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seroprevalence of herpes simplex virus infection in hiv coinfected individuals in eastern india with risk factor analysis.herpes simplex virus type 2 (hsv-2) is the cause of most genital herpes while hsv-1 is responsible for orolabial and facial lesions. in immunocompromised individuals, like hiv patients, impaired immunity leads to more frequent symptomatic and asymptomatic hsv infection. fifty-two blood samples from hiv patients with clinically diagnosed hsv infection were taken as cases, while 45 blood samples each from hiv-infected (hiv control) and noninfected patients without any herpetic lesion (non-hiv cont ...201526557849
herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection.herpes simplex virus (hsv) was originally implicated in the aetiology of cervical cancer, and although high-risk human papillomavirus (hpv) is now the accepted causative agent, the epidemiological link between hsv and hpv-associated cancers persists. the annexin a2 heterotetramer (a2t) has been shown to mediate infectious hpv type 16 (hpv16) uptake by human keratinocytes, and secretory leukocyte protease inhibitor (slpi), an endogenous a2t ligand, inhibits hpv16 uptake and infection. interesting ...201626555393
herpes simplex virus type 2 encephalitis as a cause of ischemic stroke: case report and systematic review of the literature.our objective is to describe a patient who developed an ischemic stroke as a complication of herpes simplex virus type 2 (hsv-2) encephalitis and to review the literature.201626542825
herpes simplex virus and varicella zoster virus: recent advances in therapy.the mainstay of antiviral therapy for the alpha-herpesviruses [herpes simplex virus (hsv)-1, hsv-2, and varicella zoster virus (vzv)] over the past 40 years has been the nucleoside analogues such as aciclovir. although conventional antiviral therapy has reduced mortality in severe disease, novel agents are needed to address the emergence of resistance and toxicity associated with current second-line therapy. treatment and prophylaxis of vzv and hsv reactivations remains a challenge.201526524331
global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012.herpes simplex virus type 1 (hsv-1) commonly causes orolabial ulcers, while hsv-2 commonly causes genital ulcers. however, hsv-1 is an increasing cause of genital infection. previously, the world health organization estimated the global burden of hsv-2 for 2003 and for 2012. the global burden of hsv-1 has not been estimated.201526510007
detection of virus in csf from the cases with meningoencephalitis by next-generation sequencing.we screened for viral dna in cerebrospinal fluid samples using next-generation sequencing (ngs) technology to diagnose cns viral infections. we collected csf samples from four cases with clinically suspected viral meningoencephalitis. dna extracted from the samples was analyzed with ngs, and the results were further validated using pcr. herpes simplex virus 1 (hsv-1) was detected in the csf of two patients, hsv-2 and human herpes virus type 3 (hhv-3, vzv) in the csf of two other patients separat ...201626506841
characterization of a herpes simplex virus 1 (hsv-1) chimera in which the us3 protein kinase gene is replaced with the hsv-2 us3 gene.us3 protein kinases encoded by herpes simplex virus 1 (hsv-1) and 2 (hsv-2) play important roles in viral replication and pathogenicity. to investigate type-specific differences between hsv-1 us3 and hsv-2 us3 in cells infected by viruses with all the same viral gene products except for their us3 kinases, we constructed and characterized a recombinant hsv-1 in which its us3 gene was replaced with the hsv-2 us3 gene. replacement of hsv-1 us3 with hsv-2 us3 had no apparent effect on viral growth i ...201526491159
functional characterization of glycoprotein h chimeras composed of conserved domains of the pseudorabies virus and herpes simplex virus 1 homologs.membrane fusion is indispensable for entry of enveloped viruses into host cells. the conserved core fusion machinery of the herpesviridae consists of glycoprotein b (gb) and the gh/gl complex. recently, crystal structures of gh/gl of herpes simplex virus 2 (hsv-2) and epstein-barr virus and of a core fragment of pseudorabies virus (prv) gh identified four structurally conserved gh domains. to investigate functional conservation, chimeric genes encoding combinations of individual domains of prv a ...201526491153
comparative evaluation of amplivue hsv 1+2 assay with elvis culture for detecting herpes simplex virus 1 (hsv-1) and hsv-2 in clinical specimens.the amplivue hsv 1+2 assay was compared to the elvis hsv id and d(3) typing culture system for the qualitative detection and differentiation of herpes simplex virus 1 (hsv-1) and hsv-2 dna in 1,351 cutaneous and mucocutaneous specimens. compared to elvis, amplivue had sensitivities of 95.7 and 97.6% for detecting hsv-1 and hsv-2, respectively. following arbitration of discordant results by an independent molecular method, the amplivue assay had a resolved sensitivity and specificity of 99.2 and ...201526468497
database on natural polymorphisms and resistance-related non-synonymous mutations in thymidine kinase and dna polymerase genes of herpes simplex virus types 1 and 2.the use of genotypic resistance testing of herpes simplex virus types 1 and 2 (hsv-1 and hsv-2) is increasing because the rapid availability of results significantly improves the treatment of severe infections, especially in immunocompromised patients. however, an essential precondition is a broad knowledge of natural polymorphisms and resistance-associated mutations in the thymidine kinase (tk) and dna polymerase (pol) genes, of which the dna polymerase (pol) enzyme is targeted by the highly ef ...201626433780
testing for herpes simplex virus in low-volume cerebrospinal fluid samples: comparison of three protocols to optimize detection.detection of herpes simplex virus 1 and 2 (hsv-1 and hsv-2) in cerebrospinal fluid (csf) is a medical emergency and requires rapid, sensitive testing. however, the volume of csf received for microbiological studies may be limited, especially from young children. in this study, we compared three testing protocols to our routine real-time pcr method to determine the most sensitive approach for detecting hsv-1 and hsv-2 in low-volume (≤100 μl) csf.201526400783
