (assembled transport model). Transmission electron microscopy of proximal and mid-axons of primary superior cervical ganglion (SCG) neurons was used to compare anterograde axonal transport of HSV-1, HSV-2 and PRV. SCG cell bodies were infected with HSV-1 NS and 17, HSV-2 2.12 and PRV Becker. Fully assembled virus particles were detected intracellularly within vesicles in proximal and mid-axons adjacent to microtubules after infection with each virus, indicating that assembled virions are transported anterograde within axons for all three alphaherpesviruses.

  14. Electron microscope studies of temperature-sensitive mutants of herpes simplex virus type 2.

    PubMed Central

    Cabral, G A; Schaffer, P A

    1976-01-01

    Nine temperature-sensitive mutants of herpes simplex virus type 2 representing eight complementation groups were assigned to two classes as a consequence of the virion forms and virus-specific cellular alterations observed in thin sections of mutant-infected human embryonic lung cells grown at the nonpermissive temperature. Mutants in class A, one DNA- and one DNA +, failed to synthesize detectable virus particles. Mutants in class B, 4DNA- and 3DNA+, produced moderate to large numbers of empty nucleocapsids. Dense-cored nucleocapsids were not observed in thin sections of cells infected with any of the nine mutants at this temperature. Virus-specific cellular alterations consisted primarily of margination of chromating and nulcear membrane thickening and duplication. Images PMID:178905

  15. Electron microscope studies of temperature-sensitive mutants of herpes simplex virus type 2.

    PubMed

    Cabral, G A; Schaffer, P A

    1976-05-01

    Nine temperature-sensitive mutants of herpes simplex virus type 2 representing eight complementation groups were assigned to two classes as a consequence of the virion forms and virus-specific cellular alterations observed in thin sections of mutant-infected human embryonic lung cells grown at the nonpermissive temperature. Mutants in class A, one DNA- and one DNA +, failed to synthesize detectable virus particles. Mutants in class B, 4DNA- and 3DNA+, produced moderate to large numbers of empty nucleocapsids. Dense-cored nucleocapsids were not observed in thin sections of cells infected with any of the nine mutants at this temperature. Virus-specific cellular alterations consisted primarily of margination of chromating and nulcear membrane thickening and duplication.

  16. Polyhydroxylated sulfated steroids derived from 5α-cholestanes as antiviral agents against herpes simplex virus.

    PubMed

    Pujol, Carlos A; Sepúlveda, Claudia S; Richmond, Victoria; Maier, Marta S; Damonte, Elsa B

    2016-07-01

    Twelve polyhydroxylated sulfated steroids synthesized from a 5α-cholestane skeleton with different substitutions in C-2, C-3 and C-6 were evaluated for cytotoxicity and antiviral activity against herpes simplex virus (HSV) by a virus plaque reduction assay. Four compounds elicited a selective inhibitory effect against HSV. The disodium salt of 2β,3α-dihydroxy-6E-hydroximine-5α-cholestane-2,3-disulfate, named compound 7, was the most effective inhibitor of HSV-1, HSV-2 and pseudorabies virus (PrV) strains, including acyclovir-resistant variants, in human and monkey cell lines. Preliminary mechanistic studies demonstrated that compound 7 did not affect the initial steps of virus entry but inhibited a subsequent event in the infection process of HSV.

  17. Characterization of soluble glycoprotein D-mediated herpes simplex virus type 1 infection

    SciTech Connect

    Tsvitov, Marianna; Frampton, Arthur R.; Shah, Waris A.; Wendell, Steven K.; Ozuer, Ali; Kapacee, Zoher; Goins, William F.; Cohen, Justus B.; Glorioso, Joseph C. . E-mail: glorioso@pitt.edu

    2007-04-10

    Herpes simplex virus type 1 (HSV-1) entry into permissive cells involves attachment to cell-surface glycosaminoglycans (GAGs) and fusion of the virus envelope with the cell membrane triggered by the binding of glycoprotein D (gD) to cognate receptors. In this study, we characterized the observation that soluble forms of the gD ectodomain (sgD) can mediate entry of gD-deficient HSV-1. We examined the efficiency and receptor specificity of this activity and used sequential incubation protocols to determine the order and stability of the initial interactions required for entry. Surprisingly, virus binding to GAGs did not increase the efficiency of sgD-mediated entry and gD-deficient virus was capable of attaching to GAG-deficient cells in the absence of sgD. These observations suggested a novel binding interaction that may play a role in normal HSV infection.

  18. Rapid diagnosis of herpetic encephalitis in children by PCR-microarray technology for simultaneous detection of seven human herpes viruses.

    PubMed

    Shi, Jianrong; Wu, Yidong; Cai, Meiting; Shang, Shiqiang

    2010-04-01

    The aim of the study was to evaluate retrospectively the usefulness of polymerase chain reaction (PCR)-microarray technology, which can simultaneously detect seven human herpes viruses for rapid and accurate diagnosis of herpetic encephalitis in children. We simultaneously amplified herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2); varicella-zoster virus; Epstein-Barr virus (EBV); cytomegalovirus (CMV); and human herpes virus 6 (HHV-6A and HHV-6B) by multiplex PCR, and genotyped by DNA microarray technology. The multiplex primers and oligonucleotide probes were designed and synthesized based on the highly conserved regions of the DNA polymerase gene in human herpes viruses. Two hundred ninety cerebrospinal fluid (CSF) specimens from children with clinical suspicion of viral encephalitis were screened by PCR-microarray technology. The results were compared with those of TaqMan PCR kits of common herpes virus. The PCR-microarray technology could detect as few as 10 copies of viral loads. There was no nonspecific hybridizing signal between probes and no cross-reaction to DNA extracted from the pathogens we used. Of 290 cases, 11 were tested positive by PCR-microarray technology. Among them, three were positive for HSV-1, two were positive for HSV-2, one was positive for EBV, two were positive for CMV, two were positive for HHV-6A, one was positive for HHV-6B, and one showed mixed infection of HSV-2 and CMV, and the positive rate was 3.8%. Compared with the results of TaqMan PCR, the sensitivity of PCR-microarray technology was 91.7%, the specificity was 100%, and the index of accurate diagnosis was 0.917. None of the 30 control CSF specimens was tested positive in both methods. Our study suggests that the simultaneous detection of seven human herpes viruses by PCR-microarray technology is the method of choice for rapid, accurate, and specific etiological diagnosis of herpetic encephalitis in children.

  19. [Herpes simplex virus type 1-induced rising dbl quote, left (low)tumor" in the nasal vestibule. The problem of resistance development of herpes simplex in a patient with chronic lymphatic B-cell leukemia].

    PubMed

    Althof, F; Mechtersheimer, M; Richter, M; Dietz, A

    2000-02-01

    Herpes simplex viruses are known to be among the most common disease-causing microorganisms. Their prevalence can exceed 90% depending on the socioeconomic status of the population. Since the number of immunocompromised patients has increased because of the increased incidence in the acquired immunodeficiency syndrome and an increase in organ transplantation, herpes virus infection may have a greater clinical significance. While treatment of otherwise healthy individuals will not usually cause any clinical problems herpes infection in an immunocompromised patient can have severe consequences. Additionally, development of viral resistance can be observed that may require alternative drugs in treatment. We present a case history of a man with a B-cell chronic lymphocytic leukemia that was associated with a very unusual herpes simplex virus infection in the nasal vestibule. Possible causes for the development of resistance in herpes infections and the use of famciclovir and forscarnet as two therapeutic alternatives to aciclovir are discussed.

  20. 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

    PubMed Central

    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

  1. 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.

    PubMed

    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.

  2. Human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient presenting with relapsing and remitting hyponatraemia.

    PubMed

    Sasaki, Hiroaki; Maeda, Takuya; Hara, Yu; Osa, Morichika; Imai, Kazuo; Moriguchi, Kota; Mikita, Kei; Fujikura, Yuji; Kaida, Kenichi; Kawana, Akihiko

    2015-10-01

    We report a case of human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient with hyponatraemia. A 65-year-old man was admitted with relapsing and remitting fever, scattered skin eruptions and hepatosplenomegaly following combination antiretroviral therapy for his HIV infection. Based on histopathological findings, he was diagnosed as having human herpes virus-8-associated multicentric Castleman's disease and was treated with four-weekly infusions of rituximab. Prior to receiving chemotherapy, we observed several suspected biomarkers of disease activity, positive correlations between plasma human herpes virus-8 viral load and the levels of plasma interleukin-6, C-reactive protein and soluble interleukin-2 receptor, and negative correlations between platelet count, albumin levels and especially serum sodium levels. We hypothesize that non-osmotic release of plasma antidiuretic hormone is a cause of hyponatraemia in human herpes virus-8-associated multicentric Castleman's disease and that relapsing and remitting hyponatraemia could be correlated with plasma human herpes virus-8 viral load.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Detection of aerosolized varicella-zoster virus DNA in patients with localized herpes zoster.

    PubMed

    Suzuki, Kayoko; Yoshikawa, Tetsushi; Tomitaka, Akiko; Matsunaga, Kayoko; Asano, Yoshizo

    2004-03-15

    We examined the excretion of varicella zoster virus (VZV) in hospitalized patients with herpes zoster localized to the thoracic region whose skin lesions were covered with either hydrocolloid dressing agents (hydrocolloid group) or conventional gauze bandages (gauze group). The presence of VZV DNA in swab samples from lesion coverings, the throat, and filters of air purifiers was examined by use of a sensitive polymerase chain reaction assay. For the hydrocolloid group, VZV was detected in none of the samples from lesion coverings or air purifier filters; for the gauze group, VZV DNA was detected in samples from gauze coverings and air purifier filters for all 6 patients. VZV DNA was detected less frequently in throat samples from patients in the hydrocolloid group than in those from patients in the gauze group. The results of the present study suggest that hydrocolloid dressing agents prevent excretion of aerosolized VZV DNA from skin lesions of patients with localized herpes zoster.

  5. Nuclear Sensing of Viral DNA, Epigenetic Regulation of Herpes Simplex Virus Infection, and Innate Immunity

    PubMed Central

    Knipe, David M.

    2015-01-01

    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. Herpes 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. PMID:25742715

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

    PubMed Central

    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. Images PMID:2827006

  7. A Complex Role of Herpes Viruses in the Disease Process of Multiple Sclerosis

    PubMed Central

    Wuest, Simone C.; Mexhitaj, Ina; Chai, Noo Ri; Romm, Elena; Scheffel, Joerg; Xu, Biying; Lane, Kelly; Wu, Tianxia; Bielekova, Bibiana

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS). Neither the antigenic target(s) nor the cell population(s) responsible for CNS tissue destruction in MS have been fully defined. The objective of this study was to simultaneously determine the antigen (Ag)-specificity and phenotype of un-manipulated intrathecal CD4+ and CD8+ T cells of patients with relapsing-remitting and progressive MS compared to subjects with other inflammatory neurological diseases. We applied a novel Ag-recognition assay based on co-cultures of freshly obtained cerebrospinal fluid T cells and autologous dendritic cells pre-loaded with complex candidate Ag's. We observed comparably low T cell responses to complex auto-Ag's including human myelin, brain homogenate, and cell lysates of apoptotically modified oligodendroglial and neuronal cells in all cohorts and both compartments. Conversely, we detected a strong intrathecal enrichment of Epstein-Barr virus- and human herpes virus 6-specific (but not cytomegalovirus-specific) reactivities of the Th1-phenotype throughout all patients. Qualitatively, the intrathecal enrichment of herpes virus reactivities was more pronounced in MS patients. This enrichment was completely reversed by long-term treatment with the IL-2 modulating antibody daclizumab, which strongly inhibits MS disease activity. Finally, we observed a striking discrepancy between diminished intrathecal T cell proliferation and enhanced cytokine production of herpes virus-specific T cells among progressive MS patients, consistent with the phenotype of terminally differentiated cells. The data suggest that intrathecal administration of novel therapeutic agents targeting immune cells outside of the proliferation cycle may be necessary to effectively eliminate intrathecal inflammation in progressive MS. PMID:25148387

  8. Characterization of herpes virus entry mediator as a factor linked to obesity.

    PubMed

    Bassols, Judit; Moreno, Jose M; Ortega, Francisco; Ricart, Wifredo; Fernandez-Real, Jose M

    2010-02-01

    Herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor (TNF) receptor superfamily (TNFRSF14), which serves as a receptor for herpes viruses and cytokines such as lymphotoxin-alpha (LT-alpha) and LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpes virus entry on T cells). We aimed to explore the associations of HVEM with human obesity. HVEM gene expression and protein levels were studied in total adipose tissue and in their fractions (isolated adipocytes and stromovascular cells (SVCs)) obtained from 81 subjects during elective surgical procedures. HVEM -241GA and -14AG gene polymorphisms were also studied and associated with obesity measures in 840 subjects. Visceral adipose tissue had significantly higher expression of HVEM than subcutaneous adipose tissue (P < 0.0001). Obese patients had significantly higher subcutaneous HVEM gene expression (P = 0.03) and protein levels (P = 0.01) than lean subjects. HVEM gene expression and protein levels were found in both isolated adipocytes and SVCs. These findings were confirmed in primary cultures from human preadipocytes, in which a significant increase in HVEM was observed during the differentiation process. HVEM -241GA and -14AG gene polymorphisms were associated with obesity, diastolic pressure, several inflammatory parameters (C-reactive protein and interleukin 18 (IL-18)), and circulating LIGHT concentrations. A sample of men with the G241A gene polymorphism also showed an increased serum titer of IgG antiherpes virus 1. These results provide evidences of an existing relationship between HVEM and obesity, which suggest that this TNF superfamily receptor could be involved in the pathogenesis of obesity and inflammation-related activity.

