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a mutation in the dna polymerase accessory factor of herpes simplex virus 1 restores viral dna replication in the presence of raltegravir.previous reports showed that raltegravir, a recently approved antiviral compound that targets hiv integrase, can inhibit the nuclease function of human cytomegalovirus (hcmv terminase) in vitro. in this study, subtoxic levels of raltegravir were shown to inhibit the replication of four different herpesviruses, herpes simplex virus 1 (hsv-1), hsv-2, hcmv, and mouse cytomegalovirus, by 30- to 700-fold, depending on the dose and the virus tested. southern blotting and quantitative pcr revealed that ...201425008933
genital infection with herpes simplex virus types 1 and 2 in women from natal, brazil.objective. to evaluate the prevalence of hsv-1 and hsv-2 in pregnant and nonpregnant women, testing the correlation between dna of the viruses with colposcopic and/or cytological changes, and evaluate association with sociodemographic characteristics and sexual activity. methods. included in this study were 106 pregnant and 130 nonpregnant women treated at primary health care units of natal, brazil, in the period 2010-2011. the patients were examined by colposcopy, and two cervical specimens wer ...201425006480
progressive outer retinal necrosis secondary to herpes simplex virus type 2.progressive outer retinal necrosis is an aggressive form of necrotizing herpetic retinitis that presents in immunocompromised patients. it is usually secondary to varicella zoster virus or, rarely, herpes simplex virus type 1. the authors report a case of progressive outer retinal necrosis associated with herpes simplex virus type 2 in a patient with a history of congenital herpes. [ophthalmic surg lasers imaging retina. 2014;45:xxx-xxx.].201424988530
hiv integrase inhibitors block replication of alpha-, beta-, and gammaherpesviruses.the catalytic site of the hiv integrase is contained within an rnase h-like fold, and numerous drugs have been developed that bind to this site and inhibit its activity. herpes simplex virus (hsv) encodes two proteins with potential rnase h-like folds, the infected cell protein 8 (icp8) dna-binding protein, which is necessary for viral dna replication and exhibits recombinase activity in vitro, and the viral terminase, which is essential for viral dna cleavage and packaging. therefore, we hypoth ...201424987091
prevalence of herpes simplex virus 1 and 2 antibodies in patients with autism spectrum disorders.the etiology of autism spectrum disorder (asd) is unknown, even though it is hypothesized that a viral infection could trigger this disorder. the aim of this study was to evaluate the seropositivity rate and antibody level of herpes simplex virus 1 (hsv1) and herpes simplex virus 2 (hsv2) in children with asd compared to same-aged healthy controls.201424982239
[herpes simplex virus type 2 fulminant hepatitis after umbilical cord blood transplantation for acute myeloid leukemia].this report describes a 41-year-old patient, who developed herpes simplex virus type 2 (hsv-2)-hepatitis after umbilical cord blood transplantation (cbt). the patient had received allogeneic bone marrow transplantation from an unrelated donor for acute myeloid leukemia (aml) not in remission. aml relapsed 18 months after the first transplantation, and cbt was performed. aml relapsed again 5 months later and the patient was given chemotherapy. although there was no active chronic graft-versus-hos ...201424975337
herpes simplex virus type 2 glycoprotein h interacts with integrin αvβ3 to facilitate viral entry and calcium signaling in human genital tract epithelial cells.herpes simplex virus (hsv) entry requires multiple interactions at the cell surface and activation of a complex calcium signaling cascade. previous studies demonstrated that integrins participate in this process, but their precise role has not been determined. these studies were designed to test the hypothesis that integrin αvβ3 signaling promotes the release of intracellular calcium (ca2+) stores and contributes to viral entry and cell-to-cell spread. transfection of cells with small interferin ...201424942591
commentary on "hsv-1 and hsv-2 seroprevalence in the united states among asymptomatic women unaware of any herpes simplex virus infection (herpevac trial for women)". 201424926672
hsv-1 and hsv-2 seroprevalence in the united states among asymptomatic women unaware of any herpes simplex virus infection (herpevac trial for women).recent evidence suggests that the epidemiology of herpes simplex viruses (hsvs) is changing because fewer hsv-1 infections are acquired in childhood and increased sexual transmission of hsv-1 is reported. the objective of the study was to assess the seroprevalence of type-specific antibodies to hsv-1 and hsv-2 in the united states.201424926671
evolutionary origins of human herpes simplex viruses 1 and 2.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 p ...201424916030
successful differentiation of herpes zoster-associated erythema multiforme from generalized extension of herpes by rapid polymerase chain reaction analysis.the polymerase chain reaction (pcr) assay for varicella zoster virus (vzv), herpes simplex virus (hsv)-1 and hsv-2 is available for use. sometimes the differential diagnosis of the generalized herpes zoster (hz), hsv1/2, and drug eruption is difficult. we report a case of hz followed by the vesicular erythema multiforme (em)-like lesion. in this case the use of pcr was of great assistance. a 78-year-old japanese man without any significant previous history of disease was admitted to our hospital ...201424909215
premature newborns with fatal intrauterine herpes simplex virus-1 infection: first report of twins and review of the literature.neonates with blistering skin diseases are dermatologic emergencies. the pathologies involved can pose diagnostic difficulties and there exists a variety of potential life-threatening differential diagnoses.201524909064
diagnosis of genital herpes simplex virus infection in the clinical laboratory.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 ...201424885431
population-based surveillance of neonatal herpes simplex virus infection in australia, 1997-2011.neonatal herpes simplex virus (hsv) infection is uncommon, but mortality after disseminated disease and morbidity after encephalitis are high. for the last decade, increased dose and duration of acyclovir has been advised to prevent disease progression and recurrence. we sought to determine prospectively the epidemiologic, clinical, and secular trends of this condition in australia.201424846638