harmine blocks herpes simplex virus infection through downregulating cellular nf-κb and mapk pathways induced by oxidative stress.herpes simplex virus types 1 and 2 (hsv-1 and -2) are highly prevalent in many populations and therapeutic options are limited. both viruses can establish latency by maintaining viral genomes in neurons of sensory ganglia. primary or recurrent hsv infections may lead to deleterious outcomes: hsv-1 infection may result in corneal blindness and encephalitis and hsv-2 infection leads to herpes genitalis. while no effective vaccine is available, acyclovir is widely used for therapy, which targets an ...201526348003
is herpes simplex a systemic disease?orofacial herpes simplex virus infections are usually caused by herpes simplex virus 1 (hsv-1), and hsv-2 infections have been accepted as a sexually transmitted disease. hsv establishes a latent infection in the dorsal root ganglia of the host and remains there for the rest of life. hsv affects mainly skin and genitalia, although in immunocompromised patients it may cause local infection with vast skin involvement, chronic herpetic ulcers, or widespread mucous membrane damage, as well as system ...201526321402
carriage of herpes simplex virus and human papillomavirus in oral mucosa is rare in young women: a long-term prospective follow-up.following the primary oral infection, herpes simplex virus (hsv) establishes latency in the ganglia of sensory neurons. episodically induced by stress, hsv is able to cause recurrent infection at the primary infection site, accompanied by virus shedding. the oral shedding of hsv contributes to mother-child-transmission of hsv. human papillomavirus (hpv) is associated with oral malignancies, and its interaction with oral hsv should be studied further.201526305821
clinical evaluation of a helicase-dependant amplification (hda)-based commercial assay for the simultaneous detection of hsv-1 and hsv-2.in this study, we evaluate the performance of a commercial assay, the amplivue hsv 1+2 assay (quidel), which employs hda for the detection of both hsv-1 and hsv-2. the assay was tested on 307 clinical specimens (genital, oral, and dermal). when compared to shell vial virus culture and immunofluorescence typing of hsv, the positive percent agreement and negative percent agreement values were 98.2% and 90.9%, respectively. excellent assay performance was demonstrated.201526302856
seroprevalence of herpes simplex virus type 1 and type 2 and coinfection with hiv and syphilis: the first national seroprevalence survey in saudi arabia.herpes simplex virus (hsv) infection is one of the most common viral infections worldwide. genital herpes is associated with other sexually transmitted infections (stis) including hiv. data on prevalence of hsv infections and other stis in the kingdom of saudi arabia are limited.201526267880
additionally sulfated xylomannan sulfates from scinaia hatei and their antiviral activities.herpes simplex viruses (hsvs) display affinity for cell-surface heparan sulfate proteoglycans with biological relevance in virus entry. this study demonstrates the potential of chemically engineered sulfated xylomannans from scinaia hatei as antihsv drug candidate. particularly, a dimethylformamide -so3/pyridine based procedure has been employed for the generation of anionic polysaccharides. this one-step procedure has the power of providing a spectrum of xylomannans with varying molecular masse ...201526256190
seroprevalence of herpes simplex virus type 1 and 2 in taiwan and risk factor analysis, 2007.herpes simplex virus type 1 (hsv-1) and 2 (hsv-2) are common human pathogens and might cause severe illness. following primary infection, the viruses establish lifelong latent infection and are transmitted by close contact, both sexual and nonsexual. however, the information about the seroprevalence of hsv-1 and hsv-2 across all age groups is limited.201526252011
icacinlactone h and icacintrichantholide from the tuber of icacina trichantha.the 17-norpimarane diterpene is a small group of natural products. a new member, icacinlactone h (1), and a new rearranged 17-norpimarane with an unprecedented carbon skeleton, icacintrichantholide (2), were isolated from icacina trichantha. their structures including the absolute configuration were elucidated by spectroscopic analysis, single-crystal x-ray diffraction, and electronic circular dichroism analysis. a plausible biogenetic pathway for 1 and 2 is proposed. both 1 and 2 showed no sign ...201526183449
the telomerase inhibitor mst-312 interferes with multiple steps in the herpes simplex virus life cycle.the life cycle of herpes simplex virus (hsv) has the potential to be further manipulated to yield novel, more effective therapeutic treatments. recent research has demonstrated that hsv-1 can increase telomerase activity and that expression of the catalytic component of telomerase, telomerase reverse transcriptase (tert), alters sensitivity to hsv-dependent apoptosis. telomerase is a cellular enzyme that synthesizes nucleotide repeats at the ends of chromosomes (telomeres), which prevents shorte ...201526178994
efficacy of the herpes simplex virus 2 (hsv-2) glycoprotein d/as04 vaccine against genital hsv-2 and hsv-1 infection and disease in the cotton rat sigmodon hispidus model.subunit vaccines based on the herpes simplex virus 2 (hsv-2) glycoprotein d (gd-2) have been the major focus of hsv-2 vaccine development for the past 2 decades. based on the promising data generated in the guinea pig model, a formulation containing truncated gd-2, aluminum salt, and mpl (gd/as04) advanced to clinical trials. the results of these trials, however, were unexpected, as the vaccine protected against hsv-1 infection but not against hsv-2. to address this discrepancy, we developed a d ...201526178984
herpes simplex virus type 2 infection induces ad-like neurodegeneration markers in human neuroblastoma cells.herpes simplex virus (hsv) types 1 and 2 are neurotropic viruses that establish lifelong latent infections in neurons. mounting evidence suggests that hsv-1 infection is involved in the pathogenesis of alzheimer's disease (ad). the relationships between other herpesvirus infections and events associated with neurodegeneration have not, however, been extensively studied. the present work reports that hsv-2 infection leads to the strong accumulation of hyperphosphorylated tau and the amyloid-β pep ...201526163986