  9. A complex role of herpes viruses in the disease process of multiple sclerosis.

    PubMed

    Wuest, Simone C; Mexhitaj, Ina; Chai, Noo Ri; Romm, Elena; Scheffel, Joerg; Xu, Biying; Lane, Kelly; Wu, Tianxia; Bielekova, Bibiana

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS). Neither the antigenic target(s) nor the cell population(s) responsible for CNS tissue destruction in MS have been fully defined. The objective of this study was to simultaneously determine the antigen (Ag)-specificity and phenotype of un-manipulated intrathecal CD4+ and CD8+ T cells of patients with relapsing-remitting and progressive MS compared to subjects with other inflammatory neurological diseases. We applied a novel Ag-recognition assay based on co-cultures of freshly obtained cerebrospinal fluid T cells and autologous dendritic cells pre-loaded with complex candidate Ag's. We observed comparably low T cell responses to complex auto-Ag's including human myelin, brain homogenate, and cell lysates of apoptotically modified oligodendroglial and neuronal cells in all cohorts and both compartments. Conversely, we detected a strong intrathecal enrichment of Epstein-Barr virus- and human herpes virus 6-specific (but not cytomegalovirus-specific) reactivities of the Th1-phenotype throughout all patients. Qualitatively, the intrathecal enrichment of herpes virus reactivities was more pronounced in MS patients. This enrichment was completely reversed by long-term treatment with the IL-2 modulating antibody daclizumab, which strongly inhibits MS disease activity. Finally, we observed a striking discrepancy between diminished intrathecal T cell proliferation and enhanced cytokine production of herpes virus-specific T cells among progressive MS patients, consistent with the phenotype of terminally differentiated cells. The data suggest that intrathecal administration of novel therapeutic agents targeting immune cells outside of the proliferation cycle may be necessary to effectively eliminate intrathecal inflammation in progressive MS.

  10. Prime-boost immunization using DNA vaccine and recombinant Orf virus protects pigs against Pseudorabies virus (Herpes suid 1).

    PubMed

    Dory, Daniel; Fischer, Timo; Béven, Véronique; Cariolet, Roland; Rziha, Hanns-Joachim; Jestin, André

    2006-09-11

    The present study demonstrates the protective potential of a novel prime-boost vaccination strategy of pigs against lethal Pseudorabies virus (PRV; Herpes suid 1) infection. Animals were primed with Sindbis virus-derived plasmids that express viral glycoproteins gC and gD (gC- and gD-pSIN) and subsequently booster immunized with Orf virus (ORFV; Parapoxvirus) recombinants expressing gC and gD (D1701-VrVgC and -VrVgD). The prime-boost vaccination induced strong humoral and cellular-like PRV-specific immune responses. All prime-boost vaccinated pigs survived the lethal challenge infection without PRV-specific clinical symptoms and presented excellent body weight loss attenuation. Most notably, nasal shedding of challenge virus was reduced by more than about 3log(10), clearly reducing the risk of infection of non-immunized pigs.

  11. Vaccine potential of a herpes simplex virus type 1 mutant with an essential glycoprotein deleted.

    PubMed Central

    Farrell, H E; McLean, C S; Harley, C; Efstathiou, S; Inglis, S; Minson, A C

    1994-01-01

    Several approaches to the production of vaccines to human herpesviruses have been proposed. Subunit vaccines, subunits delivered by live vectors, and rationally attenuated vaccines have all been shown to be efficacious in animal models but suffer from uncertainties as to the roles of individual genes involved in pathogenesis and the most relevant components of the immune response required for protection in humans and the target antigens involved. With these problems in mind, we examined the vaccine potential of a fully disabled herpes simplex virus type 1 mutant that is capable of only a single round of replication, since a virus of this type should induce the full spectrum of immune responses but has no pathogenic potential. A virus has been described which lacks essential glycoprotein H (gH) and can be propagated in a cell line which supplies gH in trans (A. Forrester, H. Farrell, G. Wilkinson, J. Kaye, N. Davis-Poynter, and T. Minson, J. Virol. 66:341-348, 1992). Infection of normal cells with this mutant is indistinguishable from a wild-type infection, except that the resulting progeny are gH negative and noninfectious: the virus is self-limiting. Infection of mice by the ear pinna route was similarly self-limiting in that input infectivity decreased rapidly at the inoculation site and no infectivity was detected in sensory ganglia. Animals given a wide range of doses of the gH-negative mutant produced both humoral and T-cell responses to herpes simplex virus type 1 and proved solidly resistant to challenge with a high dose of wild-type virus. The gH-negative mutant is presumably capable of establishing a latent infection, but since no infectious virus was detected in numerous attempts to reactivate the mutant, the risk of a pathogenic outcome is minimal. Images PMID:8289395

  12. Recent advances in the chemotherapy of herpes virus infections.

    PubMed

    Eşanu, V

    1981-01-01

    The main categories of antiherpes agents presently used in chemotherapy area reviewed according to the phase of virus replication affected : 1) virus adsorption (adamantane, nonionic surfactants) ; 2) eclipse (interferon) ; 3) virion maturation (nucleoside and nucleotide analogues and phosphonic acid derivatives). Mention is also made of other compounds--different synthetic organic derivatives, photodynamic dyes, metal ions, boric acid, hormones, antibiotics, other natural products (extracts from marine algae, propolis, garlic)--with promising antiviral properties. The difficulties and prospects of viral chemotherapy research are briefly discussed.

  13. Isolation of virus from brain after immunosuppression of mice with latent herpes simplex

    NASA Astrophysics Data System (ADS)

    Kastrukoff, Lorne; Long, Carol; Doherty, Peter C.; Wroblewska, Zofia; Koprowski, Hilary

    1981-06-01

    Herpes simplex virus (HSV) is usually present in a latent form in the trigeminal ganglion of man1-3. Various stress factors may induce virus reactivation, which is manifest by a lip lesion (innervated from the trigeminal ganglion) and the production of infectious virus. The considerable experimental efforts to define the conditions that lead to the reactivation of latent HSV have concentrated on isolating virus either from the original extraneural site of virus inoculation, or from cell-free homogenates of sensory ganglia from latently infected animals4-15. Recent DNA hybridization experiments resulted in the demonstration of the presence of HSV genomes in the brain tissue of both latently infected mice, and of humans who showed no clinical symptoms of HSV (ref. 16 and N. Fraser, personal communication). This led us to consider the possibility that HSV may be present in brain tissue as the result of either reactivation of the virus in brain cells or the passage of reactivated virus from trigeminal ganglia through the brain stem to the brain. The presence of infectious HSV in brain tissue has not previously been demonstrated; yet this could be a factor in chronic, relapsing neurological diseases such as multiple sclerosis. We have now shown experimentally that mice carrying latent HSV in their trigeminal ganglia may, following massive immunosuppression, express infectious virus in the central nervous system (CNS).

  14. Adaptation of a retrovirus as a eucaryotic vector transmitting the herpes simplex virus thymidine kinase gene

    SciTech Connect

    Tabin, C.J.; Hoffman, J.W.; Goff, S.P.; Weinberg, R.A.

    1982-04-01

    The authors investigated the feasibility of using retroviruses as vectors for transferring DNA sequences into animal cells. The thymidine kinase (tk) gene of herpes simplex virus was chosen as a convenient model. The internal BamHI fragments of a DNA clone of Moloney leukemia virus (MLV) were replaced with a purified BamHI DNA segment containing the tk gene. Chimeric genomes were created carrying the tk insert on both orientations relative to the MLV sequence. Each was transfected into TK/sup -/ cells along with MLV helper virus, and TK/sup +/ colonies were obtained by selection in the presence of hypoxanthine, aminopterin, and thymidine (HAT). Virus collected from TK/sup +/-transformed, MLV producer cells passed the TK/sup +/ phenotype to TK/sup -/ cells. Nonproducer cells were isolated, and TK/sup +/ transducing virus was subsequently rescued from them. The chimeric virus showed single-hit kinetics in infections. Virion and cellular RNA and cellular DNA from infected cells were all shown to contain sequences which hybridized to both MLV- and tk-specific probes. The sizes of these sequences were consistent with those predicted for the chimeric virus. In all respects studied, the chimeric MLV-tk virus behaved like known replication-defective retroviruses. These experiments suggest great general applicability of retroviruses as eucaryotic vectors.

  15. The Role of Plasmacytoid Dendritic Cells in Innate and Adaptive Immune Responses against Alpha Herpes Virus Infections

    PubMed Central

    Schuster, Philipp; Boscheinen, Jan Bernardin; Tennert, Karin; Schmidt, Barbara

    2011-01-01

    In 1999, two independent groups identified plasmacytoid dendritic cells (PDC) as major type I interferon- (IFN-) producing cells in the blood. Since then, evidence is accumulating that PDC are a multifunctional cell population effectively coordinating innate and adaptive immune responses. This paper focuses on the role of different immune cells and their interactions in the surveillance of alpha herpes virus infections, summarizes current knowledge on PDC surface receptors and their role in direct cell-cell contacts, and develops a risk factor model for the clinical implications of herpes simplex and varicella zoster virus reactivation. Data from studies involving knockout mice and cell-depletion experiments as well as human studies converge into a “spider web”, in which the direct and indirect crosstalk between many cell populations tightly controls acute, latent, and recurrent alpha herpes virus infections. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses more extensively than previously thought. PMID:22312349

  16. Characterization of heterosubunit complexes formed by the R1 and R2 subunits of herpes simplex virus 1 and equine herpes virus 4 ribonucleotide reductase.

    PubMed

    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.

  17. Epidemiology and clinical characteristics of infants with human parechovirus or human herpes virus-6 detected in cerebrospinal fluid tested for enterovirus or herpes simplex virus.

    PubMed

    Messacar, Kevin; Breazeale, Garrett; Wei, Qi; Robinson, Christine C; Dominguez, Samuel R

    2015-05-01

    Human parechovirus (HPeV) and human herpes virus-6 (HHV-6) are acquired commonly in infancy and associated with central nervous system infection. The prevalence of HPeV and HHV-6 in the cerebrospinal fluid (CSF) of infants tested for enterovirus (EV) and herpes-simplex virus (HSV) is unknown. All stored CSF samples from EV or HSV testing in infants less than 6 months of age at Children's Hospital Colorado between January 1, 2010 and December 31, 2011 were tested for HPeV, HHV-6, EV, and HSV by PCR. Clinical characteristics and epidemiological data were collected using retrospective electronic chart review. Of 239 infants tested, 29 cases of EV (12.1%), 7 cases of HPeV (2.9%), 5 cases of HHV-6 (2.1%), and 5 cases of HSV (2.1%) were identified with no bacterial co-infections. HPeV cases occurred between July and October in infants with median age of 24 days. Infants with HPeV had a median maximum temperature of 39 °C, median fever duration of 3 days and median peripheral white blood cell count of 5.2 × 10(3)/μL. HHV-6 cases occurred in infants with median age of 61 days without seasonality. Five percent of infants less than 6 months of age undergoing testing for EV or HSV have HPeV or HHV-6 in the CSF. Targeting testing of HPeV towards febrile infants less than 2 months of age with leukopenia in the late summer to early fall, and HHV-6 towards older infants may increase diagnostic yield. The clinical and fiscal impact of testing infants for HPeV and HHV-6 needs to be determined.

  18. Gene transfer into hepatocytes mediated by herpes simplex virus-Epstein-Barr virus hybrid amplicons.

    PubMed

    Müller, Lars; Saydam, Okay; Saeki, Yoshinaga; Heid, Irma; Fraefel, Cornel

    2005-01-01

    Gene transfer into hepatocytes is highly desirable for the long-term goal of replacing deficient proteins and correcting metabolic disorders. Vectors based on herpes simplex virus type-1 (HSV-1) have been demonstrated to mediate efficient gene transfer into hepatocytes both in vitro and in vivo. Large transgene capacity and extrachromosomal persistence make HSV-1/EBV hybrid amplicon vectors an attractive candidate for hepatic gene replacement therapy. To assess liver-directed gene transfer, we constructed (i) a conventional HSV-1 amplicon vector encoding a secreted reporter protein (secreted alkaline phosphatase, SEAP) under the control of the HSV-1 immediate-early 4/5 promoter; (ii) a HSV-1 amplicon encoding SEAP under the control of the artificial CAG promoter (the chicken beta-actin promoter and cytomegalovirus (CMV) immediate-early enhancer); and (iii) a HSV-1/EBV hybrid amplicon, also encoding SEAP under the control of the CAG promoter. While all three vector constructs yielded high SEAP concentrations in vitro and in vivo, use of HSV-1/EBV hybrid amplicon vectors significantly prolonged the duration of gene expression. Using conventional amplicon vectors in cultured hepatocytes, SEAP was detected for two weeks, whereas SEAP was detected for at least six weeks when HSV-1/EBV amplicons were used. Intraparenchymal injection into the liver of SICD mice yielded high (up to 77 ng of SEAP per milliliter serum) and sustained (greater than three weeks) expression of SEAP. Serum transaminases (ALT/AST) were measured at different time points to monitor for hepatocellular damage. While initially elevated four times above baseline, the transaminase levels returned to normal after three to seven days. These results demonstrate the usefulness of HSV-1-based amplicons and SEAP for the evaluation of gene replacement strategies in the liver.

  19. Development of a selective biopharmaceutical from Herpes simplex virus type 1 glycoproteins E and I for blocking antibody mediated neutralization of oncolytic viruses.

    PubMed

    Bucurescu, Septimiu

    2010-12-01

    Future cancer therapies will be molecular cures. They will correct, block or destroy cancer cells by targeting molecular changes that lead to carcinogenesis. Destroying cancer cells can be done using oncolytic viruses. By blocking antibody mediated neutralization of oncolytic viruses, Herpes simplex virus type 1 glycoproteins E and I could be used in the adjuvant treatment of cancer for improving the chances of oncolytic viruses to kill cancer cells in vivo.

  20. Isolation and preliminary characterization of herpes simplex virus 1 primary enveloped virions from the perinuclear space.

    PubMed

    Padula, Maryn E; Sydnor, Mariam L; Wilson, Duncan W

    2009-05-01

    Herpes simplex virus 1 (HSV-1) nucleocapsids exit the nucleus by budding into the inner nuclear membrane, where they exist briefly as primary enveloped virions. These virus particles subsequently fuse their envelopes with the outer nuclear membrane, permitting nucleocapsids to then enter the cytoplasm and complete assembly. We have developed a method to isolate primary enveloped virions from HSV-1-infected cells and subjected the primary enveloped virion preparation to MALDI-MS/MS (matrix-assisted laser desorption ionization-tandem mass spectrometry) analyses. We identified most capsid proteins, a tegument protein (VP22), a glycoprotein (gD), and a cellular protein (annexin A2) in the primary enveloped virion preparation. We determined that annexin A2 does not play an essential role in infection under our experimental conditions. Elucidating the structure and biochemical properties of this unique virus assembly intermediate will provide new insights into HSV-1 biology.