detection of herpes simplex and varicella-zoster virus in clinical specimens by multiplex real-time pcr and melting curve analysis.herpes simplex viruses types 1 and 2 (hsv-1 and hsv-2), and varicella-zoster virus (vzv) are common agents resulting in various forms of clinical manifestation from skin vesicle to disseminated viral infection. the aim of the present study was to develop a real-time pcr and melting curve analysis which detect and differentiate hsv-1, hsv-2, and vzv, to compare with pcr-rflp using clinical specimens, and to introduce the 4-year experience in the clinical laboratory. three pairs of primers for hsv ...201424822189
antiherpesvirus activities of two novel 4'-thiothymidine derivatives, kay-2-41 and kah-39-149, are dependent on viral and cellular thymidine kinases.the emergence of drug-resistant herpesviruses represents a significant problem in clinical practice, primarily in immunocompromised patients. furthermore, effective antiviral therapies against gammaherpesvirus-associated diseases are lacking. here, we present two thiothymidine derivatives, kay-2-41 and kah-39-149, with different spectra of antiviral activity from those of the reference antiherpetic drugs, showing inhibitory activities against herpes simplex virus, varicella-zoster virus (vzv), a ...201424820089
associations of hla-a, hla-b and hla-c alleles frequency with prevalence of herpes simplex virus infections and diseases across global populations: implication for the development of an universal cd8+ t-cell epitope-based vaccine.a significant portion of the world's population is infected with herpes simplex virus type 1 and/or type 2 (hsv-1 and/or hsv-2), that cause a wide range of diseases including genital herpes, oro-facial herpes, and the potentially blinding ocular herpes. while the global prevalence and distribution of hsv-1 and hsv-2 infections cannot be exactly established, the general trends indicate that: (i) hsv-1 infections are much more prevalent globally than hsv-2; (ii) over a half billion people worldwid ...201424798939
frequency and abundance of alphaherpesvirus dna in human thoracic sympathetic ganglia.alphaherpesvirus reactivation from thoracic sympathetic ganglia (tsg) and transaxonal spread to target organs cause human visceral disease. yet alphaherpesvirus latency in tsg has not been well characterized. in this study, quantitative pcr detected varicella-zoster virus (vzv), herpes simplex virus 1 (hsv-1), and hsv-2 dna in 117 fresh tsg obtained postmortem from 15 subjects. vzv dna was found in 76 (65%) ganglia from all subjects, hsv-1 dna was found in 5 (4%) ganglia from 3 subjects, and no ...201424789785
pharmacokinetics-pharmacodynamics of the helicase-primase inhibitor pritelivir following treatment of wild-type or pritelivir-resistant virus infection in a murine herpes simplex virus 1 infection model.herpes simplex virus (hsv) infections can cause considerable morbidity. transmission of hsv-2 has become a major health concern, since it has been shown to promote transmission of other sexually transmitted diseases. pritelivir (aic316, bay 57-1293) belongs to a new class of hsv antiviral compounds, the helicase-primase inhibitors, which have a mode of action that is distinct from that of antiviral nucleoside analogues currently in clinical use. analysis of pharmacokinetic-pharmacodynamic parame ...201424752278
[anti-herpetic effect of photodynamic action in an in vitro experiment].evaluation of photodynamic therapy (pdt) in vitro antiviral effect directly on the herpes simplex virus (hsv) as well as on virus infected cells.201424738294
detection and differentiation of herpes simplex viruses by use of the viper platform: advantages, limitations, and concerns.the viper hsv-q(x) assay was evaluated for the detection of herpes simplex virus 1 (hsv-1) and hsv-2 in specimens from oral, anogenital, and other miscellaneous sites. the hsv-q(x) assay was found to be highly sensitive and accurate; however, a gray zone may be required for specimens with values falling between 50 and 800 maximum relative fluorescence units.201424696023
broadly reactive human cd8 t cells that recognize an epitope conserved between vzv, hsv and ebv.human herpesviruses are important causes of potentially severe chronic infections for which t cells are believed to be necessary for control. in order to examine the role of virus-specific cd8 t cells against varicella zoster virus (vzv), we generated a comprehensive panel of potential epitopes predicted in silico and screened for t cell responses in healthy vzv seropositive donors. we identified a dominant hla-a*0201-restricted epitope in the vzv ribonucleotide reductase subunit 2 and used a te ...201424675761
herpes simplex virus growth, preparation, and assay.in order to study the biology of herpes simplex virus or to use it as a vector in gene therapy, it is necessary to grow the virus and to prepare virus stocks. many different protocols are available from different research groups working with herpes simplex virus type 1 or 2 (hsv-1 or hsv-2). this chapter describes the procedures used in our laboratory.201424671674
better neutralization of herpes simplex virus type 1 (hsv-1) than hsv-2 by antibody from recipients of glaxosmithkline hsv-2 glycoprotein d2 subunit vaccine.the herpevac trial evaluated a herpes simplex virus type 2 (hsv-2) glycoprotein d (gd2) subunit vaccine to prevent genital herpes. unexpectedly, the vaccine protected against genital hsv-1 infection but not genital hsv-2 infection. we evaluated sera from 30 women seronegative for hsv-1 and hsv-2 who were immunized with gd2 in the herpevac trial. neutralizing antibody titers to hsv-1 were 3.5-fold higher than those to hsv-2 (p < .001). hsv-2 gc2 and ge2 on the virus blocked neutralization by gd2 ...201424652496
functional characterization of ocular-derived human alphaherpesvirus cross-reactive cd4 t cells.intraocular varicella-zoster virus (vzv) and hsv type 1 (hsv-1) infections cause sight-threatening uveitis. the disease is characterized by an intraocular inflammatory response involving herpesvirus-specific t cells. t cell reactivity to the noncausative human alphaherpesvirus (αhhv) is commonly detected in the affected eyes of herpetic uveitis patients, suggesting the role of cross-reactive t cells in the disease. this study aimed to identify and functionally characterize intraocular human alph ...201424623134