cellphone-based hand-held microplate reader for point-of-care testing of enzyme-linked immunosorbent assays.standard microplate based enzyme-linked immunosorbent assays (elisa) are widely utilized for various nanomedicine, molecular sensing, and disease screening applications, and this multiwell plate batched analysis dramatically reduces diagnosis costs per patient compared to nonbatched or nonstandard tests. however, their use in resource-limited and field-settings is inhibited by the necessity for relatively large and expensive readout instruments. to mitigate this problem, we created a hand-held a ...201526159546
antiherpes evaluation of soybean isoflavonoids.the antiviral effects of soybean isoflavonoids have been investigated recently, especially those of genistein. it has been reported that this isoflavone is able to inhibit herpes simplex virus (hsv) replication, which is associated with skin and epithelial mucosa infections. the treatment of these infections with antiherpes drugs has resulted in the emergence of resistant viral strains. based on this evidence, the aim of this study was to investigate the anti-hsv effects of soybean isoflavonoids ...201526156104
neonatal herpes simplex virus infection.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. diagnost ...201526154662
urinary micrornas of prostate cancer: virus-encoded hsv1-mirh18 and hsv2-mir-h9-5p could be valuable diagnostic markers.micrornas (mirnas) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (bph) and prostate cancer (pca). the aim of the study was to identify and validate urinary cell-free mirnas that can segregate patients with pca from those with bph.201526126436
patient-specific neutralizing antibody responses to herpes simplex virus are attributed to epitopes on gd, gb, or both and can be type specific.herpes simplex virus 1 (hsv-1) and hsv-2 infect many humans and establish a latent infection in sensory ganglia. although some infected people suffer periodic recurrences, others do not. infected people mount both cell-mediated and humoral responses, including the production of virus-neutralizing antibodies (abs) directed at viral entry glycoproteins. previously, we examined iggs from 10 hsv-seropositive individuals; all neutralized virus and were directed primarily against gd or gd+gb. here, we ...201526109729
laboratory diagnosis and epidemiology of herpes simplex 1 and 2 genital infections.herpes simplex virus types 1 and 2 are the main cause of genital ulcers worldwide. although herpes simplex virus type 2 is the major cause of genital lesions, herpes simplex virus type 1 accounts for half of new cases in developed countries. herpes simplex virus type 2 seroprevalence rises with sexual activity from adolescence through adulthood. slovenian data in a high-risk population shows 16% seroprevalence of hsv-2. hsv-1 and hsv-2 dna in genital swabs was detected in 19% and 20.7%, respecti ...201526086165
herpes simplex virus 1 reactivates from autonomic ciliary ganglia independently from sensory trigeminal ganglia to cause recurrent ocular disease.herpes simplex virus 1 (hsv-1) and hsv-2 establish latency in sensory and autonomic neurons after ocular or genital infection, but their recurrence patterns differ. hsv-1 reactivates from latency to cause recurrent orofacial disease, and while hsv-1 also causes genital lesions, hsv-2 recurs more efficiently in the genital region and rarely causes ocular disease. the mechanisms regulating these anatomical preferences are unclear. to determine whether differences in latent infection and reactivati ...201526041294
genome sequencing and analysis of geographically diverse clinical isolates of herpes simplex virus 2.herpes simplex virus 2 (hsv-2), the principal causative agent of recurrent genital herpes, is a highly prevalent viral infection worldwide. limited information is available on the amount of genomic dna variation between hsv-2 strains because only two genomes have been determined, the hg52 laboratory strain and the newly sequenced sd90e low-passage-number clinical isolate strain, each from a different geographical area. in this study, we report the nearly complete genome sequences of 34 hsv-2 low ...201526018166
global diversity within and between human herpesvirus 1 and 2 glycoproteins.human herpes simplex viruses 1 and 2 (hsv-1 and hsv-2) are large-genome dna viruses that establish a persistent infection in sensory neurons and commonly manifest with recurring oral or genital erosions that transmit virus. hsv encodes 12 predicted glycoproteins that serve various functions, including cellular attachment, entry, and egress. glycoprotein g is currently the target of an antibody test to differentiate hsv-1 from hsv-2; however, this test has shown reduced capacity to differentiate ...201526018161
partial and total c-6 oxidation of gelling carrageenans. modulation of the antiviral activity with the anionic character.the optimal conditions for the full c-6 oxidation of κ- and ι-carrageenans using (2,2,6,6-tetramethylpiperidinyl)oxy (tempo) in the presence of sodium hypochlorite and sodium bromide were assessed. the fully oxidized products were characterized by nmr spectroscopy. partially oxidized products were also obtained and analyzed by chemical and spectroscopical methods. the antiviral activity of carrageenans against herpes simplex virus hsv-1 and hsv-2 determined by plaque reduction assay, was not lar ...201526005156
application of mccoy cell line for propagation of herpes simplex virus type 1.herpes simplex virus types 1 (hsv-1) and 2 (hsv-2) are members of the herpesviridae family. about 40% to 80% of the world populations are infected with hsv and its prevalence is high in iran. the high prevalence of this virus in the community and the ability of the virus in causing fatal diseases among immunocompromised patients, have encouraged studies to be performed on hsv and suitable cell lines which supports the propagation of hsv. the aim of this study was to evaluate the suitability of m ...201525999628
obstetric outcomes of human herpes virus-2 infection among pregnant women in benin, nigeria.this study investigated the obstetric outcomes of herpes simplex virus (hsv-2) infection among pregnant women.201525966714