  1. In vivo reactivation of herpes simplex virus in rabbit trigeminal ganglia: electrode model.

    PubMed Central

    Green, M T; Rosborough, J P; Dunkel, E C

    1981-01-01

    The rabbit provides an excellent model for the study of ocular herpes because herpetic keratitis in the rabbit eye resembles human disease in its clinical features and in its propensity for spontaneous recurrence. This paper presents a method for the electrical induction of multiple episodes of in vivo reactivation of latent HSV-1 infection with peripheral shedding of virus. Physiological levels of current delivered via an electrode implanted over the trigeminal ganglion of latently infected animals has enabled us to modify and synchronize virus shedding in preocular tear film and to cause multiple episodes of reactivation in a single animal. For this reason, the model is well suited for antiviral efficacy testing and provides an excellent opportunity for investigation of virus-host cell interactions in latent and recurring herpetic disease. Images PMID:6271686

  2. Systems Analysis of Protein Fatty Acylation in Herpes Simplex Virus-Infected Cells Using Chemical Proteomics

    PubMed Central

    Serwa, Remigiusz A.; Abaitua, Fernando; Krause, Eberhard; Tate, Edward W.; O’Hare, Peter

    2015-01-01

    Summary Protein fatty acylation regulates diverse aspects of cellular function and organization and plays a key role in host immune responses to infection. Acylation also modulates the function and localization of virus-encoded proteins. Here, we employ chemical proteomics tools, bio-orthogonal probes, and capture reagents to study myristoylation and palmitoylation during infection with herpes simplex virus (HSV). Using in-gel fluorescence imaging and quantitative mass spectrometry, we demonstrate a generalized reduction in myristoylation of host proteins, whereas palmitoylation of host proteins, including regulators of interferon and tetraspanin family proteins, was selectively repressed. Furthermore, we found that a significant fraction of the viral proteome undergoes palmitoylation; we identified a number of virus membrane glycoproteins, structural proteins, and kinases. Taken together, our results provide broad oversight of protein acylation during HSV infection, a roadmap for similar analysis in other systems, and a resource with which to pursue specific analysis of systems and functions. PMID:26256475

  3. Structure of the transporter associated with antigen processing trapped by herpes simplex virus.

    PubMed

    Oldham, Michael L; Grigorieff, Nikolaus; Chen, Jue

    2016-12-09

    The transporter associated with antigen processing (TAP) is an ATP-binding cassette (ABC) transporter essential to cellular immunity against viral infection. Some persistent viruses have evolved strategies to inhibit TAP so that they may go undetected by the immune system. The herpes simplex virus for example evades immune surveillance by blocking peptide transport with a small viral protein ICP47. In this study, we determined the structure of human TAP bound to ICP47 by electron cryo-microscopy (cryo-EM) to 4.0 Å. The structure shows that ICP47 traps TAP in an inactive conformation distinct from the normal transport cycle. The specificity and potency of ICP47 inhibition result from contacts between the tip of the helical hairpin and the apex of the transmembrane cavity. This work provides a clear molecular description of immune evasion by a persistent virus. It also establishes the molecular structure of TAP to facilitate mechanistic studies of the antigen presentation process.

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

    SciTech Connect

    Park, N.H.; Dokko, H.; Li, S.L.; Cherrick, H.M. )

    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.

  5. Age-specific incidence of neutralization antibodies of Herpes simplex virus.

    PubMed Central

    Terzin, A. L.; Masic, M. G.

    1976-01-01

    Sera of 1255 individuals from Novi Sad, varying in age from less than 1 month to 69 years, have been tested for neutralization antibodies to Herpes implex virus type 1. The eight newborns tested and 97% of the 507 adults were positive, with titres ranging from 1/4 to 1/256. The titres in newborns were significantly lower than the titres in adults. After birth the maternal antibodies declined rapidly and 94% of infants at the age of greater than 6 months and less than 2 years were negative. After the first year infants in Novi Sad start to acquire herpes-neutralizing antibodies actively, reaching a 50% incidence of positives between the 2nd and 3rd year of age. Age-specific incidence rates of herpes positives found in Novi Sad have been compared with those reported from Edinburgh, Freiburg i. Br. and Louisiana. Possible influences of several circumstances upon the incidence rate of positives detected by the neutralization test are discussed. PMID:185287

  6. The alpha-herpesviridae in dermatology : Herpes simplex virus types I and II.

    PubMed

    El Hayderi, L; Rübben, A; Nikkels, A F

    2017-02-14

    This review on herpes simplex virus type I and type II (HSV‑I, HSV‑II) summarizes recent developments in clinical manifestations and treatment interventions for primary and recurrent orolabial and genital herpes, as well as those regarding vaccination issues. Among the clinical presentations, the relationship between pyogenic granuloma and chronic HSV‑I infection; HSV-related folliculitis; verrucous HSV‑I and HSV‑II lesions; the role of recurrent HSV‑I infection in burning mouth syndrome; HSV‑I and HSV‑II infection of the periareolar area; zosteriform HSV; the "knife-cut sign"; and the preferential colonization and infection of preexisting dermatoses by HSV‑I or HSV‑II are discussed. The usual antiviral treatment regimens for primary and recurrent orolabial and genital herpes are compared to short-term and one-day treatment options. New anti-HSV‑I and anti-HSV‑II agents include amenavir, pritelivir, brincidofovir, valomaciclovir, and FV-100. Therapeutic or preventive vaccination against HSV‑I and HSV‑II infections still remains a highly desirable treatment aim, which, unfortunately, has no clinically relevant applications to date.

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

    PubMed Central

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

    PubMed

    LeGoff, Jérôme; Péré, Hélène; Bélec, Laurent

    2014-05-12

    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.

  9. Molecular diagnostics and newborns at risk for genital herpes simplex virus.

    PubMed

    Chua, Caroline; Arnolds, Marin; Niklas, Victoria

    2015-05-01

    Herpes simplex virus (HSV) infection in the newborn carries a high mortality rate and can result in lifelong neurologic impairment. The severity of HSV infection in the newborn has always dictated conservative management when prodromal symptoms or active genital lesions (or those suggestive of genital herpes) are present during labor and delivery. The risk of intrapartum infection, however, is related to the presence or absence of maternal immunity (neutralizing antibody) to HSV. The most significant risk of transmission is in first-episode primary infections with active lesions at delivery. Recent recommendations from the American Academy of Pediatrics Committees on Infectious Diseases and the Fetus and Newborn use rapid serologic and virologic screening in the management of asymptomatic infants born to mothers with active genital herpes. The revised guidelines highlight infants at greatest risk for HSV disease but do not apply to asymptomatic infants born to mothers with a history of HSV but no genital lesions at delivery. The current guidelines also stipulate that maternal serologic screening and molecular assays for HSV in newborn blood and cerebrospinal fluid must be available and reported in a timely fashion.

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

    PubMed

    Tang, Ka-Wei; Norberg, Peter; Holmudden, Martin; Elias, Per; Liljeqvist, Jan-Åke

    2014-01-01

    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.

  11. Rad51 and Rad52 Are Involved in Homologous Recombination of Replicating Herpes Simplex Virus DNA

    PubMed Central

    Tang, Ka-Wei; Norberg, Peter; Holmudden, Martin; Elias, Per; Liljeqvist, Jan-Åke

    2014-01-01

    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. PMID:25365323

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

    NASA Astrophysics Data System (ADS)

    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.

  13. A herpes-like virus in king crabs: Characterization and transmission under laboratory conditions.

    PubMed

    Ryazanova, T V; Eliseikina, M G; Kalabekov, I M; Odintsova, N A

    2015-05-01

    A herpes-like virus was found infecting the antennal gland and bladder epithelium in the blue king crab Paralithodes platypus from the eastern area of the Sea of Okhotsk. Electron microscopic analysis of antennal gland samples from blue king crabs with histologically confirmed signs of disease revealed virus particles, which were mostly hexagonal in shape and located primarily in the nucleus; these particles were rarely observed in the cytoplasm of infected cells. Most virus particles ranged in size from 115 to 125nm. Hemocytes of the red king crab Paralithodes camtschaticus in cell culture could be experimentally infected with virus from thawed antennal gland samples of the blue king crabs with histologically confirmed signs of viral infection. Clear signs of infection were observed in hemocyte cultures at 3-4days post-inoculation as small foci of highly vacuolated formations. These formations included several nuclei and were surrounded by a halo of small cytoplasmic bubbles containing actin and tubulin. As demonstrated by electron microscopic studies, no virus-like particles were found in the cells 1day post-inoculation, but particles become abundant at 7days post-inoculation. We developed a consensus primer PCR method for amplification of a region of the herpesviral DNA-directed DNA polymerase. Primers were designed to target sequences encoding highly conserved amino acid motifs covering a region of approximately 800bp. Thus, macroscopic, histological and ultra-structural examinations of blue king crabs infected with a virus and the molecular identification of the pathogen revealed the presence of herpesviruses. The frequency of the herpes-like viral infection in natural populations of blue king crabs in the Sea of Okhotsk ranged from 0% to 3% in different years. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Helicase primase: targeting the Achilles heel of herpes simplex viruses.

    PubMed

    Kleymann, Gerald

    2004-05-01

    The majority of the population is infected by several herpesviruses. Once these infections are established the viruses persist for life. Therefore, current therapy may at best reduce symptoms but does not cure the infection. Moreover, the only classes of compounds licensed for systemic treatment of disease are nucleoside, nucleotide and pyrophosphate analogues; all of these ultimately target the herpesvirus DNA polymerase. A vaccine against varicella zoster virus (VZV) is available, but so far no effective vaccines against other human herpesviruses have been launched. At the same time, rising resistance to current medication, especially in the immunocompromised patient population, is a concern. For these reasons, there is an urgent need for new treatment options. Recently, some promising new drugs have been discovered; one of these compounds, developed at Bayer HealthCare under the name BAY 57-1293, is a potent HSV helicase primase inhibitor.

  15. Equine herpes virus 2 infection in horse populations in Poland.

    PubMed

    Ruszczyk, A; Cywinska, A; Banbura, M W

    2004-01-01

    The prevalence of Equine herpesvirus 2 (EHV-2) infections in the horse populations in Poland was investigated. Peripheral blood leukocytes (PBLs) of 139 horses were tested. The animals were divided into four groups: clinically healthy horses, horses suffering from respiratory disorders, mares with a recent abortion and horses with diagnosed ataxia. Thirty-four virus isolates were obtained from leukocytes of the tested animals by cocultivation with equine dermal cells and were identified as EHV-2 by PCR using primers for the gB gene of EHV-2 and/or primers for the sequence located upstream of the gene homologous to the equine interleukin 10 (IL-10) gene. These results indicate that EHV-2 is prevalent in horse populations in Poland. As the virus was most frequently isolated from horses with respiratory disorders its etiological importance may be considered.

  16. New modified 2-aminobenzimidazole nucleosides: Synthesis and evaluation of their activity against herpes simplex virus type 1.

    PubMed

    Kharitonova, Maria I; Denisova, Alexandra O; Andronova, Valeria L; Kayushin, Alexei L; Konstantinova, Irina D; Kotovskaya, Svetlana K; Galegov, Georgiy A; Charushin, Valery N; Miroshnikov, Anatoly I

    2017-06-01

    Using the enzymatic transglycosylation reaction β-d-ribo- and 2'-deoxyribofuranosides of 2-amino-5,6-difluorobenzimidazole nucleosides have been synthesized. 2-Amino-5,6-difluoro-benzimidazole riboside proved to exhibit a selective antiviral activity (selectivity index >32) against a wild strain of the herpes simplex virus type 1, as well as towards virus strains that are resistant to acyclovir, cidofovir, and foscarnet. We believe that this compound might be used for treatment of herpes infections in those cases, when acyclovir is not efficient. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. The first identified nucleocytoplasmic shuttling herpesviral capsid protein: herpes simplex virus type 1 VP19C.

    PubMed

    Zhao, Lei; Zheng, Chunfu

    2012-01-01

    VP19C is a structural protein of herpes simplex virus type 1 viral particle, which is essential for assembly of the capsid. In this study, a nuclear export signal (NES) of VP19C is for the first time identified and mapped to amino acid residues 342 to 351. Furthermore, VP19C is demonstrated to shuttle between the nucleus and the cytoplasm through the NES in a chromosomal region maintenance 1 (CRM1)-dependent manner involving RanGTP hydrolysis. This makes VP19C the first herpesviral capsid protein with nucleocytoplasmic shuttling property and adds it to the list of HSV-1 nucleocytoplasmic shuttling proteins.

  18. [Human herpes virus 6 infection in an inmunocompetent patient with carbamazepine-induced DRESS syndrome].

    PubMed

    Álvarez, Sergio; Delama, Ignacio; Navajas-Galimany, Lucas; Eymin, Gonzalo; Ceballos, M Elena; Andino-Navarrete, Romina

    2016-06-01

    DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is an adverse life-threatening drug reaction characterized by a polymorphous rash associated with fever, lymphadenopathy and multiorgan involvement with eosinophilia. We present the case of an immunocompetent man with DRESS syndrome secondary to carbamazepine, that developed concomitantly meningoencephalitis caused by human herpes virus 6 (HHV-6), and a review of literature. The pathogenic role of HHV-6 in DRESS syndrome remains controversial. Given the diagnostic and possibly prognostic significance of HHV-6, the screening seems to be a good measure to use in the clinical management of these patients.

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

    PubMed

    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.