epidemiology of genital herpes simplex virus type 1 and 2 infections in southwestern finland during a 10-year period (2003-2012).the objective of this study was to analyze the proportion of herpes simplex virus types 1 and 2 (hsv-1 and hsv-2) in genital infections during a 10-year period (2003-2012) among outpatients of a clinic of sexually transmitted disease in southwestern finland.201424622640
incidence and clinical features of herpes simplex viruses (1 and 2) and varicella-zoster virus infections in an adult korean population with aseptic meningitis or encephalitis.since there are limited data on the incidence and clinical findings of central nervous system (cns) infection by three α-herpesviruses including human herpes simplex virus 1 (hsv-1), hsv-2 and varicella-zoster virus (vzv) in korea, a retrospective analysis of clinical data and polymerase chain reaction (pcr) results was performed in patients who presented with suspicion of acute viral meningitis and/or encephalitis at the emergency department of a tertiary referral hospital in seoul, korea. duri ...201424610349
chemical characterization and antiherpes activity of sulfated polysaccharides from lithothamnion muelleri.we report herein the chemical characterization and antiherpes activity of polysaccharides from the red alga lithothamnion muelleri (hapalidiaceae). the polysaccharide-rich fractions b1 and b2 were obtained by extraction with na2co3 and were purified by size exclusion chromatography to afford fra-b1 and fra-b2. the polysaccharides were characterized by ft-ir and chemical analysis (total contents of carbohydrates, proteins, sulfate and uronic acid), whereas their average molecular weights were est ...201424608026
hsv-1 as well as hsv-2 is frequent in oral mucosal lesions of children on chemotherapy.prevalence data of herpes simplex virus (hsv) in oral mucositis in children on treatment for cancer is limited. quantitative polymerase chain reaction (pcr) has been seldom utilized for detection of hsv-1/2 in oral mucosa.201424522744
asymptomatic memory cd8+ t cells: from development and regulation to consideration for human vaccines and immunotherapeutics.generation and maintenance of high quantity and quality memory cd8(+) t cells determine the level of protection from viral, bacterial, and parasitic re-infections, and hence constitutes a primary goal for t cell epitope-based human vaccines and immunotherapeutics. phenotypically and functionally characterizing memory cd8(+) t cells that provide protection against herpes simplex virus type 1 and type 2 (hsv-1 and hsv-2) infections, which cause blinding ocular herpes, genital herpes, and oro-facia ...201424499824
binding of hsv-1 glycoprotein k (gk) to signal peptide peptidase (spp) is required for virus infectivity.glycoprotein k (gk) is a virion envelope protein of herpes simplex virus types 1 (hsv-1) and 2 (hsv-2), which plays important roles in virion entry, morphogenesis and egress. two-hybrid and pull-down assays were utilized to demonstrate that gk and no other hsv-1 genes specifically binds to signal peptide peptidase (spp), also known as minor histocompatibility antigen h13. spp dominant negative mutants, shrna against spp significantly reduced hsv-1 replication in vitro. spp also affected lysosome ...201424465545
antiretroviral therapy is not associated with reduced herpes simplex virus shedding in hiv coinfected adults: an observational cohort study.herpes simplex virus types 1 and 2 (hsv-1/2) may have adverse consequences on hiv type 1 infection. we quantified the frequency of hsv reactivations in highly active antiretroviral therapy (haart)-treated adults with hiv, and compared it with that in haart-naïve patients.201424464523
mimicking herpes simplex virus 1 and herpes simplex virus 2 mucosal behavior in a well-characterized human genital organ culture.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 entr ...201424436451
evaluation of commercial herpes simplex virus igg and igm enzyme immunoassays.serological methods are used widely for the determination of herpes simplex virus (hsv) igg and igm antibodies in virological laboratories. the present study evaluates the automated performance of the virion\serion (würzburg, germany) and orgentec (mainz, germany) enzyme-linked immunosorbent assays (elisa) for the determination of hsv type-common and type-specific igg and igm antibodies. two hundred sixty-three sera from hsv-negative children, healthy blood donors as well as patients without and ...201424418499
roles of conserved residues within the pre-nh2-terminal domain of herpes simplex virus 1 dna polymerase in replication and latency in mice.the catalytic subunit of the herpes simplex virus 1 dna polymerase (hsv-1 pol) is essential for viral dna synthesis and production of infectious virus in cell culture. while mutations that affect 5'-3' polymerase activity have been evaluated in animal models of hsv-1 infection, mutations that affect other functions of hsv-1 pol have not. in a previous report, we utilized bacterial artificial chromosome technology to generate defined hsv-1 pol mutants with lesions in the previously uncharacterize ...201424413420
development of biomarker panel to predict, prevent and create treatments tailored to the persons with human papillomavirus-induced cervical precancerous lesions.human papillomavirus (hpv) induce many cancer conditions and cause cervical cancer, second in frequency of malignant disease in women.the aim was to develop biomarker panel for hpv-induced cervical precancerous diseases in patients infected with herpes simplex virus (hsv).201424386936
pathological role of regulatory t cells in the initiation and maintenance of eczema herpeticum lesions.it remains unknown why the occurrence of eczema herpeticum (eh) caused by an extensive disseminated cutaneous infection with hsv-1 or hsv-2 is associated with the exacerbation of atopic dermatitis lesions after withdrawal of treatment. although regulatory t cells (tregs) limit the magnitude of hsv-specific t cell responses in mice, their role in the induction and resolution of eh has not been defined. we initially investigated the frequencies, phenotype, and function of tregs in the peripheral b ...201424379126