upstream binding factor inhibits herpes simplex virus replication.herpes simplex virus 1 (hsv-1) infection induces changes to the host cell nucleus including relocalization of the cellular protein upstream binding factor (ubf) from the nucleolus to viral replication compartments (vrcs). herein, we tested the hypothesis that ubf is recruited to vrcs to promote viral dna replication. surprisingly, infection of ubf-depleted hela cells with hsv-1 or hsv-2 produced higher viral titers compared to controls. reduced expression of ubf also led to a progressive increas ...201525965800
the immunomodulator, ammonium trichloro[1,2-ethanediolato-o,o']-tellurate, suppresses the propagation of herpes simplex virus 2 by reducing the infectivity of the virus progeny.persistent investigations for the identification of novel anti-herpetic drugs are being conducted worldwide, as current treatment options are sometimes insufficient. the immunomodulator, ammonium trichloro[1,2‑ethanediolato‑o,o']‑tellurate (as101), a non‑toxic tellurium (ⅳ) compound, has been shown to exhibit anti‑viral activity against a variety of viruses in cell cultures and in animal models. in the present study, the anti‑viral activity of as101 against herpes simplex virus (hsv)‑1 and 2 was ...201525936393
evasion of early antiviral responses by herpes simplex viruses.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, herpe ...201525918478
a spiroketal-enol ether derivative from tanacetum vulgare selectively inhibits hsv-1 and hsv-2 glycoprotein accumulation in vero cells.the inhibitory effects of tanacetum vulgare rhizome extracts on hsv-1 and hsv-2 in vitro replication were assessed. unlike extracts obtained from the aerial parts, adsorption inhibition and virucidal activities seemed not to be relevant for the observed antiviral action of tansy rhizome extracts. instead, the most significant effects were the inhibition of virus penetration and a novel mechanism consisting of the specific arrest of viral gene expression and consequently the decrease of viral pro ...201525882624
synergistic effects of acyclovir and 3, 19-isopropylideneandrographolide on herpes simplex virus wild types and drug-resistant strains.an andrographolide analogue, 3, 19-isopropylideneandrographolide (ipad), exerts an inhibitory effect on replication of wild-type herpes simplex virus serotype 1 (hsv-1). in this study, we examined the anti-viral activity of ipad on hsv wild types (hsv-1 strain kos and hsv-2 clinical isolate) and hsv-1 drug-resistant strains (drs). synergistic effects of ipad with acyclovir (acv) were also evaluated.201525879785
seroprevalence and seroincidence of herpes simplex virus (2006-2010), syphilis (2006-2010), and vaccine-preventable human papillomavirus subtypes (2000-2010) among us military personnel.sexually transmitted infections have historically been burdensome in military populations. we describe the seroprevalence and seroincidence of vaccine-preventable human papillomavirus (vp-hpv) subtypes in a sample of 200 servicemen, along with the seroprevalence and seroincidence of herpes simplex virus (hsv-1/2) and syphilis in a sample of 200 men and 200 women.201525868137
reactivation of herpes simplex type 1 in pneumococcal meningitis.acute bacterial meningitis (abm) and herpes simplex type 1 (hsv-1) encephalitis are two rare but serious infections affecting the central nervous system (cns). concurrent bacterial and viral cns infection has occasionally been reported.201525866347
genomic, phylogenetic, and recombinational characterization of herpes simplex virus 2 strains.herpes simplex virus 2 (hsv-2) is a major global pathogen, infecting 16% of people 15 to 49 years old worldwide and causing recurrent genital ulcers. little is known about viral factors contributing to virulence, and there are currently only two genomic sequences available. in this study, we determined nearly complete genomic sequences of six additional hsv-2 isolates, using illumina miseq. we report that hsv-2 has a genomic overall mean distance of 0.2355%, which is less than that of hsv-1. the ...201525855744
genital herpes: oral antiviral treatments.genital herpes is an infection with herpes simplex virus type 1 (hsv-1) or type 2 (hsv-2), and is among the most common sexually transmitted diseases.201525853497
immunogenicity, protective efficacy, and non-replicative status of the hsv-2 vaccine candidate hsv529 in mice and guinea pigs.hsv-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. a replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. however, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (hsv529) derived from dl5-29 have not been evaluated. humoral and cellular immune responses were measured in mice and guinea pigs immunized with hsv529. protecti ...201525837802
sero-prevalence of herpes simplex type 2 virus (hsv-2) and hiv infection in kampala, uganda.prevalence of herpes simplex type 2 virus (hsv-2) is high worldwide. previous studies in uganda were rural or in women. we estimated age and sex-specific sero-prevalence of hsv-2 in kampala, uganda.201425834483
necroptosis: the trojan horse in cell autonomous antiviral host defense.herpesviruses suppress cell death to assure sustained infection in their natural hosts. murine cytomegalovirus (mcmv) encodes suppressors of apoptosis as well as m45-encoded viral inhibitor of rip activation (vira) to block rip homotypic interaction motif (rhim)-signaling and recruitment of rip3 (also called ripk3), to prevent necroptosis. mcmv and human cytomegalovirus encode a viral inhibitor of caspase (casp)8 activation to block apoptosis, an activity that unleashes necroptosis. herpes simpl ...201525819165
the effect of menopause on the innate antiviral activity of cervicovaginal lavage.reproductive hormones are known to impact innate mucosal immune function of the lower genital tract. our objectives were to determine the effect of hormonal status on intrinsic antiviral (herpes simplex virus [hsv]-1, hsv-2, and human immunodeficiency virus [hiv]-1) activity of cervicovaginal lavage (cvl).201525818668