  20. Latent Herpes Simplex Virus 1 Infection Does Not Induce Apoptosis in Human Trigeminal Ganglia

    PubMed Central

    Lindemann, Anja; Sinicina, Inga; Strupp, Michael; Brandt, Thomas; Hüfner, Katharina

    2015-01-01

    Herpes simplex virus 1 (HSV-1) can establish lifelong latency in human trigeminal ganglia. Latently infected ganglia contain CD8+ T cells, which secrete granzyme B and are thus capable of inducing neuronal apoptosis. Using immunohistochemistry and single-cell reverse transcription-quantitative PCR (RT-qPCR), higher frequency and transcript levels of caspase-3 were found in HSV-1-negative compared to HSV-1-positive ganglia and neurons, respectively. No terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-positive neurons were detected. The infiltrating T cells do not induce apoptosis in latently infected neurons. PMID:25762734

  1. Incident Herpes Simplex Virus Type 2 Infection Increases the Risk of Subsequent Episodes of Bacterial Vaginosis

    PubMed Central

    Masese, Linnet; Baeten, Jared M.; Richardson, Barbra A.; Bukusi, Elizabeth; John-Stewart, Grace; Jaoko, Walter; Shafi, Juma; Kiarie, James; McClelland, R. Scott

    2014-01-01

    Herpes simplex virus type 2 (HSV-2) infected women have a higher prevalence of bacterial vaginosis (BV) compared to HSV-2-seronegative women. To explore the temporal association between these conditions, we evaluated the frequency of BV episodes before and after HSV-2 acquisition in a prospective study of 406 HSV-2/HIV-1-seronegative Kenyan women, of whom 164 acquired HSV-2. Incident HSV-2 was associated with increased likelihood of BV (adjusted OR, 1.28; 95% CI, 1.05–1.56; P = .01). Our findings strengthen the evidence for a causal link between genital HSV-2 infection and disruption of the vaginal microbiota. PMID:24273042

  2. Prospects and Perspectives for Development of a Vaccine Against Herpes Simplex Virus Infections

    PubMed Central

    McAllister, Shane C.; Schleiss, Mark R.

    2014-01-01

    Herpes simplex viruses 1 and -2 are human pathogens that lead to significant morbidity and mortality in certain clinical settings. The development of effective antiviral medications, however, has had little discernible impact on the epidemiology of these pathogens, largely because the majority of infections are clinically silent. Decades of work have gone into various candidate HSV vaccines, but to date none has demonstrated sufficient efficacy to warrant licensure. This review examines developments in HSV immunology and vaccine development published since 2010, and assesses the prospects for improved immunization strategies that may result in an effective, licensed vaccine in the near future. PMID:25077372

  3. A mouse model for testing the pathogenicity of equine herpes virus-1 strains.

    PubMed

    van Woensel, P A; Goovaerts, D; Markx, D; Visser, N

    1995-07-01

    A mouse model was developed for testing the pathogenicity of equine herpes virus-1 (EHV-1) strains. The model was validated with EHV-1 strains that are known to be of a low or high pathogenicity in horses. From all parameters tested, the safety index, which was calculated from the body weights of the mice after infection, proved to be the best predictive parameter. When this parameter was used, good and reliable correlations were found with the pathogenicity of the EHV-1 strains in horses. This method enabled the differentiation between the two experimental EHV-1 strains whose genetic backgrounds were supposedly equal.

  4. Application of polymerase chain reaction (PCR) for diagnosis of equine herpes virus-1 (EHV-1).

    PubMed

    Gupta, A K; Singh, B K; Yadav, M P

    1996-11-01

    Fifty aborted foetus samples were diagnosed for the presence of equine herpes virus-1 (EHV-1) by polymerase chain reaction (PCR) technique. Specific primer pair for amplification of a particular segment of EHV-1 DNA in gc region having 3 Hae III restriction endonuclease sites was used. A 409 base pair segment obtained as PCR amplification product in 9 samples was digested with Hae III to confirm the presence of EHV-1 as the infectious agent in aborted tissues. It was observed that PCR technique was more sensitive, specific and rapid than the conventional virological diagnostic methods.

  5. [Mechanisms of Chlamydia trachomatis and herpes simplex virus persistence during viral-bacterial infection].

    PubMed

    Bekhalo, V A; Sysoliatina, E V; Nagurskaia, E V

    2009-01-01

    Possible mechanisms of persistence on the example of Chlamydia trachomatis in conditions of herpes simplex virus type 2 (HSV-2) superinfection in vitro and in vivo are described. Emergence of persisting forms of Chlamydia as well as factors influencing on this process are considered. Contemporary views on pathogenesis of viral-bacterial infection with HSV-2 and C. trachomatis as well as interactions of the agents with local immunity factors are described. It was suggested that there are signaling pathways through which HSV-2 changes life cycle of Chlamydia.

  6. Prospects and perspectives for development of a vaccine against herpes simplex virus infections.

    PubMed

    McAllister, Shane C; Schleiss, Mark R

    2014-11-01

    Herpes simplex viruses 1 and 2 are human pathogens that lead to significant morbidity and mortality in certain clinical settings. The development of effective antiviral medications, however, has had little discernible impact on the epidemiology of these pathogens, largely because the majority of infections are clinically silent. Decades of work have gone into various candidate HSV vaccines, but to date none has demonstrated sufficient efficacy to warrant licensure. This review examines developments in HSV immunology and vaccine development published since 2010, and assesses the prospects for improved immunization strategies that may result in an effective, licensed vaccine in the near future.

  7. Herpes simplex virus type 1 encephalitis and unusual retinitis in a patient with systemic lupus erythematosus.

    PubMed

    Zhang, L; Liu, J J; Li, M T

    2013-11-01

    In this report we discuss a case of a patient with systemic lupus erythematosus who developed herpes simplex virus type 1(HSV-1) infection presenting with encephalitis as well as necrotic and non-necrotic retinitis. The patient presented with typical clinical symptoms and radiologic abnormalities consistent with HSV-1 encephalitis and HSV-1 retinitis in patients with HIV infection, but lacked cerebrospinal fluid pleocytosis and had bilateral retinitis with poor visual acuity. To the best of our knowledge, this is the first such case reported in the literature.

  8. Treatment of herpes simplex virus infections in pediatric patients: current status and future needs.

    PubMed

    James, S H; Whitley, R J

    2010-11-01

    Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are members of the Herpesviridae family and are characterized by their ability to establish latency after primary infection and subsequently reactivate. HSV infections in the neonatal and pediatric populations range from uncomplicated mucocutaneous diseases to severe, life-threatening infections involving the central nervous system (CNS). The antiviral agent acyclovir has significantly improved treatment outcomes of HSV infections, including the frequency of mucocutaneous recurrences and mortality associated with CNS and disseminated infections.

  9. Pathogenesis of herpes simplex virus types 1 and 2 in mice after various routes of inoculation.

    PubMed Central

    Renis, H E; Eidson, E E; Mathews, J; Gray, J E

    1976-01-01

    The pathogenesis of herpes simplex virus (HSV) types 1 and 2 was compared after inoculation of mice by different routes. Intravaginal inoculation of HSV-1 and HSV-2 produced a local infection, with virus recovery from the vagina through 5 days. Virus was recovered from the spinal cords 4 to 5 days after inoculation but not from liver, kidney, lung, spleen, or blood. Intravenous or intraperitoneal inoculation of HSV-2 produced a focal necrotic hepatitis similar to that described previously (S. C. Mogenson, B. Teisner, and H.K. Andersen, 1974). The viral etiology of the liver lesions was confirmed by virus isolation (through 4 days) and electron microscopy. No evidence of infection of the kidney, lung, blood, or spleen was observed, although virus was isolated from spinal cord homogenates 7 days after inoculation. HSV-1 inoculation by the intraperitoneal or intravenous route resulted in virus isolation from the kidney during the 7-day harvest period, without producing overt pathological changes. Virus was isolated from spinal cord homogenates 2 to 3 days after HSV-1 inoculation but not from homogenates prepared from spleen, lung, or blood. Increases in serum transaminase activity were observed after systemic (intravenous) inoculation of HSV-2 but not after HSV-1 inoculation. Images PMID:184048

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

    PubMed

    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.

  11. ONCOLYTIC HERPES SIMPLEX VIRUS 1 (HSV-1) VECTORS: INCREASING TREATMENT EFFICACY AND RANGE THROUGH STRATEGIC VIRUS DESIGN

    PubMed Central

    Carson, J.; Haddad, D.; Bressman, M.; Fong, Y.

    2012-01-01

    SUMMARY Viruses have long been considered potential anticancer treatments. Wild-type viruses have been tested as anticancer agents in clinical trials since the 1960s. The possibility of viral oncolysis as an alternate cancer therapy was transformed by the emergence of modern genetic engineering. The herpes simplex virus (HSV) family offers particular advantages for use as a viral oncolytic. The engineered vectors that make up oncolytic HSVs (oHSVs) have demonstrated remarkable safety in clinical trials, with some evidence of efficacy. The past decade has seen a focus on increasing the efficacy of oncolytic vectors by adding exogenous transgenes to enhance tumor destruction. The current paper describes the various strategies for engineering HSV for increased cancer tissue specificity and efficacy. Presented are the rationale, preclinical data and clinical data where available. This is meant to illustrate a basic framework for the development of a novel therapy meant to exploit the viral life cycle for the killing of cancer. PMID:22287818

  12. Functional hierarchy of herpes simplex virus type-1 membrane proteins in corneal infection and virus transmission to ganglionic neurons.

    PubMed

    Kim, In-Joong; Saied, Ahmad A; Chouljenko, Vladimir N; Subramanian, Ramesh; Kousoulas, Konstantin G

    2014-12-01

    To determine the relative importance of viral glycoproteins gK, gM, gE and the membrane protein UL11 in infection of mouse corneas and ganglionic neurons. Mouse eyes were scarified and infected with herpes simplex virus (HSV)-1(F), gE-null, gM-null, gK-null, or UL11-null viruses. Clinical signs of ocular disease were monitored daily. Virus shedding was determined at 24, 48 and 72 h post infection. Viral DNA within trigeminal ganglia (TG) was quantified by quantitative PCR at 30 d post infection. The gE-null virus replicated as efficiently as the parental virus and formed viral plaques approximately half-the-size in comparison with the HSV-1(F) wild-type virus. The UL11-null and gM-null viruses replicated approximately one log less efficiently than the wild-type virus, and formed plaques that were on average one-third the size and one-half the size of the wild-type virus, respectively. The gK-null virus replicated more than 3-logs less efficiently than the wild-type virus and formed very small plaques (5-10 cells). Mice infected with the wild-type virus exhibited mild clinical ocular symptoms, while mice infected with the mutant viruses did not show any significant ocular changes. The wild-type virus produced the highest virus shedding post infection followed by the gM-null, gE-null and UL11-null viruses, while no gK-null virus was detected at any time point. All TG collected from mice infected with the wild-type virus and 6-of-10 of TG retrieved from mice infected with the UL11-null virus contained high numbers of viral genomes. The gE-null and gM-null-infected ganglia contained moderate-to-low number of viral genomes in 4-of-10 and 2-of-10 mice, respectively. No viral genomes were detected in ganglionic tissues obtained from gK-null eye infections. The results show that gK plays the most important role among gM, gE and UL11 in corneal and ganglionic infection in the mouse eye model.

  13. Investigations of Allerton-type herpes virus infection in East African game animals and cattle.

    PubMed

    Plowright, W; Jessett, D M

    1971-06-01

    Neutralization tests with a strain (BA) of Allerton-type herpes virus, derived from a buffalo (Syncerus caffer) were carried out on 924 sera from 17 species of E. African game animals and on cattle sera from Tanzania (2001), Kenya (792) and Uganda (410).Buffalo populations throughout E. Africa showed a very high rate of infection, with all animals over 2 years of age serologically positive. Antibody was present in some giraffe, waterbuck and hippopotamus sera and, less frequently, in impala, eland, bushbuck and oryx. Data are provided on the titres of positive samples; the mean titre of buffalo sera increased with age.Cattle in many localities of N. Tanzania and S. Kenya showed a very high rate of infection, 85-95% of sera from animals more than 2-years old containing antibody; the titres recorded were lower than those in buffaloes. Very high infection rates were also found in Karamoja and Teso (Uganda) and also in some other areas of Kenya, whilst a considerably lower incidence of infection was detected in W. Nile Province of Uganda and in central Tanzania. Differences in infection rates may have been related to herd size and husbandry practices.It was shown that a wave of infection was probably spreading through cattle in N. Tanzania at about the same time as an outbreak of disease occurred in buffaloes and it is suggested that virus transmission may have been by biting flies.No clinical signs attributable to the virus were reported in cattle but mouth lesions similar to those recorded in buffaloes, or nasal lesions, could have passed undetected. Allerton-type virus probably produces a range of clinical syndromes in cattle, closely resembling those associated with some herpes viruses in primates but infection is seldom related in the field to either pseudo-lumpy skin disease, mammillitis or stomatitis.

  14. Occasional presence of herpes viruses in synovial fluid and blood from patients with rheumatoid arthritis and axial spondyloarthritis.

    PubMed

    Burgos, Rubén; Ordoñez, Graciela; Vázquez-Mellado, Janitzia; Pineda, Benjamín; Sotelo, Julio

    2015-10-01

    Viral agents have been suspected as participants of immune-mediated disorders. In the case of rheumatic diseases, the synovial joint cavity represents a secluded area of inflammation which could harbor etiological agents. We analyzed by polymerase chain reaction the possible presence of DNA from various herpes viruses in blood and synovial fluid from patients with either rheumatoid arthritis (n = 18), axial spondyloarthritis (n = 11), or osteoarthritis (n = 8). Relevant findings were as follows: DNA from varicella zoster virus was found in synovial fluid but not in blood mononuclear cells from 33 % of patients with rheumatoid arthritis and in 45 % of patients with axial spondyloarthritis but not in patients with osteoarthritis. Also, DNA from herpes simplex viruses 1 and 2 was found both in the blood and in the synovial fluid from 33 % of patients with rheumatoid arthritis. Our results indicate the occasional presence of DNA from herpes viruses in patients with rheumatoid arthritis or with axial spondyloarthritis. However, these findings might represent a parallel epiphenomenon of viral activation associated either with immunosuppressive therapy or with primary immune disturbances, rather than the etiological participation of herpes viruses in these disorders.

  15. HERP Binds TBK1 To Activate Innate Immunity and Repress Virus Replication in Response to Endoplasmic Reticulum Stress.