[ocular hypertension in herpes simplex keratouveitis].the herpes simplex virus is one of the most common pathogens in humans, who are seropositive for the virus in 90% of the cases at the adult age. it determines reccurent infections in more than a third of the population and these infections depend on the immune response of the host. ocular infections of newborns are due to the herpes simplex virus type 2, meanwhile type 1 is found predominantly at adults; almost all ocular structures can be affected. hsv-1 in the most frequent etiologic agent in ...201425842621
immunogenic hsv-mediated oncolysis shapes the antitumor immune response and contributes to therapeutic efficacy.within the oncolytic virus field, the extent of virus replication that is essential for immune stimulation to control tumor growth remains unresolved. using infected cell protein 0 (icp0)-defective oncolytic herpes simplex virus type 1 (hsv-1) and hsv-2 viruses (dicp0 and dnls) that show differences in their in vitro replication and cytotoxicity, we investigated the inherent features of oncolytic hsv viruses that are required for potent antitumor activity. in vitro, the hsv-2 vectors showed rapi ...201424343053
evaluation of antiviral activities of four local malaysian phyllanthus species against herpes simplex viruses and possible antiviral target.nucleoside analogues such as acyclovir are effective antiviral drugs against herpes simplex virus infections since its introduction. however, with the emergence of acyclovir-resistant hsv strains particularly in immunocompromised patients, there is a need to develop an alternative antiherpetic drug and plants could be the potential lead. in this study, the antiviral activity of the aqueous extract of four phyllanthus species were evaluated against herpes simplex virus type-1 (hsv-1) and hsv-2 in ...201324324358
a paradigm shift: vaccine-induced antibodies as an immune correlate of protection against herpes simplex virus type 1 genital herpes. 201424285847
protection provided by a herpes simplex virus 2 (hsv-2) glycoprotein c and d subunit antigen vaccine against genital hsv-2 infection in hsv-1-seropositive guinea pigs.a prophylactic vaccine for genital herpes disease remains an elusive goal. we report the results of two studies performed collaboratively in different laboratories that assessed immunogenicity and vaccine efficacy in herpes simplex virus 1 (hsv-1)-seropositive guinea pigs immunized and subsequently challenged intravaginally with hsv-2. in study 1, hsv-2 glycoproteins c (gc2) and d (gd2) were produced in baculovirus and administered intramuscularly as monovalent or bivalent vaccines with cpg and ...201424284325
the etiology of infectious proctitis in men who have sex with men differs according to hiv status.we compared the spectrum of pathogens responsible for infectious proctitis between hiv-positive and hiv-negative men who have sex with men. only 32% of men with herpes simplex virus (hsv)-associated proctitis had visible external anal ulceration.the etiology of infectious proctitis among hiv-positive and hiv-negative men is as follows: chlamydia (23.4% vs. 21.7%, p = 0.7), gonorrhea (13.4% vs. 10.8%, p = 0.5), hsv-1 (14.2% vs. 6.5%, p = 0.04), hsv-2 (22% vs. 12.3%, p = 0.03), lymphogranuloma ven ...201324275725
generation of “lymph node derived antibody libraries” (lyndal) for selecting fully human antibody fragments with therapeutic potential.the development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. here, we present a methodology for recovering such antibodies from antigen-encountered human b cell repertoires. as the source for variable antibody genes, we cloned immunoglobulin g (igg)-derived b cell repertoires from lymph nodes of 20 individuals underg ...201724256717
the synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker.the efficient synthesis of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker is described starting from diethyl azidomethyl-, 2-azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropyl- and 3-azido-1-hydroxypropylphosphonates and selected alkynes under microwave irradiation. several o,o-diethylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. all compounds were evaluated in vitro for activity against a b ...201324219992
evaluation of pd 404,182 as an anti-hiv and anti-herpes simplex virus microbicide.pd 404,182 (pd) is a synthetic compound that was found to compromise hiv integrity via interaction with a nonenvelope protein viral structural component (a. m. chamoun et al., antimicrob. agents chemother. 56:672-681, 2012). the present study evaluates the potential of pd as an anti-hiv microbicide and establishes pd's virucidal activity toward another pathogen, herpes simplex virus (hsv). we show that the anti-hiv-1 50% inhibitory concentration (ic50) of pd, when diluted in seminal plasma, is ∼ ...201424217696
plasmacytoid dendritic cells contribute to systemic but not local antiviral responses to hsv infections.plasmacytoid dendritic cells (pdc) produce type i interferons (ifn-i) and proinflammatory cytokines in response to viruses; however, their contribution to antiviral immunity in vivo is unclear. in this study, we investigated the impact of pdc depletion on local and systemic antiviral responses to herpes simplex virus (hsv) infections using clec4c-dtr transgenic mice. we found that pdc do not appear to influence viral burden or survival after vaginal hsv-2 infection, nor do they seem to contribut ...201324204273
development and clinical validation of a multiplex real-time pcr assay for herpes simplex and varicella zoster virus.herpes simplex virus (hsv) and varicella zoster virus (vzv) are related members of the herpesviridae family and are well-documented human pathogens causing a spectrum of diseases, from mucocutaneous disease to infections of the central nervous system. this study was carried out to evaluate and validate the performance of a multiplex real-time polymerase chain reaction (pcr) assay in detecting and differentiating hsv1, hsv2, and vzv from clinical samples. consensus pcr primers for hsv were design ...201324193006
single dose of glycoprotein k (gk)-deleted hsv-1 live-attenuated virus protects mice against lethal vaginal challenge with hsv-1 and hsv-2 and induces lasting t cell memory immune responses.herpes simplex virus type-1(hsv-1) and hsv-2 are important human pathogens that cause significant ocular and urogenital complications, respectively. we have previously shown that hsv-1 virions lacking glycoprotein k (gk) are unable to enter into neurons via synaptic axonal membranes and be transported in either retrograde or anterograde manner. here, we tested the ability of hsv-1 (f) gk-null to protect against lethal challenge with either highly virulent ocular hsv-1 (mckrae strain), or genital ...201324165088