renal allograft re-use and herpetic re-infection.a middle-aged man received a kidney transplant from a deceased multi-organ donor. the recipient suffered cardiac arrest several days post-operatively and sustained hypoxic brain injury and was declared brain dead. following the family's consent, the allograft kidney was retrieved and re-transplanted into a man with end-stage renal failure secondary to reflux nephropathy. the liver was not transplanted due to suspicion of fatty changes based on macroscopic appearance. after transplantation of oth ...201525807853
in vitro evaluation of the antiviral properties of shilajit and investigation of its mechanisms of action.shilajit, a herbomineral substance exuded from rocks in steep mountainous regions, has been used for thousands of years by the indian ayurvedic and siddha systems of traditional medicine to relieve ailments and enhance quality of life. although a large number of therapeutic properties have been ascribed to shilajit, its therapeutic potential is still largely unexplored by modern research and many of its claimed bioactivities lack scientific validation. the present study was undertaken to investi ...201525792012
herpes simplex type 2 virus deleted in glycoprotein d protects against vaginal, skin and neural disease.subunit vaccines comprised of glycoprotein d (gd-2) failed to prevent hsv-2 highlighting need for novel strategies. to test the hypothesis that deletion of gd-2 unmasks protective antigens, we evaluated the efficacy and safety of an hsv-2 virus deleted in gd-2 and complemented allowing a single round of replication on cells expressing hsv-1 gd (δgd(-/+gd-1)). subcutaneous immunization of c57bl/6 or balb/c mice with δgd(-/+gd1) provided 100% protection against lethal intravaginal or skin challeng ...201525756612
novel rat models to study primary genital herpes simplex virus-2 infection.in this study we describe that six rat models (sd, wist, lew, bn, f344 and da) are susceptible to intravaginal herpes simplex virus-2 (hsv-2) infection after pre-treatment with progesterone. at a virus dose of 5 × 10(6) pfu of hsv-2, all rat models were infected presenting anti-hsv-2 antibodies, infectious virus in vaginal washes, and hsv-2 dna genome copies in lumbosacral dorsal root ganglia and the spinal cord. most of the lew, bn, f344, and da rats succumbed in systemic progressive symptoms a ...201525701211
neonatal herpes simplex virus infection: epidemiology and treatment.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 c ...201525677996
herpes simplex virus suppresses necroptosis in human cells.herpes simplex virus (hsv)-1 and hsv-2 are significant human pathogens causing recurrent disease. during infection, hsv modulates cell death pathways using the large subunit (r1) of ribonucleotide reductase (rr) to suppress apoptosis by binding to and blocking caspase-8. here, we demonstrate that hsv-1 and hsv-2 r1 proteins (icp6 and icp10, respectively) also prevent necroptosis in human cells by inhibiting the interaction between receptor-interacting protein kinase 1 (rip1) and rip3, a key step ...201525674983
houttuynia cordata targets the beginning stage of herpes simplex virus infection.herpes simplex virus (hsv), a common latent virus in humans, causes certain severe diseases. extensive use of acyclovir (acv) results in the development of drug-resistant hsv strains, hence, there is an urgent need to develop new drugs to treat hsv infection. houttuynia cordata (h. cordata), a natural herbal medicine, has been reported to exhibit anti-hsv effects which is partly nf-κb-dependent. however, the molecular mechanisms by which h. cordata inhibits hsv infection are not elucidated thoro ...201525643242
herpes simplex virus enhances chemokine function through modulation of receptor trafficking and oligomerization.glycoprotein g (gg) from herpes simplex virus 1 and 2 (hsv-1 and hsv-2, important human neurotropic pathogens) is the first viral chemokine-binding protein found to potentiate chemokine function. here we show that gg attaches to cell surface glycosaminoglycans and induces lipid raft clustering, increasing the incorporation of cxcr4 receptors into these microdomains. gg induces conformational rearrangements in cxcr4 homodimers and changes their intracellular partners, leading to sustained, functi ...201525625471
secreted herpes simplex virus-2 glycoprotein g modifies ngf-trka signaling to attract free nerve endings to the site of infection.herpes simplex virus type 1 (hsv-1) and hsv-2 are highly prevalent viruses that cause a variety of diseases, from cold sores to encephalitis. both viruses establish latency in peripheral neurons but the molecular mechanisms facilitating the infection of neurons are not fully understood. using surface plasmon resonance and crosslinking assays, we show that glycoprotein g (gg) from hsv-2, known to modulate immune mediators (chemokines), also interacts with neurotrophic factors, with high affinity. ...201525611061
severe acute pharyngotonsillitis due to herpes simplex virus type 2 in a young woman.whereas herpes simplex virus type 1 (hsv-1) is a recognized cause of acute oropharyngeal infection in young adults, hsv-2 infections are mostly associated with genital symptoms. we report a case of acute and prolonged febrile ulcerative pharyngotonsillitis with inflammatory syndrome which persisted despite antibiotic therapy for 8 days and required hospitalization in an 18-year old immune competent and sexually active female patient. hsv-2 was evidenced in tonsillar samples and blood by real tim ...201525600608
first identification of the herpes simplex virus by skin-dedicated ex vivo fluorescence confocal microscopy during herpetic skin infections.skin-dedicated ex vivo fluorescence confocal microscopy (fcm) has so far been used to identify cutaneous tumours on freshly excised samples using acridine orange as fluorochrome.201525545312
functional comparison of herpes simplex virus 1 (hsv-1) and hsv-2 icp27 homologs reveals a role for icp27 in virion release.numerous studies have focused on the regulatory functions of icp27, an immediate-early (ie) protein of herpes simplex virus 1 (hsv-1). however, its homolog in hsv-2, termed icp27t2, has been little studied. here, we used two different approaches to functionally compare icp27t2 and icp27. in transfection-based assays, icp27t2 closely resembled icp27 in its capacity to enhance hsv-1 late gene expression, suppress the splicing of a viral intron, and complement the growth of an hsv-1 icp27 null muta ...201525540385