    PubMed

    Ge, Maolin; Luo, Zhen; Qiao, Zhi; Zhou, Yao; Cheng, Xin; Geng, Qibin; Cai, Yanyan; Wan, Pin; Xiong, Ying; Liu, Fang; Wu, Kailang; Liu, Yingle; Wu, Jianguo

    2017-09-27

    Host innate immunity is crucial for cellular responses against viral infection sensed by distinct pattern recognition receptors and endoplasmic reticulum (ER) stress. Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and neurological diseases. However, the exact mechanism underlying the link between ER stress induced by EV71 infection and host innate immunity is largely unknown. In this study, we demonstrated that EV71 infection induces the homocysteine-induced ER protein (HERP), a modulator of the ER stress response which is dependent on the participation of MAVS. Virus-induced HERP subsequently stimulates host innate immunity to repress viral replication by promoting type-I IFNs (IFN-α and IFN-β) and type-III IFN (IFN-λ1) expression. Through interacting with TANK-binding kinase 1, HERP amplifies the MAVS signaling and facilitates the phosphorylation and nuclear translocation of IFN regulatory factor 3 and NF-κB to enhance the expression of IFNs, which leads to a broad inhibition of the replication of RNA viruses, including EV71, Sendai virus, influenza A virus, and vesicular stomatitis virus. Therefore, we demonstrated that HERP plays an important role in the regulation of host innate immunity in response to ER stress during the infection of RNA viruses. These findings provide new insights into the mechanism underlying the replication of RNA viruses and the production of IFNs, and also demonstrate a new role of HERP in the regulation of host innate immunity in response to viral infection. Copyright © 2017 by The American Association of Immunologists, Inc.

  16. Herpes biopsy (image)

    MedlinePlus

    ... if a person has been infected with the herpes simplex virus (I or II). This test does not detect the virus itself. If antibodies to the virus are present, the person has been infected with herpes simplex at some point in his or her life. ...

  17. Large Amounts of Reactivated Virus in Tears Precedes Recurrent Herpes Stromal Keratitis in Stressed Rabbits Latently Infected with Herpes Simplex Virus.

    PubMed

    Perng, Guey-Chuen; Osorio, Nelson; Jiang, Xianzhi; Geertsema, Roger; Hsiang, Chinhui; Brown, Don; BenMohamed, Lbachir; Wechsler, Steven L

    2016-01-01

    Recurrent herpetic stromal keratitis (rHSK), due to an immune response to reactivation of herpes simplex virus (HSV-1), can cause corneal blindness. The development of therapeutic interventions such as drugs and vaccines to decrease rHSK have been hampered by the lack of a small and reliable animal model in which rHSK occurs at a high frequency during HSV-1 latency. The aim of this study is to develop a rabbit model of rHSK in which stress from elevated temperatures increases the frequency of HSV-1 reactivations and rHSK. Rabbits latently infected with HSV-1 were subjected to elevated temperatures and the frequency of viral reactivations and rHSK were determined. In an experiment in which rabbits latently infected with HSV-1 were subjected to ill-defined stress as a result of failure of the vivarium air conditioning system, reactivation of HSV-1 occurred at over twice the normal frequency. In addition, 60% of eyes developed severe rHSK compared to <1% of eyes normally. All episodes of rHSK were preceded four to five days prior by an unusually large amount of reactivated virus in the tears of that eye and whenever this unusually large amount of reactivated virus was detected in tears, rHSK always appeared 4-5 days later. In subsequent experiments using well defined heat stress the reactivation frequency was similarly increased, but no eyes developed rHSK. The results reported here support the hypothesis that rHSK is associated not simply with elevated reactivation frequency, but rather with rare episodes of very high levels of reactivated virus in tears 4-5 days earlier.

  18. Large Amounts of Reactivated Virus in Tears Precedes Recurrent Herpes Stromal Keratitis in Stressed Rabbits Latently Infected with Herpes Simplex Virus

    PubMed Central

    Perng, Guey-Chuen; Osorio, Nelson; Jiang, Xianzhi; Geertsema, Roger; Hsiang, Chinhui; Brown, Don; BenMohamed, Lbachir; Wechsler, Steven L.

    2017-01-01

    Aim Recurrent herpetic stromal keratitis (rHSK), due to an immune response to reactivation of herpes simplex virus (HSV-1), can cause corneal blindness. The development of therapeutic interventions such as drugs and vaccines to decrease rHSK have been hampered by the lack of a small and reliable animal model in which rHSK occurs at a high frequency during HSV-1 latency. The aim of this study is to develop a rabbit model of rHSK in which stress from elevated temperatures increases the frequency of HSV-1 reactivations and rHSK. Materials and methods Rabbits latently infected with HSV-1 were subjected to elevated temperatures and the frequency of viral reactivations and rHSK were determined. Results In an experiment in which rabbits latently infected with HSV-1 were subjected to ill-defined stress as a result of failure of the vivarium air conditioning system, reactivation of HSV-1 occurred at over twice the normal frequency. In addition, 60% of eyes developed severe rHSK compared to <1% of eyes normally. All episodes of rHSK were preceded four to five days prior by an unusually large amount of reactivated virus in the tears of that eye and whenever this unusually large amount of reactivated virus was detected in tears, rHSK always appeared 4–5 days later. In subsequent experiments using well defined heat stress the reactivation frequency was similarly increased, but no eyes developed rHSK. Conclusions The results reported here support the hypothesis that rHSK is associated not simply with elevated reactivation frequency, but rather with rare episodes of very high levels of reactivated virus in tears 4–5 days earlier. PMID:25859798

  19. Turning killer into cure -- the story of oncolytic herpes simplex viruses.

    PubMed

    Zhang, Shaun Xiaoliu

    2015-11-01

    Viruses have the intrinsic capability to kill host cells. Even when the initial infection consists of only a few viruses, they can reproduce themselves in large quantities within a short time and quickly spread to nearby cells, causing substantial tissue damage. These same infectious properties become desirable if they can be converted into killer agents with specificity for malignant cells. Cancer virotherapy is doing exactly that by modifying viruses in ways that allow them to replicate in malignant cells but not in normal cells. Although relatively young, the field has seen significant progress in recent years. For example, the most recent phase III trial data on a herpes simplex virus (HSV)-based oncolytic virus (T-VEC) show substantial improvement in objective and durable responses over the control arm in melanoma patients, prompting speculation that a virotherapy may receive FDA approval for clinical use in the very near future. This review focuses on HSV-based oncolytic viruses, from their early history to their most recent development, with discussion of promising directions for further improvement.

  20. Antiviral effects of 28-deacetylsendanin on herpes simplex virus-1 replication.

    PubMed

    Kim, M; Kim, S K; Park, B N; Lee, K H; Min, G H; Seoh, J Y; Park, C G; Hwang, E S; Cha, C Y; Kook, Y H

    1999-09-01

    The compound purified from the fruit of Melia azedarach exerted an antiviral effect on herpes simplex virus-1 (HSV-1) in Vero cells. It was identified as 28-deacetylsendanin (28-DAS). The 50% inhibitory concentration (IC50) of 28-DAS was 1.46 microg/ml without cytotoxicity at 400 microg/ml on Vero cells. Electron microscopy showed that low electron-dense cores of newly synthesized nucleocapsids remained in swollen nuclei and no extracellular virus particles were observed at 15 h p.i. Consistent with this result, it was confirmed by a plaque assay that few infectious progeny viruses were released from the 28-DAS-treated virus-infected cells at 24 h p.i. Intracellular viruses in 28-DAS-treated virus-infected cells were 23% of untreated and infected cells. The synthesis of thymidine kinase (TK) was reduced by 28-DAS at early stage. In conclusion, 28-DAS inhibited the replication of HSV-1, reduced the synthesis of HSV-1 TK, and led to the formation of defective nucleocapsids.

  1. The potential application of a transcriptionally regulated oncolytic herpes simplex virus for human cancer therapy

    PubMed Central

    Miao, L; Fraefel, C; Sia, K C; Newman, J P; Mohamed-Bashir, S A; Ng, W H; Lam, P Y P

    2014-01-01

    Background: Emerging studies have shown the potential benefit of arming oncolytic viruses with therapeutic genes. However, most of these therapeutic genes are placed under the regulation of ubiquitous viral promoters. Our goal is to generate a safer yet potent oncolytic herpes simplex virus type-1 (HSV-1) for cancer therapy. Methods: Using bacterial artificial chromosome (BAC) recombineering, a cell cycle-regulatable luciferase transgene cassette was replaced with the infected cell protein 6 (ICP6) coding region (encoded for UL39 or large subunit of ribonucleotide reductase) of the HSV-1 genome. These recombinant viruses, YE-PC8, were further tested for its proliferation-dependent luciferase gene expression. Results: The ability of YE-PC8 to confer proliferation-dependent transgene expression was demonstrated by injecting similar amount of viruses into the tumour-bearing region of the brain and the contralateral normal brain parenchyma of the same mouse. The results showed enhanced levels of luciferase activities in the tumour region but not in the normal brain parenchyma. Similar findings were observed in YE-PC8-infected short-term human brain patient-derived glioma cells compared with normal human astrocytes. intratumoural injection of YE-PC8 viruses resulted in 77% and 80% of tumour regression in human glioma and human hepatocellular carcinoma xenografts, respectively. Conclusion: YE-PC8 viruses confer tumour selectivity in proliferating cells and may be developed further as a feasible approach to treat human cancers. PMID:24196790

  2. Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism.

    PubMed

    Vastag, Livia; Koyuncu, Emre; Grady, Sarah L; Shenk, Thomas E; Rabinowitz, Joshua D

    2011-07-01

    Viruses rely on the metabolic network of the host cell to provide energy and macromolecular precursors to fuel viral replication. Here we used mass spectrometry to examine the impact of two related herpesviruses, human cytomegalovirus (HCMV) and herpes simplex virus type-1 (HSV-1), on the metabolism of fibroblast and epithelial host cells. Each virus triggered strong metabolic changes that were conserved across different host cell types. The metabolic effects of the two viruses were, however, largely distinct. HCMV but not HSV-1 increased glycolytic flux. HCMV profoundly increased TCA compound levels and flow of two carbon units required for TCA cycle turning and fatty acid synthesis. HSV-1 increased anapleurotic influx to the TCA cycle through pyruvate carboxylase, feeding pyrimidine biosynthesis. Thus, these two related herpesviruses drive diverse host cells to execute distinct, virus-specific metabolic programs. Current drugs target nucleotide metabolism for treatment of both viruses. Although our results confirm that this is a robust target for HSV-1, therapeutic interventions at other points in metabolism might prove more effective for treatment of HCMV.

  3. Enhanced replication of herpes simplex virus type 1 in human cells

    SciTech Connect

    Miller, C.S.; Smith, K.O. )

    1991-02-01

    The effects of DNA-damaging agents on the replication of herpes simplex virus type 1 (HSV-1) were assessed in vitro. Monolayers of human lung fibroblast cell lines were exposed to DNA-damaging agents (methyl methanesulfonate (MMS), methyl methanethiosulfonate (MMTS), ultraviolet light (UV), or gamma radiation (GR)) at specific intervals, before or after inoculation with low levels of HSV-1. The ability of cell monolayers to support HSV-1 replication was measured by direct plaque assay and was compared with that of untreated control samples. In this system, monolayers of different cell lines infected with identical HSV-1 strains demonstrated dissimilar levels of recovery of the infectious virus. Exposure of DNA-repair-competent cell cultures to DNA-damaging agents produced time-dependent enhanced virus replication. Treatment with agent before virus inoculation significantly (p less than 0.025) increased the number of plaques by 10 to 68%, compared with untreated control cultures, while treatment with agent after virus adsorption significantly increased (p less than 0.025) the number of plaques by 7 to 15%. In a parallel series of experiments, cells deficient in DNA repair (xeroderma pigmentosum) failed to support enhanced virus replication. These results suggest that after exposure to DNA-damaging agents, fibroblasts competent in DNA repair amplify the replication of HSV-1, and that DNA-repair mechanisms that act on a variety of chromosomal lesions may be involved in the repair and biological activation of HSV-1 genomes.

  4. The Significance of Herpes Simplex for School Nurses

    ERIC Educational Resources Information Center

    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…

  5. The Significance of Herpes Simplex for School Nurses

    ERIC Educational Resources Information Center

    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…

  6. Correlation between detection of herpes simplex virus in oral secretions by PCR and susceptibility to experimental UV radiation-induced herpes labialis.

    PubMed Central

    Kriesel, J D; Pisani, P L; McKeough, M B; Baringer, J R; Spruance, S L

    1994-01-01

    We examined the oral secretions of 25 patients for herpes simplex virus (HSV) at the time of and following experimental UV radiation (UVR). HSV was detected in one or more oral secretion specimens in 5 of 12 (42%) cases by cell culture and in 8 of 12 (67%) cases by PCR. On the day of UVR, HSV was detected in 1 of 12 (8%) patients who developed a lip lesion and 2 of 16 (13%) patients who did not (the difference is not significant). We conclude that PCR is more sensitive than culture in the detection of HSV and that HSV is not shed with increased frequency from the oral cavity before the development of UVR-induced herpes labialis. PMID:7883911

  7. Human papilloma virus, herpes simplex virus and epstein barr virus in oral squamous cell carcinoma from eight different countries.

    PubMed

    Jalouli, Jamshid; Jalouli, Miranda M; Sapkota, Dipak; Ibrahim, Salah O; Larsson, Per-Anders; Sand, Lars

    2012-02-01

    Oral squamous cell carcinoma (OSCC) is a major health problem in many parts of the world, and the major causative agents are thought to be the use of alcohol and tobacco. Oncogenic viruses have also been suggested to be involved in OSCC development. This study investigated the prevalence of human papillomaviruses (HPV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) in 155 OSCC from eight different countries from different ethnic groups, continents and with different socioeconomic backgrounds. 41 A total of OSCCs were diagnosed in the tongue (26%) and 23 in the floor of the mouth (15%); the other 91 OSCCs were diagnosed in other locations (59%). The patients were also investigated regarding the use of alcohol and smoking and smokeless tobacco habits. Tissue samples were obtained from formalin-fixed, paraffin-embedded samples of the OSCC. DNA was extracted and the viral genome was examined by single, nested and semi-nested PCR assays. Sequencing of double-stranded DNA from the PCR product was carried out. Following sequencing of the HPV-, HSV- and EBV-positive PCR products, 100% homology between the sampels was found. Of all the 155 OSCCs examined, 85 (55%) were positive for EBV, 54 (35%) for HPV and 24 (15%) for HSV. The highest prevalence of HPV was seen in Sudan (65%), while HSV (55%) and EBV (80%) were most prevalent in the UK. In 34% (52/155) of all the samples examined, co-infection by two (46/155=30%) or three (6/155=4%) virus specimens was detected. The most frequent double infection was HPV with EBV in 21% (32/155) of all OSCCs. There was a statistically significant higher proportion of samples with HSV (p=0.026) and EBV (p=0.015) in industrialized countries (Sweden, Norway, UK and USA) as compared to developing countries (Sudan, India, Sri Lanka and Yemen). Furthermore, there was a statistically significant higher co-infection of HSV and EBV in samples from industrialized countries (p=0.00031). No firm conclusions could be drawn regarding the

  8. Intracerebral propagation of Alzheimer's disease: strengthening evidence of a herpes simplex virus etiology

    PubMed Central

    Ball, Melvyn J.; Lukiw, Walter J.; Kammerman, Eli M.; Hill, James M.