antiherpetic effects of gynura procumbens.the ethanol extract of gynura procumbens showed virucidal and antireplicative actions against herpes simplex virus hsv-1 and hsv-2. it was further chromatographed on mci gel chp20p column giving the extract fractions f1 (water), f2 (water-methanol) f3 (methanol), and f4 (ethyl acetate). all but f1 had virucidal action against both viral types. we reported here the active compounds from f2 and f3. the antiherpetic compounds of f2 was a mixture of dicaffeoylquinic acids with virucidal and antirepl ...201324159345
herpes simplex virus drug-resistance: new mutations and insights.acyclovir (acv) is the first-line treatment for the management of herpes simplex virus 1 (hsv-1) and 2 (hsv-2) diseases. long-term administration of the drug for the treatment of chronic infections in the immunocompromised host can lead to the development of acv-resistance. this review provides an update of the mutations linked to drug-resistance and issues to be considered in the management of hsv infections refractory to antiviral therapy.201324152761
update on herpes virus infections of the nervous system.herpes simplex viruses types 1 and 2 (hsv-1 and hsv-2) are human neurotropic viruses that establish latent infection in dorsal root ganglia (drg) for the entire life of the host. from the drg they can reactivate to cause human morbidity and mortality. although they vary, in part, in the clinical disorders they cause, and in their molecular structure, they share several features that govern the biology of their infection of the human nervous system. hsv-1 is the causative agent of encephalitis, c ...201324142852
the scarlet h. 201424136793
seroprevalence of herpes simplex virus types 1 and 2--united states, 1999-2010.herpes simplex virus types 1 and 2 (hsv-1 and hsv-2) are common infections with serious sequelae. hsv-1 is an increasingly important cause of genital herpes in industrialized countries.201424136792
seropositivity to herpes simplex virus type 2, but not type 1 is associated with premature cardiovascular diseases: a population-based cross-sectional study.thirty-five years after herpesviruses were suggested to induce atherosclerosis sero-epidemiological evidence on herpes simplex viruses (hsv) remains sparse and controversial. we aimed to investigate the relationship between hsv-1 and hsv-2 infections and cardiovascular diseases (cvd).201324125404
structural basis for the antibody neutralization of herpes simplex virus.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 ...201324100313
analysis of compounds that interfere with herpes simplex virus-host receptor interactions using surface plasmon resonance.the entry of herpes simplex virus into host cells involves a complex series of events that require concerted inputs from multiple hsv glycoproteins. among these glycoproteins, the gd protein of hsv-1 and hsv-2 plays an important role for host receptor binding and membrane fusion. in the present study, we evaluated the ability of different sulfated saccharides to interfere with gd-host receptor (hvem) interactions using our recently reported molecular assay (gopinath, s. c. b.; hayashi, k.; kumar ...201324079703
surveillance of herpes simplex virus resistance to antivirals: a 4-year survey.herpes simplex virus (hsv) resistance to antivirals constitutes a therapeutic challenge, especially among immunocompromised patients. this observational survey on hsv resistance to antivirals was conducted retrospectively over a 4-year period (2008-2012). a total of 211 hsv-positive clinical samples (94 hsv-1 and 117 hsv-2) recovered from 139 patients (11 immunocompetent patients, 85 immunocompromised patients, and 43 patients with unknown immune status) with suspected hsv drug-resistance were a ...201324075863
topical application of polyethylenimine as a candidate for novel prophylactic therapeutics against genital herpes caused by herpes simplex virus.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 ag ...201424046087
[laboratory diagnosis of genital herpes--direct immunofluorescence method].aim of the study was to determine clinical usefulness of direct immunofluorescence method in the laboratory diagnosis of genital herpes in women.201324032273
comparison of simplexa hsv 1 & 2 pcr with culture, immunofluorescence, and laboratory-developed taqman pcr for detection of herpes simplex virus in swab specimens.the simplexa hsv 1 & 2 direct pcr assay was compared with conventional cell culture, cytospin-enhanced direct fluorescent antibody (dfa), and a laboratory-developed real-time taqman pcr (ldt hsv pcr) using extracted nucleic acid for the detection of herpes simplex virus (hsv) in dermal, genital, mouth, ocular, and other swab samples. one hundred seventy-one swabs were tested prospectively, and 58 were positive for hsv (34 hsv-1 and 24 hsv-2). cytospin-dfa detected 50 (86.2%), conventional cell c ...201324006008
silicone-acyclovir controlled release devices suppress primary herpes simplex virus-2 and varicella zoster virus infections in vitro.following initial infection, herpesviruses retreat into a permanent latent state with periodic reactivation resulting in an enhanced likelihood of transmission and clinical disease. the nucleoside analogue acyclovir reduces clinical symptoms of the three human alpha herpesviruses, hsv-1, hsv-2, and vzv. long-term administration of acyclovir (acv) can reduce the frequency and severity of reactivation, but its low bioavailability and short half-life require a daily drug regimen. our lab is working ...201323983683
seroprevalence of hsv-1 and hsv-2 antibodies in canadian women screened for enrolment in a herpes simplex virus vaccine trial.herpes simplex virus 1 and 2 (hsv-1 and hsv-2) infections continue to be among the most common and unrecognized sexually transmitted infections in the world. although treatable, hsv-1 and hsv-2 infections remain incurable. hence, there is interest in the development of a vaccine to prevent genital herpes. as part of a multicentre, randomized, placebo-controlled trial to test such a vaccine, healthy women 18-30 years were enrolled as volunteers in several canadian centres between 2005 and 2007. t ...201323970700
molecular characterization of herpes simplex virus 2 strains by analysis of microsatellite polymorphism.the complete 154-kbp linear double-stranded genomic dna sequence of herpes simplex virus 2 (hsv-2), consisting of two extended regions of unique sequences bounded by a pair of inverted repeat elements, was published in 1998 and since then has been widely employed in a wide range of studies. throughout the hsv-2 genome are scattered 150 microsatellites (also referred to as short tandem repeats) of 1- to 6-nucleotide motifs, mainly distributed in noncoding regions. microsatellites are considered r ...201323966512