production of a fragment of glycoprotein g of herpes simplex virus type 2 and evaluation of its diagnostic potential.herpes simplex virus type 2 (hsv-2) is the most common cause of genital herpes. glycoprotein g (gg) is a prototype antigen for type-specific serodiagnosis distinguishing between hsv type 1 (hsv-1) and hsv-2 infections. as immunological diagnosis kits for accurate differentiation between hsv-1 and hsv-2 antibodies can be expensive, there is a need to develop a convenient, sensitive, specific and cost-effective serodiagnostic kit.201525532518
congenital disseminated hsv-1 infection in preterm twins after primary gingivostomatitis of the mother: case report and review of the literature.transplacental transmission of hsv infection is rare, typically associated with herpes simplex virus 2 (hsv-2) and often reported in term infants, whereas only a few cases of preterm infants with herpes simplex virus 1 (hsv-1) infection are found in the literature. we report the case of a transplacental hsv-1 infection in preterm twins born at 27 weeks gestation. at 23 weeks gestation the mother had experienced primary gingivostomatitis and "flu-like" symptoms, which healed without specific trea ...201425518832
evaluation of 2 multiplex real-time pcr assays for the detection of hsv-1/2 and varicella zoster virus directly from clinical samples.we compared the performance of 2 multiplex assays (focus simplexa and quidel lyra) to individual real-time pcr for the detection of herpes simplex virus-1 (hsv-1), hsv-2, and varicella zoster virus (vzv) from clinical specimens. results were compared to a consensus standard, defined as the result obtained by at least 2 of the 3 molecular methods. the sensitivity of the quidel assay ranged from 92.0% for hsv-1 to 97.7% for hsv-2, while the specificity for all targets was 100%. the focus assay dem ...201525511233
comparison of the simplexa hsv1 & 2 direct kit and laboratory-developed real-time pcr assays for herpes simplex virus detection.rapid detection and differentiation of herpes simplex viruses (hsv) is important for patient management and treatment, especially in hsv meningoencephalitis.201525464965
herpes simplex virus infection during pregnancy.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 unc ...201425454993
fungal metabolite myriocin promotes human herpes simplex virus-2 infection.myriocin is a fungal metabolite with antiviral activity, including influenza, hepatitis b, and hepatitis c viruses. we investigated whether myriocin has activity against human hsv-2, one of the most prevalent pathogens of sexually transmitted disease.201525447452
the challenges and opportunities for the development of a t-cell epitope-based herpes simplex vaccine.herpes simplex virus type 1 and type 2 (hsv-1 & hsv-2) infections have been prevalent since the ancient greek times. to this day, they still affect a staggering number of over a billion individuals worldwide. hsv-1 infections are predominant than hsv-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. hsv-2 infections cause painful genital herpes, encephalitis, and death in newborns. while prophylactic and therapeutic hsv vaccines remain urgently needed ...201425446827
a case report of herpetic whitlow with positive kanavel's cardinal signs: a diagnostic and treatment difficulty.herpetic whitlow is an acute viral infection of the hand caused by either herpes simplex virus (hsv) 1 or 2. its characteristic findings are significant pain and erythema with overlying nonpurulent vesicles. the differential diagnosis includes flexor tenosynovitis. we present a case of recurrent infection of the middle finger in an immunocompetent 19-year-old girl. multiple painful pustules with tracking cellulitis were partially treated by oral antibiotics. a recurrence with positive kanavel's ...201425436164
[infections caused by human alpha herpes viruses].varicella-zoster virus (vzv), herpes simplex virus one (hsv-1) and herpes simplex virus two (hsv-2) represent three out of the eight known human herpesviruses and belong to the subfamily of α-herpesviruses. these viruses are present worldwide and humans are their sole host and reservoir. after the primary infection, these viruses persist in the body throughout life. the period of latency may be interrupted by reactivation of infection due to various factors. each virus can induce a wide spectrum ...201425412485
human semen contains exosomes with potent anti-hiv-1 activity.exosomes are membranous nanovesicles secreted into the extracellular milieu by diverse cell types. exosomes facilitate intercellular communication, modulate cellular pheno/genotype, and regulate microbial pathogenesis. although human semen contains exosomes, their role in regulating infection with viruses that are sexually transmitted remains unknown. in this study, we used semen exosomes purified from healthy human donors to evaluate the role of exosomes on the infectivity of different strains ...201425407601
hsv1 and 2 detection in the csf of multiple sclerosis patients by real-time pcr.the pathogenic role of herpes simplex virus (hsv) 1 and 2 in multiple sclerosis (ms) still remains obscure. the aim of our study was the assessment of hsv1 and 2 dna prevalence in the cerebrospinal fluid (csf) of ms patients compared to patients with other neurological disorders (ond).201425398824
animal models of herpes simplex virus immunity and pathogenesis.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 hum ...201525388226
development of a time-resolved fluorescence immunoassay for herpes simplex virus type 1 and type 2 igg antibodies.enzyme-linked immunosorbent assays (elisa) specific for anti-hsv glycoprotein g (gg) are most commonly used in the clinical diagnosis of hsv infection. but most of them are qualitative and with narrow detection ranges. a novel time-resolved fluoroimmunoassay (trfia) methodology was developed for the quantitative determination of hsv igg in human serum. the assay was based on an indirect immunoassay format, and performed in 96-well microtiter plates. hsv-1 and hsv-2 were used as the coating antig ...201525377426
antiherpetic mechanism of a sulfated derivative of agaricus brasiliensis fruiting bodies polysaccharide.to study the anti-herpes simplex virus (hsv) activity of a (1→6)-(1→3)-β-d-glucan isolated from agaricus brasiliensis fruiting bodies (fr) as well as its chemically sulfated derivative (fr-s).201425359160