    2012-01-01

    Background A faulty human protein, abnormally phosphorylated tau, was recently publicized to spread “like a virus” from neuron to neuron in Alzheimer patients' brains. For several decades, we have been amassing arguments showing that herpes simplex virus type 1 (HSV-1), not p-tau, propagates this inter-neuronal, trans-synaptic pathological cascade. Methods We reiterate convincing data from our own (and other) laboratories, reviewing the first anatomic foothold neurofibrillary tangles gain in brainstem and/or entorhinal cortex; the chronic immunosurveillance cellularity of the trigeminal ganglia wherein HSV-1 awakens from latency to reactivate; the inabilities of p-tau protein's physical properties to promote it to jump synapses; the amino-acid homology between human p-tau and VP22, a key target for phosphorylation by HSV serine/threonine-protein kinase UL13; and the exosomic secretion of HSV-1-infected cells' L-particles, attesting to the cell-to-cell passage of microRNAs of herpes viruses. Results The now-maturing construct that reactivated HSV-1 best accounts for the intracerebral propagation of AD changes in the human brain should at last seem highly attractive. This hypothesis might even explain statins' apparent mechanism in some studies for lowering AD incidence. Conclusion Provided that funding agencies will quickly ignite a new realm of investigation, the rejuvenated enthusiasm for testing this optimistic construct holds incalculable potential for rapid, efficacious clinical application, through already available and relatively safe anti-viral therapeutics. PMID:23159044

  9. Herpes Simplex Virus Hepatitis in an Immunocompetent Host Resembling Hepatic Pyogenic Abscesses

    PubMed Central

    Mehta, Amit; Salama, Gayle; Hissong, Erika; Rosenblatt, Russell; Cantor, Michael; Helfgott, David; Marks, Kristen

    2016-01-01

    Herpes simplex virus (HSV) hepatitis represents a rare complication of HSV infection, which can progress to acute liver failure and, in some cases, death. We describe an immunocompetent 67-year-old male who presented with one week of fever and abdominal pain. Computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen showed multiple bilobar hepatic lesions, some with rim enhancement, compatible with liver abscesses. Subsequent liver biopsy, however, revealed hepatocellular necrosis, HSV-type intranuclear inclusions, and immunostaining positive for herpes virus type 2 (HSV-2). Though initially treated with broad-spectrum antibiotics, following histologic diagnosis of HSV hepatitis, the patient was transitioned to intravenous acyclovir for four weeks and he achieved full clinical recovery. Given its high mortality and nonspecific presentation, one should consider HSV hepatitis in all patients with acute hepatitis with multifocal hepatic lesions of unknown etiology. Of special note, this is only the second reported case of HSV liver lesions mimicking pyogenic abscesses on CT and MRI. PMID:27872770

  10. Primary herpes virus infection and ischemic stroke in childhood: a new association?

    PubMed

    Terlizzi, Vito; Improta, Federica; Di Fraia, Teresa; Sanguigno, Eduardo; D'Amico, Alessandra; Buono, Salvatore; Raia, Valeria; Boccia, Gabriella

    2014-09-01

    We describe, to our knowledge, the first case of arterial ischemic stroke after primary herpes simplex virus type 1 (HSV1) infection in a previously healthy child, without signs of encephalitis. A 10-year-old previously healthy girl was admitted to our hospital with acute left-sided hemiparesis which involved the lower half of her face. Submandibular lymphadenitis and oral vesicular lesions were present. MRI confirmed the suspicion of an acute ischemic stroke. Immunoglobulin M antibodies to HSV1 were detected. Cerebrospinal fluid polymerase chain reaction for herpes virus was negative. She was treated with aspirin (3mg/kg) and intravenous acyclovir (10mg/kg every 8 hours) for 21 days. Immunoglobulin G antibodies to HSV1 appeared 16 days after admission. Twelve months after her hospitalization the patient's examination was normal. Stroke should be considered a possible complication of HSV1 primary infection. Guidelines for the management of acute stroke in children are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  12. Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management.

    PubMed

    Bradshaw, Michael J; Venkatesan, Arun

    2016-07-01

    Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be life-saving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

  13. Activation of DNA Damage Response Induced by the Kaposi’s Sarcoma-Associated Herpes Virus

    PubMed Central

    Di Domenico, Enea Gino; Toma, Luigi; Bordignon, Valentina; Trento, Elisabetta; D’Agosto, Giovanna; Cordiali-Fei, Paola; Ensoli, Fabrizio

    2016-01-01

    The human herpes virus 8 (HHV-8), also known as Kaposi sarcoma-associated herpes virus (KSHV), can infect endothelial cells often leading to cell transformation and to the development of tumors, namely Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and the plasmablastic variant of multicentric Castleman’s disease. KSHV is prevalent in areas such as sub-Saharan Africa and the Mediterranean region presenting distinct genotypes, which appear to be associated with differences in disease manifestation, according to geographical areas. In infected cells, KSHV persists in a latent episomal form. However, in a limited number of cells, it undergoes spontaneous lytic reactivation to ensure the production of new virions. During both the latent and the lytic cycle, KSHV is programmed to express genes which selectively modulate the DNA damage response (DDR) through the activation of the ataxia telangiectasia mutated (ATM) pathway and by phosphorylating factors associated with the DDR, including the major tumor suppressor protein p53 tumor suppressor p53. This review will focus on the interplay between the KSHV and the DDR response pathway throughout the viral lifecycle, exploring the putative molecular mechanism/s that may contribute to malignant transformation of host cells. PMID:27258263

  14. Role of Bacterial Exopolysaccharides as Agents in Counteracting Immune Disorders Induced by Herpes Virus

    PubMed Central

    Gugliandolo, Concetta; Spanò, Antonio; Maugeri, Teresa L.; Poli, Annarita; Arena, Adriana; Nicolaus, Barbara

    2015-01-01

    Extreme marine environments, such as the submarine shallow vents of the Eolian Islands (Italy), offer an almost unexplored source of microorganisms producing unexploited and promising biomolecules for pharmaceutical applications. Thermophilic and thermotolerant bacilli isolated from Eolian vents are able to produce exopolysaccharides (EPSs) with antiviral and immunomodulatory effects against Herpes simplex virus type 2 (HSV-2). HSV-2 is responsible for the most common and continuously increasing viral infections in humans. Due to the appearance of resistance to the available treatments, new biomolecules exhibiting different mechanisms of action could provide novel agents for treating viral infections. The EPSs hinder the HSV-2 replication in human peripheral blood mononuclear cells (PBMC) but not in WISH (Wistar Institute Susan Hayflic) cells line, indicating that cell-mediated immunity was involved in the antiviral activity. High levels of Th1-type cytokines were detected in PBMC treated with all EPSs, while Th2-type cytokines were not induced. These EPSs are water soluble exopolymers able to stimulate the immune response and thus contribute to the antiviral immune defense, acting as immunomodulators. As stimulants of Th1 cell-mediated immunity, they could lead to the development of novel drugs as alternative in the treatment of herpes virus infections, as well as in immunocompromised host. PMID:27682100

  15. Defensive effects of a fucoidan from brown alga Undaria pinnatifida against herpes simplex virus infection.

    PubMed

    Hayashi, Kyoko; Nakano, Takahisa; Hashimoto, Minoru; Kanekiyo, Kenji; Hayashi, Toshimitsu

    2008-01-01

    Fucoidan, a sulfated polysaccharide isolated from an edible brown alga Undaria pinnatifida, was previously shown to be a potent inhibitor of the in vitro replication of herpes simplex virus type 1 (HSV-1). HSV-1 is a member of herpes viruses that cause infections ranging from trivial mucosal ulcers to life-threatening disorders in immunocompromised hosts. In the in vivo conditions, the replication of HSV-1 is controlled under the immunoresponse coordinated by both the innate and adaptive immune systems. In the present study, the effects of the fucoidan were examined on in vivo viral replication and the host's immune defense system. Oral administration of the fucoidan protected mice from infection with HSV-1 as judged from the survival rate and lesion scores. Phagocytic activity of macrophages and B cell blastogenesis in vitro were significantly stimulated by the fucoidan, while no significant change in the release of NO(2)(-) by macrophages was observed. In in vivo studies, oral administration of the fucoidan produced the augmentation of NK activity in HSV-1-infected mice immunosuppressed by 5-fluorouracil treatment. CTL activity in HSV-1-infected mice was also enhanced by oral administration of the fucoidan. The production of neutralizing antibodies in the mice inoculated with HSV-1 was significantly promoted during the oral administration of the fucoidan for 3 weeks. These results suggested that oral intake of the fucoidan might take the protective effects through direct inhibition of viral replication and stimulation of both innate and adaptive immune defense functions.

  16. Early human herpes virus type 6 reactivation in umbilical cord blood allogeneic stem cell transplantation.

    PubMed

    Cirrone, Frank; Ippoliti, Cindy; Wang, Hanhan; Zhou, Xi Kathy; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; van Besien, Koen

    2016-11-01

    Human herpes virus type 6 can reactivate in patients after allogeneic stem cell transplantation and has been associated with serious sequelae such as delayed engraftment and an increased risk of developing acute graft-versus-host disease (GVHD). This study investigated human herpes virus type 6 (HHV-6) reactivation within 60 days of transplantation in stem cell transplants utilizing single umbilical cord blood, double umbilical cord blood, or umbilical cord blood plus haploidentical stem cells. Of 92 patients, 60 (65%) had HHV-6 reactivation. Reactivation was not significantly influenced by any patient characteristics, disease characteristics, or by stem cell source (umbilical cord blood only versus haploidentical plus umbilical cord blood). We did not observe any impact of HHV-6 reactivation on neutrophil or platelet count recovery or on relapse-free survival. HHV-6 reactivation was associated with subsequent development of prerelapse acute GVHD (HR = 3.00; 95% CI, 1.4 to 6.4; p = 0.004).

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

    PubMed

    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.

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

    PubMed

    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.

  19. Membrane proteins specified by herpes simplex viruses. V. Identification of an Fc-binding glycoprotein.

    PubMed Central

    Baucke, R B; Spear, P G

    1979-01-01

    A glycoprotein with affinity for the Fc region of immunoglobulin was isolated from extracts of cultured cells infected with herpes simplex virus type 1, and experiments were done to characterize its properties and to investigate whether it could account for the Fc-binding activity previously demonstrated on the surfaces of intact herpes simplex virus-infected cells. The technique of affinity chromatography was used to identify and isolate the Fc-binding glycoprotein and to demonstrate the specificity of its interaction with immunoglobulin G-Fc. Although three electrophoretically distinguishable Fc-binding polypeptides were identified by affinity chromatography, these three species appear to be different forms of the same translation product, based on comparisons of proteolytic digestion products and on the kinetics of appearance of each form after a brief pulse with radioactive amino acids. The results suggest that one polypeptide, designated pE, is processed to yield gE1, which is in turn processed to yield gE2. Both gE1 and gE2 are glycosylated membrane proteins and both can be labeled by the lactoperoxidase-catalyzed radioiodination of intact infected cells, indicating the presence of these proteins in surface membranes of the cells. Increases in the amounts of gE1 and gE2 at the cell surface were found to parallel the increase in Fc-binding activity of intact infected cells. Images PMID:229267

  20. Severe acute disseminated encephalomyelitis with clinical findings of transverse myelitis after herpes simplex virus infection.

    PubMed

    Sarioglu, Berrak; Kose, Seda Sirin; Saritas, Serdar; Kose, Engin; Kanik, Ali; Helvaci, Mehmet

    2014-11-01

    ADEM is a central nervous disease that leads to myelin damage as a result of autoimmune response that develops after infections or vaccination. Herpes Simplex Virus (HSV) infection rarely leads to ADEM. 25-month-old male due to urinary retention, paradoxical respiration and muscle weakness after herpetic gingivostomatitis diagnosed as transverse myelitis. In follow-up with cranial and spinal magnetic resonance imaging multiple lesions were demonstrated. Electroneuromyography findings were compatible with acute sensorimotor neuropathy, serum anti-GM2 antibodies and Herpes Simplex Virus (HSV) Type 1/2 IgM / IgG detected negative and positivite, respectively. With these findings he was diagnosed acute disseminated encephalomyelitis (ADEM) following HSV infection. Although acyclovir, intravenous immunoglobulin, methylprednisolone and plasmapheresis therapies, he is still in intensive physical therapy program with heavy sequel. In our case, ADEM demonstrated transverse myelitis clinic after HSV infection which is rarely seen in literature. As well as clinic and spinal imaging findings, cranial imaging findings helped establishment of ADEM diagnosis. To our best knowledge, HSV is a rare etiological and probably the poor prognostic factor of ADEM. © The Author(s) 2014.

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

    PubMed

    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).

  2. Activation of DNA Damage Response Induced by the Kaposi's Sarcoma-Associated Herpes Virus.

    PubMed

    Di Domenico, Enea Gino; Toma, Luigi; Bordignon, Valentina; Trento, Elisabetta; D'Agosto, Giovanna; Cordiali-Fei, Paola; Ensoli, Fabrizio

    2016-06-01

    The human herpes virus 8 (HHV-8), also known as Kaposi sarcoma-associated herpes virus (KSHV), can infect endothelial cells often leading to cell transformation and to the development of tumors, namely Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and the plasmablastic variant of multicentric Castleman's disease. KSHV is prevalent in areas such as sub-Saharan Africa and the Mediterranean region presenting distinct genotypes, which appear to be associated with differences in disease manifestation, according to geographical areas. In infected cells, KSHV persists in a latent episomal form. However, in a limited number of cells, it undergoes spontaneous lytic reactivation to ensure the production of new virions. During both the latent and the lytic cycle, KSHV is programmed to express genes which selectively modulate the DNA damage response (DDR) through the activation of the ataxia telangiectasia mutated (ATM) pathway and by phosphorylating factors associated with the DDR, including the major tumor suppressor protein p53 tumor suppressor p53. This review will focus on the interplay between the KSHV and the DDR response pathway throughout the viral lifecycle, exploring the putative molecular mechanism/s that may contribute to malignant transformation of host cells.