susceptibility of human placenta derived mesenchymal stromal/stem cells to human herpesviruses infection.fetal membranes (fm) derived mesenchymal stromal/stem cells (mscs) are higher in number, expansion and differentiation abilities compared with those obtained from adult tissues, including bone marrow. upon systemic administration, ex vivo expanded fm-mscs preferentially home to damaged tissues promoting regenerative processes through their unique biological properties. these characteristics together with their immune-privileged nature and immune suppressive activity, a low infection rate and you ...201323940750
herpes virus infection of the peripheral nervous system.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 an ...201323931801
herpes genitalis - topical zinc sulfate: an alternative therapeutic and modality.herpes genitalis is one of the commonest sexually transmitted infections in the world caused by herpes simplex virus (hsv) 1 and 2. all herpes viruses show latency. herpes genitalis caused by hsv-1 and hsv-2 is recurrent in 55 and 90% of case respectively.201323919052
antiviral agents for herpes simplex virus.this review starts with a brief description of herpes simplex virus types 1 and 2 (hsv-1 and hsv-2), the clinical diseases they cause, and the continuing clinical need for antiviral chemotherapy. a historical overview describes the progress from the early, rather toxic antivirals to acyclovir (acv) which led the way for its prodrug, valacyclovir, to penciclovir and its prodrug, famciclovir (fcv). these compounds have been the mainstay of hsv therapy for two decades and have established a remarka ...201323885997
zinc ionophores pyrithione inhibits herpes simplex virus replication through interfering with proteasome function and nf-κb activation.pyrithione (pt), known as a zinc ionophore, is effective against several pathogens from the streptococcus and staphylococcus genera. the antiviral activity of pt was also reported against a number of rna viruses. in this paper, we showed that pt could effectively inhibit herpes simplex virus types 1 and 2 (hsv-1 and hsv-2). pt inhibited hsv late gene (glycoprotein d, gd) expression and the production of viral progeny, and this action was dependent on zn(2+). further studies showed that pt suppre ...201323867132
application of shrna-containing herpes simplex virus type 1 (hsv-1)-based gene therapy for hsv-2-induced genital herpes.hsv-1-based vectors have been widely used to achieve targeted delivery of genes into the nervous system. in the current study, we aim to use shrna-containing hsv-1-based gene delivery system for the therapy of hsv-2 infection. guinea pigs were infected intravaginally with hsv-2 and scored daily for 100 days for the severity of vaginal disease. hsv-2 shrna-containing hsv-1 was applied intravaginally daily between 8 and 14 days after hsv-2 challenge. delivery of hsv-2 shrna-containing hsv-1 had no ...201323845900
pcr for detection of herpes simplex virus in cerebrospinal fluid: alternative acceptance criteria for diagnostic workup.the determination of herpes simplex virus (hsv) infection using a pcr assay is one of the most commonly requested tests for analysis of cerebrospinal fluid (csf), although only a very low proportion of results are positive. a previously reported study showed that selecting only those csf samples with >5 leukocytes/mm(3) or a protein level of >50 mg/dl was adequate for the diagnostic workup. the aim of the present study was to assess the reliability of alternative acceptance criteria based on ele ...201323804382
acute retinal necrosis in a neonate.to report an unusual case of dizygotic twins, in whom one neonate developed acute retinal necrosis from herpes simplex virus (hsv) type 2.201325383815
recent issues in herpes simplex encephalitis.herpes simplex encephalitis (hse) remains the most important cause of fatal sporadic encephalitis in man. caused by herpes simplex virus type 1 (hsv-1), and more rarely by hsv-2, it can have devastating clinical consequences for the patient, especially when the instigation of acyclovir therapy has been delayed by more than 2 days or more. even with acyclovir treatment, nearly a third of patients may die or suffer significant morbidity. both host and viral factors may interact to affect the clini ...201323775137
role of immediate early protein icp27 in the differential sensitivity of herpes simplex viruses 1 and 2 to leptomycin b.leptomycin b (lmb) is a highly specific inhibitor of crm1, a cellular karyopherin-β that transports nuclear export signal-containing proteins from the nucleus to the cytoplasm. previous work has shown that lmb blocks herpes simplex virus 1 (hsv-1) replication in vero cells and that certain mutations in viral immediate early protein icp27 can confer lmb resistance. however, little is known of the molecular mechanisms involved. here we report that hsv-2, a close relative of hsv-1, is naturally res ...201323740995
increased carotid intima-media thickness associated with antibody responses to varicella-zoster virus and cytomegalovirus in hiv-infected patients.we investigated the relationship of the herpesviridiae with inflammation and subclinical atherosclerosis in hiv-infected patients.201323717597
isolation of herpes simplex viruses by chick embryo culture.the chick embryo is a versatile host system in diagnostic virology, especially for isolation of herpes simplex viruses. in this study, samples obtained from 57 clinically diagnosed patients with active herpetic lesions (35 genital & 22 non-genital) were cultured by chick embryo method for isolation of herpes simplex virus. after inoculation onto the chorioallantoic membrane (cam) of 10-11 days old chick embryo, typical cam reactions (pocks) appeared in 23(40.3%) samples after 3 days. cam reactio ...201323715363
t-cell immunity to human alphaherpesviruses.human alphaherpesviruses (αhhv) - herpes simplex virus type 1 (hsv-1), hsv-2, and varicella-zoster virus (vzv) - infect mucosal epithelial cells, establish a lifelong latent infection of sensory neurons, and reactivate intermittingly to cause recrudescent disease. although chronic αhhv infections co-exist with brisk t-cell responses, t-cell immune suppression is associated with worsened recurrent infection. induction of αhhv-specific t-cell immunity is complex and results in poly-specific cd4 an ...201323664660