simultaneous detection of herpes simplex virus 1 and 2 in the cerebrospinal fluid of a patient with seizures and encephalitis.we report a case of a 62-year-old female with seizures and encephalitis. molecular testing of the patient's cerebrospinal fluid was positive for both herpes simplex virus 1 and 2 (hsv-1 and hsv-2). to our knowledge, this is the first report of simultaneous detection of hsv-1 and hsv-2 in cerebrospinal fluid.201525355765
a single intramuscular vaccination of mice with the hsv-1 vc2 virus with mutations in the glycoprotein k and the membrane protein ul20 confers full protection against lethal intravaginal challenge with virulent hsv-1 and hsv-2 strains.herpes simplex virus type-1 (hsv-1) and type-2 (hsv-2) establish life-long infections and cause significant orofacial and genital infections in humans. hsv-1 is the leading cause of infectious blindness in the western world. currently, there are no available vaccines to protect against herpes simplex infections. recently, we showed that a single intramuscular immunization with an hsv-1(f) mutant virus lacking expression of the viral glycoprotein k (gk), which prevents the virus from entering int ...201425350288
entry mechanisms of herpes simplex virus 1 into murine epidermis: involvement of nectin-1 and herpesvirus entry mediator as cellular receptors.skin keratinocytes represent a primary entry site for herpes simplex virus 1 (hsv-1) in vivo. the cellular proteins nectin-1 and herpesvirus entry mediator (hvem) act as efficient receptors for both serotypes of hsv and are sufficient for disease development mediated by hsv-2 in mice. how hsv-1 enters skin and whether both nectin-1 and hvem are involved are not known. we addressed the impact of nectin-1 during entry of hsv-1 into murine epidermis and investigated the putative contribution of hve ...201525320325
[immune diagnostics of disorders in the ifn-alpha/nk-cell system in patients with frequently recurrent herpes simplex].study of features of nk-cell response to the effect of recombinant ifn-alpha in complex with evaluation of the ability to synthesize inherent ifn-alpha in patients with frequently recurrent herpes simplex (frhs).201525286509
development and optimization of a real-time pcr assay for detection of herpes simplex and varicella-zoster viruses in skin and mucosal lesions by use of the bd max open system.we transitioned laboratory-developed pcr assays for herpes simplex virus 1 (hsv-1), hsv-2, and varicella-zoster virus (vzv) to the bd max system by using bd max open system reagents. after optimization, the agreement with the reference pcr assay was 100% (123/123) for hsv-1, 96.7% (119/123) for hsv-2, and 100% (60/60) for vzv using retrospective clinical samples.201425275002
rapid and direct detection of herpes simplex virus in cerebrospinal fluid by use of a commercial real-time pcr assay.central nervous system infection due to herpes simplex virus (hsv) is a medical emergency and requires rapid diagnosis and initiation of therapy. in this study, we compared a routine real-time pcr assay for hsv types 1 (hsv-1) and 2 (hsv-2) to a recently fda-approved direct pcr assay (simplexa hsv-1/2 direct; focus diagnostics, cypress, ca) using cerebrospinal fluid samples (n = 100). the simplexa hsv-1/2 assays demonstrated a combined sensitivity and specificity of 96.2% (50/52) and 97.9% (47/4 ...201425274992
the role of antiviral therapy in immunocompromised patients with herpes simplex virus meningitis.herpes simplex virus types 1 and 2 (hsv-1 and hsv-2) are important causes of acute neurologic illness. although the role of acyclovir in treating hsv encephalitis is clear, the role of antiviral therapy in hsv meningitis remains controversial.201525273082
inhibitors of nucleotidyltransferase superfamily enzymes suppress herpes simplex virus replication.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 co ...201425267681
mother-to-child transmission of herpes simplex virus.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 re ...201425232472
crystal structure of herpes simplex virus 2 gd bound to nectin-1 reveals a conserved mode of receptor recognition.herpes simplex virus 1 (hsv-1) and hsv-2 are among the most prevalent human pathogens. both viruses can recognize, via the surface envelope glycoprotein d (gd), human nectin-1 as a functional receptor. previous studies have successfully elucidated the molecular basis of the binding between hsv-1 gd and nectin-1 by cocrystallography. despite a high sequence identity between hsv-1 and hsv-2 gds, the atomic intermolecule details for the hsv-2-gd/nectin-1 interaction remain elusive. here, we report ...201425231300
herpes simplex virus serotype and entry receptor availability alter cns disease in a mouse model of neonatal hsv.outcomes of neonates with herpes simplex virus (hsv) encephalitis are worse after infection with hsv-2 when compared with hsv-1. the proteins herpes virus entry mediator (hvem) and nectin-1 mediate hsv entry into susceptible cells. prior studies have shown receptor-dependent differences in pathogenesis that depend on route of inoculation and host developmental age.201425198371
prophylactic and therapeutic modulation of innate and adaptive immunity against mucosal infection of herpes simplex virus.herpes simplex virus types 1 and 2 (hsv-1 and hsv-2) are the most common cause of genital ulceration in humans worldwide. typically, hsv-1 and 2 infections via mucosal route result in a lifelong latent infection after peripheral replication in mucosal tissues, thereby providing potential transmission to neighbor hosts in response to reactivation. to break the transmission cycle, immunoprophylactics and therapeutic strategies must be focused on prevention of infection or reduction of infectivity ...201425177251
statistical analysis of amenamevir (asp2151) between pharmacokinetics and clinical efficacies with non-linear effect model for the treatment of genital herpes.amenamevir is the international non-proprietary name for asp2151 synthesized by astellas pharma, inc. it is a structurally novel class of helicase-primase inhibitor and demonstrated more potency in vitro anti-viral activity with low cytotoxicity against varicella-zoster virus (vzv), herpes simplex virus type 1 (hsv-1), and herpes simplex virus type 2 (hsv-2) than acyclovir (acv). phase ii randomized trial assessed the safety and efficacy of asp2151 for episodic therapy of recurrent genital herpe ...201427129009