  3. Human cytomegalovirus renders cells non-permissive for replication of herpes simplex viruses

    SciTech Connect

    Cockley, K.D.

    1988-01-01

    The herpes simplex virus (HSV) genome during production infection in vitro may be subject to negative regulation which results in modification of the cascade of expression of herpes virus macromolecular synthesis leading to establishment of HSV latency. In the present study, human embryonic lung (HEL) cells infected with human cytomegalovirus (HCMV) restricted the replication of HSV type-1 (HSV-1). A delay in HSV replication of 15 hr as well as a consistent, almost 1000-fold inhibition of HSV replication in HCMV-infected cell cultures harvested 24 to 72 hr after superinfection were observed compared with controls infected with HSV alone. HSV type-2 (HSV-2) replication was similarly inhibited in HCMV-infected HEL cells. Prior ultraviolet-irradiation (UV) of HCMV removed the block to HSV replication, demonstrating the requirement for an active HCMV genome. HCMV deoxyribonucleic acid (DNA) negative temperature-sensitive (ts) mutants inhibited HSV replications as efficiently as wild-type (wt) HCMV at the non-permissive temperature. Evidence for penetration and replication of superinfecting HSV into HCMV-infected cells was provided by blot hybridization of HSV DNA synthesized in HSV-superinfected cell cultures and by cesium chloride density gradient analysis of ({sup 3}H)-labeled HSV-1-superinfected cells.

  4. Quantitative autoradiographic mapping of herpes simplex virus encephalitis with a radiolabeled antiviral drug

    SciTech Connect

    Saito, Y.; Price, R.W.; Rottenberg, D.A.; Fox, J.J.; Su, T.L.; Watanabe, K.A.; Philips, F.S.

    1982-09-17

    2'-Fluoro-5-methyl-1-..beta..-D-arabinosyluracil (FMAU) labeled with carbon-14 was used to image herpes simplex virus type 1-infected regions of rat brain by quantitative autoradiography. FMAU is a potent antiviral pyrimidine nucleoside which is selectively phosphorylated by virus-coded thymidine kinase. When the labeled FMAU was administered 6 hours before the rats were killed, the selective uptake and concentration of the drug and its metabolites by infected cells (defined by immunoperoxidase staining of viral antigens) allowed quantitative definition and mapping of HSV-1-infected structures in autoradiograms of brain sections. These results shown that quantitative autoradiography can be used to characterize the local metabolism of antiviral drugs by infected cells in vivo. They also suggest that the selective uptake of drugs that exploit viral thymidine kinase for their antiviral effect can, by appropriate labeling, be used in conjunction with clinical neuroimaging techniques to define infected regions of human brain, thereby providing a new approach to the diagnosis of herpes encephalitis in man.

  5. Oligonucleotides designed to inhibit TLR9 block Herpes simplex virus type 1 infection at multiple steps.

    PubMed

    Sauter, Monica M; Gauger, Joshua J L; Brandt, Curtis R

    2014-09-01

    Herpes simplex virus type 1 (HSV-1) is an important human pathogen which requires activation of nuclear factor-kappa B (NFκB) during its replication cycle. The persistent nature of HSV-1 infection, and the emergence of drug-resistant strains, highlights the importance of research to develop new antiviral agents. Toll-like receptors (TLRs) play a prominent role during the early antiviral response by recognizing viral nucleic acid and gene products, activating NFκB, and stimulating the production of inflammatory cytokines. We demonstrate a significant effect on HSV-1 replication in ARPE-19 and Vero cells when oligonucleotides designed to inhibit TLR9 are added 2h prior to infection. A greater than 90% reduction in the yield of infectious virus was achieved at oligonucleotide concentrations of 10-20 μM. TLR9 inhibitory oligonucleotides prevented expression of essential immediate early herpes gene products as determined by immunofluorescence microscopy and Western blotting. TLR9 oligonucleotides also interfered with viral attachment and entry. A TLR9 inhibitory oligonucleotide containing five adjacent guanosine residues (G-ODN) exhibited virucidal activity and inhibited HSV-1 replication when added post-infection. The antiviral effect of the TLR9 inhibitory oligonucleotides did not depend on the presence of TLR9 protein, suggesting a mechanism of inhibition that is not TLR9 specific. TLR9 inhibitory oligonucleotides also reduced NFκB activity in nuclear extracts. Studies using these TLR inhibitors in the context of viral infection should be interpreted with caution.

  6. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus.

    PubMed

    Schlehofer, J R; Ehrbar, M; zur Hausen, H

    1986-07-15

    The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens ("initiators") as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. As reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells.

  7. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus

    SciTech Connect

    Schlehofer, J.R.; Ehrbar, M.; zur Hausen, H.

    1986-07-15

    The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. As reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells.

  8. Performance of the BioPlex 2200 multiplexing immunoassay platform for the detection of herpes simplex virus type 2 specific antibodies in African settings.

    PubMed

    LeGoff, Jérôme; Grésenguet, Gérard; Gody, Chrysostome; Longo, Jean De Dieu; Khonde, Nzambi; Weiss, Helen A; Mayaud, Philippe; Bélec, Laurent

    2011-07-01

    The BioPlex platform was evaluated for the detection of herpes simplex virus 2 (HSV-2) antibodies in sub-Saharan Africa individuals in comparison to clinicovirological standards and compared to HerpeSelect. The sensitivities and specificities were, respectively, 88.9% and 93.5% for BioPlex and 89.9% and 92.7% for HerpeSelect. The agreement between both assays was 95.7%.

  9. Performance of the BioPlex 2200 Multiplexing Immunoassay Platform for the Detection of Herpes Simplex Virus Type 2 Specific Antibodies in African Settings ▿

    PubMed Central

    LeGoff, Jérôme; Grésenguet, Gérard; Gody, Chrysostome; Longo, Jean De Dieu; Khonde, Nzambi; Weiss, Helen A.; Mayaud, Philippe; Bélec, Laurent

    2011-01-01

    The BioPlex platform was evaluated for the detection of herpes simplex virus 2 (HSV-2) antibodies in sub-Saharan Africa individuals in comparison to clinicovirological standards and compared to HerpeSelect. The sensitivities and specificities were, respectively, 88.9% and 93.5% for BioPlex and 89.9% and 92.7% for HerpeSelect. The agreement between both assays was 95.7%. PMID:21562116

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

    PubMed

    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.

  11. A procedure to deliver herpes simplex virus to the murine trigeminal ganglion.

    PubMed

    Whitehead, John L; Ohara, Peter T; Tauscher, Andrew N; LaVail, Jennifer H

    2003-08-01

    Although initial herpes simplex virus (HSV) infections of the cornea are relatively easily treated, recurrent infections following reactivation of latent virus in the sensory ganglion cells are more difficult to treat. Untreated infections may result in severe consequences, including corneal scarring, glaucoma, and encephalitis. To develop such treatments, an experimental in vivo model was needed in which HSV can be applied directly to trigeminal ganglion cells. We have previously developed such a model to examine the mechanisms of HSV spread from trigeminal neurons to corneal epithelial cells. The current paper describes in detail the technical steps required for implementation of that model. Immunocytochemistry and electron microscopy have been used to validate the efficacy of the described procedures. This technique will be useful for future in vivo studies of neurotrophic viral infections of trigeminal ganglion cells.

  12. Chemical sympathectomy increases susceptibility to ocular herpes simplex virus type 1 infection.

    PubMed

    Templeton, Amanda; Nguyen, Gabrielle; Ash, John D; Straub, Rainer H; Carr, Daniel J J

    2008-06-15

    The cornea is one of the most highly innervated tissues in the mammalian host. We hypothesized changes to cornea innervation through chemical sympathectomy would significantly alter the host response to the neurotropic viral pathogen, herpes simplex virus type 1 (HSV-1) following ocular infection. Mice treated with 6-hydroxydopamine hydrobromide displayed reduced tyrosine hydroxylase-positive fibers residing in the cornea. Sympathectomized mice were also found to show a transient rise in virus recovered in infected tissues and succumbed to infection in greater numbers. Whereas there were no differences in infiltrating leukocyte populations including HSV-1-specific cytotoxic T lymphocytes in the infected tissue, an increase in substance P and a decrease in IFN-gamma levels in the trigeminal ganglion but not brain stem of sympathectomized mice were noted. Sympathectomized mice treated with the neurokinin-1 receptor antagonist L703,606 had delayed mortality implicating the involvement of substance P in HSV-1-mediated death.

  13. Absence of tumour necrosis factor facilitates primary and recurrent herpes simplex virus-1 infections.

    PubMed

    Minagawa, Hiroko; Hashimoto, Koji; Yanagi, Yusuke

    2004-02-01

    Tumour necrosis factor (TNF) is an important cytokine in the innate immune response against various infections, including herpes simplex virus (HSV) infection. It has recently become a molecular target of anti-cytokine treatment in certain inflammatory diseases. TNF depletion resulted in a more rapid emergence of infectious HSV-1 in the explant cultures of latently infected trigeminal ganglia (TG), compared with controls. To further evaluate the importance of TNF in the host's defence responses against HSV-1, TNF-knockout mice were challenged via scarified cornea. These mice were more susceptible to primary acute corneal HSV-1 infection than controls, as manifested by an increased mortality rate and higher infectious virus titres in the eyes and TG, indicating that TNF is critical for defence during acute HSV infection. These results imply that the administration of anti-inflammatory TNF antagonists might facilitate the propagation of infectious HSV, resulting in an exacerbation of primary and recurrent acute lesions.

  14. Chemical Sympathectomy Increases Susceptibility to Ocular Herpes Simplex Virus Type 1 Infection

    PubMed Central

    Templeton, Amanda; Nguyen, Gabrielle; Ash, John D.; Straub, Rainer H.; Carr, Daniel J. J.

    2008-01-01

    The cornea is one of the most highly innervated tissues in the mammalian host. We hypothesized changes to cornea innervation through chemical sympathectomy would significantly alter the host response to the neurotropic viral pathogen, herpes simplex virus type 1 (HSV-1) following ocular infection. Mice treated with 6-hydroxydopamine hydrobromide displayed reduced tyrosine hydroxylase-positive fibers residing in the cornea. Sympathectomized mice were also found to show a transient rise in virus recovered in infected tissues and succumbed to infection in greater numbers. Whereas there were no differences in infiltrating leukocyte populations including HSV-1-specific cytotoxic T lymphocytes in the infected tissue, an increase in substance P and a decrease in IFN-γ levels in the trigeminal ganglion but not brain stem of sympathectomized mice were noted. Sympathectomized mice treated with the neurokinin-1 receptor antagonist L703,606 had delayed mortality implicating the involvement of substance P in HSV-1-mediated death. PMID:18495255

  15. Role for herpes simplex virus 1 ICP27 in the inhibition of type I interferon signaling

    SciTech Connect

    Johnson, Karen E.; Song, Byeongwoon; Knipe, David M.

    2008-05-10

    Host cells respond to viral infection by many mechanisms, including the production of type I interferons which act in a paracrine and autocrine manner to induce the expression of antiviral interferon-stimulated genes (ISGs). Viruses have evolved means to inhibit interferon signaling to avoid induction of the innate immune response. Herpes simplex virus 1 (HSV-1) has several mechanisms to inhibit type I interferon production, the activities of ISGs, and the interferon signaling pathway itself. We report that the inhibition of the Jak/STAT pathway by HSV-1 requires viral gene expression and that viral immediate-early protein ICP27 plays a role in downregulating STAT-1 phosphorylation and in preventing the accumulation of STAT-1 in the nucleus. We also show that expression of ICP27 by transfection causes an inhibition of IFN-induced STAT-1 nuclear accumulation. Therefore, ICP27 is necessary and sufficient for at least some of the effects of HSV infection on STAT-1.

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

    PubMed

    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.

  17. Studies on the survival and inactivation of herpes simplex virus type 1 on coins.

    PubMed

    Bardell, D

    1994-01-01

    Survival of herpes simplex virus type 1 (HSV-1) in saliva at room temperature (21-23 degrees C) on 1, 5, 10, and 25 cent coins was studied. There was little or no loss of infectious HSV-1 before 30 min. Between 30 and 60 min there was a 2- to 3-log drop in titre, and with the exception of the 1 cent coin, some infectious virus was still present after 2 h, the longest period studied. The most conspicuous drop in titre occurred with loss of moisture from the saliva. In addition to the drying process, the metals of the coins also contributed to the decline in titre of HSV-1.

  18. Herpes simplex virus NV1020 as a novel and promising therapy for hepatic malignancy

    PubMed Central

    Kelly, Kaitlyn J; Wong, Joyce; Fong, Yuman

    2012-01-01

    Background Patients with hepatic malignancy have a dismal prognosis with standard therapies. NV1020 is an oncolytic herpes simplex virus that has potential to be a safe and effective therapeutic agent for this disease. Objective We set out to discuss the development of NV1020 as an oncolytic agent and explore the potential role of this particular virus in the setting of human hepatic cancer. Methods The scope of this review includes an overview of preclinical experience with NV1020, as well as an examination of current standard and developing therapies for liver cancer. The primary focus, however, is on the safety and potential clinical efficacy of NV1020 against hepatic malignancy. Results/conclusion We have found that NV1020 is a safe, novel therapeutic agent for treatment of refractory hepatic malignancy. PMID:18549346

  19. Oncolytic Herpes Simplex Virus Vectors Fully Retargeted to Tumor-Associated Antigens.

    PubMed

    Uchida, Hiroaki; Hamada, Hirofumi; Nakano, Kenji; Kwon, Heechung; Tahara, Hideaki; Cohen, Justus B; Glorioso, Joseph C

    2017-02-05

    Oncolytic virotherapy is a novel therapeutic modality for malignant diseases that exploits selective viral replication in cancer cells. Herpes simplex virus (HSV) is a promising agent for oncolytic virotherapy due to its broad cell tropism and the identification of mutations that favor its replication in tumor over normal cells. However, these attenuating mutations also tend to limit the potency of current oncolytic HSV vectors that have entered clinical studies. As an alternative, vector retargeting to novel entry receptors has the potential to achieve tumor specificity at the stage of virus entry, eliminating the need for replication-attenuating mutations. Here we summarize the molecular mechanism of HSV entry and recent advances in the development of fully retargeted HSV vectors for oncolytic virotherapy. Retargeted HSV vectors offer an attractive platform for the creation of a new generation of oncolytic HSV with improved efficacy and specificity.