use of a comprehensive polymerase chain reaction system for diagnosis of ocular infectious diseases.to measure the genomic dna of ocular infectious pathogens in ocular fluids and to analyze the clinical relevance of these pathogens in uveitis and endophthalmitis.201323664179
the identities and anti-herpes simplex virus activity of clinacanthus nutans and clinacanthus siamensis.to distinguish the difference among the clinacanthus nutans (burm. f.) lindau (c. nutans) and clinacanthus siamensis bremek (c. siamensis) by assessing pharmacognosy characteristics, molecular aspect and also to evaluate their anti-herpes simplex virus (hsv) type 1 and type 2 activities.201323620852
herpes simplex virus type 2 coinfection does not accelerate cd4 count decline in untreated hiv infection.herpes simplex virus type 2 (hsv-2) reactivations are associated with increased hiv load, but whether hsv-2 coinfection accelerates hiv disease is unclear. we compared rates of cd4 count decline according to hsv-2 status in untreated hiv-infected adults.201323572481
overcoming drug-resistant herpes simplex virus (hsv) infection by a humanized antibody.despite the availability of antiviral chemotherapy, herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) infections remain a severe global health problem. of particular concern is the growing incidence of drug resistance in immunocompromised patients, which stresses the urgency to develop new effective treatment alternatives. we have developed a humanized monoclonal antibody (mab hu2c) that completely abrogates viral cell-to-cell spread, a key mechanism by which hsv-1/2 escapes humoral immune ...201323569258
current status of herpesvirus identification in the oral cavity of hiv-infected children.some viruses of the herpesviridae family are frequently the etiologic agents of oral lesions associated with hiv. the aim of this study was to identify the presence of herpes simplex virus types 1 and 2 (hsv-1, hsv-2), varicella zoster virus (vzv), epstein-barr virus (ebv), human cytomegalovirus (hcmv), human herpesvirus type 6, type 7 and type 8 (hhv-6, hhv-7 and hhv-8) in the oral cavity of hiv-infected children/adolescents and verify the association between viral subtypes and clinical factors ...201323563819
exhaustion, immuno-inflammation, and pathogen burden after cardiac surgery: an exploratory study.exhaustion, a consequence of prolonged stress characterized by unusual fatigue, is associated with increased risk of cardiac morbidity and mortality. in patients recovering from coronary artery bypass (cabg), little is known about the relationship of 1) immune-mediated inflammation and resultant endothelial activation, and 2) cumulative exposure to infectious pathogens (pathogen burden (pb)) implicated in coronary atherosclerosis to exhaustion.201423524631
different mechanisms regulate productive herpes simplex virus 1 (hsv-1) and hsv-2 infections in adult trigeminal neurons.herpes simplex virus 1 (hsv-1) and hsv-2 establish latency in different neuronal subtypes (a5+ and kh10+) in murine trigeminal ganglia, results which correlate with restricted productive infection in these neurons in vitro. hsv-2 latency-associated transcript (lat) contains a cis-acting regulatory element near the transcription start site that promotes productive infection in a5+ neurons and a second element in exon 1 that inhibits productive infection in kh10+ neurons. hsv-1 contains no such re ...201323514893
genome sequence of a chimpanzee herpesvirus and its relation to other primate alphaherpesviruses.this study reports the complete genome sequence of chimpanzee herpesvirus (chhv), an alphaherpesvirus isolated from a chimpanzee. although closely related to human herpes simplex virus type 2 (hsv2), the level of sequence diversity confirms that chhv is sufficiently distinct to be considered a member of a different virus species rather than a variant strain of hsv2. phylogenetic comparison with other simplexviruses at several levels supports the hypothesis that hsv2 and chhv co-evolved with thei ...201323508549
in vivo anti-herpes simplex virus activity of a sulfated derivative of agaricus brasiliensis mycelial polysaccharide.agaricus brasiliensis (syn. a. subrufescens), a basidiomycete fungus native to the atlantic forest in brazil, contains cell walls rich in glucomannan polysaccharides. the β-(1 → 2)-gluco-β-(1 → 3)-mannan was isolated from a. brasiliensis mycelium, chemically modified by sulfation, and named mi-s. mi-s has multiple mechanisms of action, including inhibition of herpes simplex virus (hsv) attachment, entry, and cell-to-cell spread (f. t. g. s. cardozo, c. m. camelini, a. mascarello, m. j. rossi, r. ...201323507287
the herpes simplex virus 2 ul21 protein is essential for virus propagation.herpes simplex virus 2 (hsv-2) is an important human pathogen that is the major cause of genital herpes infections and a significant contributor to the epidemic spread of human immunodeficiency virus infections. the ul21 gene is conserved throughout the alphaherpesvirinae subfamily and encodes a tegument protein that is dispensable for hsv-1 and pseudorabies virus replication in cultured cells; however, its precise functions have not been determined. to investigate the role of ul21 in the hsv-2 ...201323487471
herpes simplex virus 2 expresses a novel form of icp34.5, a major viral neurovirulence factor, through regulated alternative splicing.herpes simplex virus 1 (hsv-1) and hsv-2, two closely related neurotropic human herpesviruses, achieve neurotropism through icp34.5, a major viral neurovirulence factor. in this report, in addition to the full-length 38-kda protein (icp34.5α), we identified a 28-kda novel form of icp34.5 (icp34.5β) in hsv-2-infected cells. icp34.5β is translated from unspliced icp34.5 mrna, with the retained intron introducing a premature stop codon. thus, icp34.5β lacks the c-terminal conserved gadd34 domain bu ...201323487469
binding of transmembrane mucins to galectin-3 limits herpesvirus 1 infection of human corneal keratinocytes.epithelial cells lining mucosal surfaces impose multiple barriers to viral infection. at the ocular surface, the carbohydrate-binding protein galectin-3 maintains barrier function by cross-linking transmembrane mucins on the apical glycocalyx. despite these defense mechanisms, many viruses have evolved to exploit fundamental cellular processes on host cells. here, we use affinity assays to show that herpes simplex virus type 1 (hsv-1), but not hsv-2, binds human galectin-3. knockdown of galectin ...201323487460