  20. Towards an Understanding of the Herpes Simplex Virus Type 1 Latency-Reactivation Cycle

    PubMed Central

    Perng, Guey-Chuen; Jones, Clinton

    2010-01-01

    Infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system. Recurrent ocular shedding can lead to corneal scarring and vision loss making HSV-1 a leading cause of corneal blindness due to an infectious agent. The primary site of HSV-1 latency is sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease. During latency, the latency-associated transcript (LAT) is abundantly expressed. LAT expression is important for the latency-reactivation cycle in animal models, in part, because it inhibits apoptosis, viral gene expression, and productive infection. A novel transcript within LAT coding sequences (AL3) and small nonprotein coding RNAs are also expressed in trigeminal ganglia of latently infected mice. In this review, an update of viral factors that are expressed during latency and their potential roles in regulating the latency-reactivation cycle is discussed. PMID:20169002

  1. DNA synthesis and DNA polymerase activity of herpes simplex virus type 1 temperature-sensitive mutants.

    PubMed Central

    Aron, G M; Purifoy, D J; Schaffer, P A

    1975-01-01

    Fifteen temperature-sensitive mutants of herpes simplex virus type 1 were studied with regard to the relationship between their ability to synthesize viral DNA and to induce viral DNA polymerase (DP) activity at permissive (34 C) and nonpermissive (39 C) temperatures. At 34 C, all mutants synthesized viral DNA, while at 39 C four mutants demonstrated a DNA+ phenotype, three were DNA+/-, and eight were DNA-. DNA+ mutants induced levels of DP activity similar to thhose of the wild-type virus at both temperatures, and DNA+/- mutants induced reduced levels of DP activity at 39 C but not at 34 C. Among the DNA- mutants three were DP+, two were DP+/-, and three showed reduced DP activity at 34 C with no DP activity at 39 C. DNA-, DP- mutants induced the synthesis of a temperature-sensitive DP as determined by in vivo studies. PMID:169388

  2. Restarting Lytic Gene Transcription at the Onset of Herpes Simplex Virus Reactivation.

    PubMed

    Cliffe, Anna R; Wilson, Angus C

    2017-01-15

    Herpes simplex virus (HSV) establishes a latent reservoir in neurons of human peripheral nerves. In this quiescent state, the viral genome persists as a circular, histone-associated episome, and transcription of viral lytic cycle genes is largely suppressed through epigenetic processes. Periodically, latent virus undergoes reactivation whereby lytic genes are activated and viral replication occurs. In this Gem, we review recent evidence that mechanisms governing the initial transcription of lytic genes are distinct from those of de novo infection and directly link reactivation to neuronal stress response pathways. We also discuss evidence that lytic cycle gene expression can be uncoupled from the full reactivation program, arguing for a less sharply bimodal definition of latency.

  3. Towards an understanding of the herpes simplex virus type 1 latency-reactivation cycle.

    PubMed

    Perng, Guey-Chuen; Jones, Clinton

    2010-01-01

    Infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system. Recurrent ocular shedding can lead to corneal scarring and vision loss making HSV-1 a leading cause of corneal blindness due to an infectious agent. The primary site of HSV-1 latency is sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease. During latency, the latency-associated transcript (LAT) is abundantly expressed. LAT expression is important for the latency-reactivation cycle in animal models, in part, because it inhibits apoptosis, viral gene expression, and productive infection. A novel transcript within LAT coding sequences (AL3) and small nonprotein coding RNAs are also expressed in trigeminal ganglia of latently infected mice. In this review, an update of viral factors that are expressed during latency and their potential roles in regulating the latency-reactivation cycle is discussed.

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

    PubMed

    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.

  5. Asymptomatic Herpes Simplex Virus Infection in Iranian Mothers and Their Newborns.

    PubMed

    Tavakoli, Ahmad; Monavari, Seyed Hamidreza; Bokharaei-Salim, Farah; Mollaei, Hamidreza; Abedi-Kiasari, Bahman; Fallah, Fatemeh Hoda; Mortazavi, Helya Sadat

    2017-02-01

    This study aims to determine the prevalence of herpes simplex virus (HSV) infection among pregnant women as well as congenital infection of their newborns in Tehran. One hundred samples of blood sera from pregnant women were analyzed for the presence of HSV specific antibodies. Umbilical cord blood samples from the newborns were analyzed for the presence of HSV DNA using real-time PCR. HSV IgG and IgM antibodies were found in 97% and 2% of pregnant women, respectively. Of all the 100 cord blood samples, 6 were positive for HSV DNA in which 2 cases were from mothers who had detectable IgM. It was notable that all corresponding mothers of six HSV positive infants had detectable IgG antibodies in their sera. It was demonstrated that the presence of HSV DNA in cord blood of newborns could be a risk marker for maternal-fetal transmission of the virus in asymptomatic pregnant women.

  6. Hypomethylation of host cell DNA synthesized after infection or transformation of cells by herpes simplex virus

    SciTech Connect

    Macnab, J.C.M.; Adams, R.L.P.; Rinaldi, A.; Orr, A.; Clark, L.

    1988-04-01

    Infection of rat embryo cells with herpes simplex virus type 2 caused undermethylation of host cell DNA synthesized during infection. DNA made prior to infection was not demethylated, but some of its degradation products, including methyl dCMP, were incorporated into viral DNA. The use of mutant virus showed that some viral DNA synthesis appears to be required for the inhibition of methylation. Inhibition of methylation cannot be explained by an absence of DNA methyltransferase as the activity of this enzyme did not change during the early period of infection. Inhibition of host cell DNA methylation may be an important step in the transformation of cells by herpesviruses, and various transformed cell lines tested showed reduced levels of DNA methylation.

  7. High Efficiency Latency and Activation of Herpes Simplex Virus in Human Cells

    NASA Astrophysics Data System (ADS)

    Wigdahl, Brian L.; Scheck, Adrienne C.; de Clercq, Erik; Rapp, Fred

    1982-09-01

    Herpes simplex virus (HSV) exists in humans in a latent form that can be activated. To characterize the molecular basis of the cell-virus interactions and to analyze the state of the latent HSV genome, an in vitro model system was established. In this system a large fraction of the latently infected cells contain an HSV genome that can be activated. Cell survival was reduced minimally after repression of high multiplicity HSV type 1 (HSV-1) infection of human fibroblast cells with (E)-5-(2-bromovinyl)-2'-deoxyuridine in combination with human leukocyte interferon (IFN-α ). A minimum of 1 to 3 percent of the surviving cells contained an HSV genome that could be activated either by human cytomegalovirus superinfection or reduction in incubation temperature.

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

    PubMed

    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.

  9. Systemic therapy of spontaneous prostate cancer in transgenic mice with oncolytic herpes simplex viruses.

    PubMed

    Varghese, Susan; Rabkin, Samuel D; Nielsen, G Petur; MacGarvey, Usha; Liu, Renbin; Martuza, Robert L

    2007-10-01

    Oncolytic viruses are an innovative therapeutic strategy for cancer, wherein viral replication and cytotoxicity are selective for tumor cells. Here we show the efficacy of systemically administered oncolytic viruses for the treatment of spontaneously arising tumors, specifically the use of oncolytic herpes simplex viruses (HSV) administered i.v. to treat spontaneously developing primary and metastatic prostate cancer in the transgenic TRAMP mouse, which recapitulates human prostate cancer progression. Four administrations of systemically delivered NV1023 virus, an HSV-1/HSV-2 oncolytic recombinant, to TRAMP mice at 12 or 18 weeks of age (presence of prostate adenocarcinoma or metastatic disease, respectively) inhibited primary tumor growth and metastases to lymph nodes. Expression of interleukin 12 (IL-12) from NV1042 virus, a derivative of NV1023, was additionally effective, significantly reducing the frequency of development of prostate cancer and lung metastases, even when the mice were treated after the onset of metastasis at 18 weeks of age. NV1042-infected cells, as detected by 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside staining for Lac Z expressed by the virus, were present in prostate tumors 1 week after the final virus injection and viral DNA was detected at 2 weeks after final virus injection by real-time PCR in primary and metastatic tumors but not in liver or blood. No toxicity was observed in any of the treated mice. The efficacy of the IL-12-expressing NV1042 virus in this aggressive prostate cancer model using a clinically relevant treatment paradigm merits its consideration for clinical studies.

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

    PubMed

    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.

  11. Recombinant Listeria monocytogenes expressing an immunodominant peptide fails to protect after intravaginal challenge with herpes simplex virus-2

    PubMed Central

    Muller, William J.; Orgun, Nural N.; Dong, Lichun; Koelle, David M.; Huang, Meei-Li; Way, Sing Sing

    2009-01-01

    Recombinant Listeria monocytogenes expressing a type-common herpes simplex virus (HSV) gB-peptide was shown previously to protect against footpad inoculation with HSV-1. We tested this construct for protection against vaginal challenge with HSV-2. Primed mice demonstrated strong recall responses, had modest reductions in HSV-2 DNA in vaginal mucosa, but were not protected from disease. PMID:18443737

  12. Comparison of the anti-herpes simplex virus activities of propolis and 3-methyl-but-2-enyl caffeate.

    PubMed

    Amoros, M; Lurton, E; Boustie, J; Girre, L; Sauvager, F; Cormier, M

    1994-05-01

    The in vitro activity against herpes simplex virus type 1 of 3-methyl-but-2-enyl caffeate isolated from poplar buds or prepared by synthesis was investigated. Under conditions of one or multiple multiplication cycles, this compound, which is a minor constituent of propolis, was found to reduce the viral titer by 3 log10, and viral DNA synthesis by 32-fold.

  13. Herpes virus infection and uterine cervix carcinoma. General considerations, personal experimental data and suggestions for a specific antiherpes adjuvant therapy.

    PubMed

    Nastac, E; Hozoc, M; Stoian, M

    1982-01-01

    The authors review some data of the literature and results of personal investigations that point out a relationship between human herpes simplex virus infection and the etiopathogeny of uterine cervix carcinoma. On the ground of these data the authors suggest a "specific antiherpes" adjuvant therapy in this form of human cancer.

  14. [The results of research conducted at the Stefan S. Nicolau Institute of Virology on the herpes simplex virus].

    PubMed

    Muţiu, A

    1989-01-01

    The report is a review of the research and results of the "Stefan S. Nicolau" Institute of Virology scientists in the field of herpes viruses, as they were materialized in the great number of published or communicated scientific papers these last ten years.

  15. Aphidicolin resistance in herpes simplex virus type 1 appears to alter substrate specificity in the DNA polymerase

    SciTech Connect

    Hall, J.D.; Woodward, S.

    1989-06-01

    The authors describe novel mutants of herpes simplex virus which are resistant to aphidicolin. Their mutant phenotypes suggest that they encode DNA polymerases with altered substrate recognition. This conclusion is based on their abnormal sensitivity to polymerase inhibitors and to the abnormal mutation rates exhibited by two of the mutants.

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

    PubMed

    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.

  17. Repression of host RNA polymerase II transcription by herpes simplex virus type 1.

    PubMed Central

    Spencer, C A; Dahmus, M E; Rice, S A

    1997-01-01

    Lytic infection of mammalian cells with herpes simplex virus type 1 (HSV-1) results in rapid repression of host gene expression and selective activation of the viral genome. This transformation in gene expression is thought to involve repression of host transcription and diversion of the host RNA polymerase (RNAP II) transcription machinery to the viral genome. However, the extent of virus-induced host transcription repression and the mechanisms responsible for these major shifts in transcription specificities have not been examined. To determine how HSV-1 accomplishes repression of host RNAP II transcription, we assayed transcription patterns on several cellular genes in cells infected with mutant and wild-type HSV-1. Our results suggest that HSV-1 represses RNAP II transcription on most cellular genes. However, each cellular gene we examined responds differently to the transcription repressive effects of virus infection, both quantitatively and with respect to the involvement of viral gene products. Virus-induced shutoff of host RNAP II transcription requires expression of multiple immediate-early genes. In contrast, expression of delayed-early and late genes and viral DNA replication appear to contribute little to repression of host cell RNAP II transcription. Modification of RNAP II to the intermediately phosphorylated (II(I)) form appears unlinked to virus-induced repression of host cell transcription. However, full repression of host transcription is correlated with depletion of the hyperphosphorylated (IIO) form of RNAP II. PMID:9032335

  18. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB.

    PubMed

    Zheng, Kai; Chen, Maoyun; Xiang, Yangfei; Ma, Kaiqi; Jin, Fujun; Wang, Xiao; Wang, Xiaoyan; Wang, Shaoxiang; Wang, Yifei

    2014-04-18

    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.

  19. Achalasia is not associated with measles or known herpes and human papilloma viruses.

    PubMed

    Birgisson, S; Galinski, M S; Goldblum, J R; Rice, T W; Richter, J E

    1997-02-01

    Achalasia is an esophageal motility disorder of unknown etiology. Several studies suggest possible herpes or measles virus etiology, but results are inconclusive. The aim of this study was to test whether herpesvirus (HV), measles (MV), or human papilloma virus (HPV) sequences could be detected in myotomy specimens from a wide spectrum of achalasia patients, using the polymerase chain reaction (PCR) technique. Myotomy specimens from 13 achalasia patients, esophagectomy specimens from nine esophageal cancer patients, and autopsy specimens from six fetuses were studied with the PCR technique. Paired oligonucleotide primers of HV (HSV-1 and 2, CMV, EBV, VZV, and HHV-6), MV and HPV sequences and exon 3 of the HPRT gene were used for the PCR DNA amplification. Amplified products were resolved on agarose gels and stained with ethidium bromide. All specimens yielded the appropriate-sized products for exon 3 of the HPRT and viral controls. No amplified products were seen in the achalasia specimens or controls corresponding to any of the virus sequences tested. The absence of HV, MV, and HPV sequences suggests that these viruses are not associated with achalasia but does not exclude the possibility of a previously unidentified virus as a causal agent. Further studies aimed at identifying an unknown viral agent as a cause for achalasia are warranted.

  20. Antiviral Effects of Blackberry Extract Against Herpes Simplex Virus Type 1

    PubMed Central

    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