high-purity preparation of hsv-2 vaccine candidate acam529 is immunogenic and efficacious in vivo.genital herpes is a sexually transmitted infection (sti) caused by herpes simplex virus 2 (hsv-2) and to a lesser extent herpes simplex virus 1 (hsv-1). infection by hsv-2 is life-long and is associated with significant cost to healthcare systems and social stigma despite the highly prevalent nature of the disease. for instance, the proportion of hsv-2 seropositive to seronegative adults is approximately 1 in 5 in the us and greater than 4 in 5 in some areas of sub-saharan africa. the replicatio ...201323468943
immunogenicity and safety of different formulations of an adjuvanted glycoprotein d genital herpes vaccine in healthy adults: a double-blind randomized trial.herpes simplex virus (hsv) type 2 (hsv-2) is the main cause of genital and neonatal herpes and is highly prevalent worldwide. previous phase i and ii studies showed the immunogenicity and safety of the candidate prophylactic hsv-2 glycoprotein d-based subunit vaccine (gd2-as04), containing aluminum hydroxide and 3-o-deacylated monophosphoryl lipid a (mpl) as adjuvant (as04), in healthy adults. the primary objective of the study presented here was to compare the immunogenicity and safety of five ...201323434737
dendrimers functionalized with membrane-interacting peptides for viral inhibition.this contribution reports the synthesis of a poly(amide)-based dendrimer functionalized at the termini with a membrane-interacting peptide derived from the herpes simplex virus (hsv) type 1 glycoprotein h, namely gh625-644. this peptide has been shown to interact with model membranes and to inhibit viral infectivity. the peptidodendrimer inhibits both hsv-1 and hsv-2 at a very early stage of the entry process, most likely through an interaction with the viral envelope glycoproteins; thus, preven ...201323429490
immune regulation of human herpesviruses and its implications for human transplantation.human herpesviruses including cytomegalovirus, epstein-barr virus, hhv6, hhv7, hhv8, herpes simplex virus (hsv)-1 and hsv-2 and varicella zoster virus (vzv) have developed an intricate relationship with the human immune system. this is characterized by the interplay between viral immune evasion mechanisms that promote the establishment of a lifelong persistent infection and the induction of a broad humoral and cellular immune response, which prevents the establishment of viral disease. understan ...201323347211
activity and mechanism of action of hdvd, a novel pyrimidine nucleoside derivative with high levels of selectivity and potency against gammaherpesviruses.a novel nucleoside analogue, 1-[(2s,4s-2-(hydroxymethyl)-1,3-dioxolan-4-yl]5-vinylpyrimidine-2,4(1h,3h)-dione, or hdvd, was evaluated against a wide variety of herpesviruses and was found to be a highly selective inhibitor of replication of the gammaherpesviruses kaposi's sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv). hdvd had also a pronounced inhibitory activity against murine herpesvirus 68 (mhv-68) and herpes simplex virus 1 (hsv-1). in contrast, replication of herpesvir ...201323345517
synergistic activity of amenamevir (asp2151) with nucleoside analogs against herpes simplex virus types 1 and 2 and varicella-zoster virus.asp2151 (amenamevir) is a helicase-primase complex inhibitor with antiviral activity against herpes simplex virus hsv-1, hsv-2, and varicella-zoster virus (vzv). to assess combination therapy of asp2151 with existing antiherpes agents against hsv-1, hsv-2, and vzv, we conducted in vitro and in vivo studies of two-drug combinations. the combination activity effect of asp2151 with nucleoside analogs acyclovir (acv), penciclovir (pcv), or vidarabine (vdb) was tested via plaque-reduction assay and m ...201323261844
the challenge of developing a herpes simplex virus 2 vaccine.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. thera ...201223252387
[the genotyping and molecular evolution of varicella-zoster virus].varicella-zoster virus (vzv, human herpesvirus 3) is a member of the family herpesviridae, and is classified as alpha-subfamily along with hsv-1 and hsv-2. vzv is the causative agent of chicken pox (varicella) mostly in children, after which it establishes latency in the sensory ganglia with the potential to reactivate at a later time to cause shingles (zoster). increasing molecular epidemiological studies in recent years have been performed to monitor the mutations in vzv genome, discriminate v ...201223233938
anti-herpes virus activities of achyranthes aspera: an indian ethnomedicine, and its triterpene acid.the aim of this study was to evaluate the antiviral potential of methanolic extract (me) of achyranthes aspera, an indian folk medicine and one of its pure compound oleanolic acid (oa) against herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2). the me possessed weak anti-herpes virus activity (ec50 64.4μg/ml for hsv-1 and 72.8μg/ml for hsv-2). while oa exhibited potent antiherpesvirus activity against both hsv-1 (ec50 6.8μg/ml) and hsv-2 (ec50 7.8μg/ml). the time response study revealed that ...201323218996
herpesvirus entry mediator is a serotype specific determinant of pathogenesis in ocular herpes.infection with herpes simplex virus type 1 (hsv-1) and hsv-2 is initiated by viral glycoprotein d (gd) binding to a receptor on the host cell. two receptors, herpesvirus entry mediator (hvem) and nectin-1, mediate entry in murine models of hsv-1 and hsv-2. hvem is dispensable for hsv-2 infection of the vagina and brain, but is required for wt pathogenesis of hsv-1 infection of the cornea. by challenging wt and hvem ko mice with multiple strains of hsv-1 and hsv-2, we demonstrate that without hve ...201223184983
the mirnas of herpes simplex virus (hsv).herpes simplex virus (hsv) is a group of common human pathogens with two serotypes hsv-1 and hsv-2. the prevalence of hsv is worldwide. it primarily infects humans through epithelial cells, when it introduces a latent infection into the nervous system. during viral latency, only a region known as the latency-associated transcript (lat) is expressed. the discovery of hsv mirnas helps to draw a larger picture of the infection and pathogenesis of the virus. this review summarizes mirnas found in hs ...201223180288
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