wolf's post-herpetic isotopic response: infections, tumors, and immune disorders arising on the site of healed herpetic infection.herpes simplex viruses (hsv-1/hsv-2) and varicella-zoster virus (vzv) have several characteristics in common. both are epidermoneurotropic, cause skin eruptions accompanied by sensory symptoms (itch, pain), damage peripheral sensory nerve fibers and cutaneous nerve endings, and interfere with neuromediator release, which can alter local mechanisms of immune control. for this reason, herpes-infected areas may become a preferential location for the subsequent onset of immunity-related skin disorde ...201425160097
genital herpes.genital herpes is a relatively common infection caused by herpes simplex virus (hsv) type one or two (hsv-1, hsv-2) respectively. it is acquired most commonly via sexual activity. more recently there has been an increase in infections due to hsv-1. most new cases of genital hsv are not diagnosed due to hsv infections having short-lived signs and symptoms, or in many instances are asymptomatic. hence many people infected with hsv are unaware that they have it. the risk of transmission to a partne ...201425153069
herpes simplex virus meningitis in children in south east of caspian sea, iran.herpes simplex virus (hsv) is a member of herpesviridae and a leading cause of human viral diseases. meningitis occurs as a complication of hsv-1 or hsv-2 primary infection.201425147651
dissection of the antibody response against herpes simplex virus glycoproteins in naturally infected humans.relatively little is known about the extent of the polyclonal antibody (pab) repertoire elicited by herpes simplex virus (hsv) glycoproteins during natural infection and how these antibodies affect virus neutralization. here, we examined iggs from 10 hsv-seropositive individuals originally classified as high or low virus shedders. all pabs neutralized virus to various extents. we determined which hsv entry glycoproteins these pabs were directed against: glycoproteins gb, gd, and gc were recogniz ...201425142599
improving immunogenicity and efficacy of vaccines for genital herpes containing herpes simplex virus glycoprotein d.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 ...201425138572
herpes simplex virus types 1 and 2 modulate autophagy in sirc corneal cells.autophagy and apoptosis function as important early cellular defense mechanisms in infections and other diseases. the outcome of an infection is determined by a complex interplay between the pathogenic microorganism and these intracellular pathways. to better understand the cytopathogenicity of herpes simplex virus types 1 and 2 (hsv-1 and - 2), we studied the effect of these viruses on the autophagic and apoptotic processes in the sirc corneal cell line. infection with the kos strain of hsv-1 a ...201425116622
ellagitannins as synergists of acv on the replication of acv-resistant strains of hsv 1 and 2.the plant-derived polyphenolic compounds castalagin, vescalagin and grandinin (c-glucosidic ellagitannins containing nonahydroxyterphenoyl) manifested a strong inhibitory effect on the replication of acyclovir-resistant strains of herpes simplex viruses (hsv) type 1 and 2 in mdbk cells in focus forming units (i.e., microscopically registered microplaques) reduction assay and in two variants of cytopathic effect inhibition test. the effect on the acyclovir (acv)-resistant herpes simplex virus typ ...201425111906
cerebellar dysfunction in a patient with hiv.a 50-year-old aids patient with a cd4 t-cell count of 114/mm(3) was admitted with cerebellar symptoms of left cn xi weakness, wide-based gait with left-sided dysmetria, abnormal heel-knee-shin test, and dysdiadochokinesia. mri showed region of hyperintensity in the left inferior cerebellar hemisphere involving the cortex and underlying white matter. serological tests for hsv1, hsv2, and syphilis were negative. her csf contained high protein content and a wbc of 71/mm(3), predominantly lymphocyte ...201425093131
oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients.genital herpes is caused by herpes simplex virus 1 (hsv-1) or 2 (hsv-2). some infected people experience outbreaks of genital herpes, typically, characterized by vesicular and erosive localized painful genital lesions.201425086573
acute herpetic gingivostomatitis associated with herpes simplex virus 2: report of a case.herpetic gingivostomatitis represents the most commonly observed clinical manifestation of primary herpes simplex virus (hsv) infection. hsv-1 has been associated with oro-labial disease, with most infections occurring during childhood, and hsv-2 with genital disease. however, it is possible for hsv-2 to cause oro-labial herpes and hsv-1 to cause genital herpes. an unusual case of acute herpetic gingivostomatitis (ahgs) that presented as extremely painful multiple ulcerations of the gingiva and ...201425083042
clinical validation of the lyra direct hsv 1+2/vzv assay for simultaneous detection and differentiation of three herpesviruses in cutaneous and mucocutaneous lesions.we evaluated the lyra direct hsv 1+2/vzv multiplex real-time pcr assay for the detection and differentiation of herpes simplex virus 1 (hsv-1), hsv-2, and varicella-zoster virus (vzv) on 695 consecutive cutaneous and mucocutaneous lesion specimens. the intra-assay and interassay coefficient of variation values for the lyra assay were 0.29 to 1.30% and 2.33 to 2.61%, respectively. the sensitivities, specificities, and positive and negative predictive values were 93.4 to 95.0%, 96.1 to 96.8%, 78.0 ...201425078915
comparison of clinical manifestations, outcomes and cerebrospinal fluid findings between herpes simplex type 1 and type 2 central nervous system infections in adults.in previous reports on the viral causes of central nervous system (cns) infections, it has been generally recognized that hsv-1 is a major cause of encephalitis, while hsv-2 is the predominant cause of aseptic meningitis in adults. to examine this matter, the clinical characteristics in the two types of hsv cns infections were investigated. in a retrospective cohort study which included all adult patients (≥16 years) between january 1999 and december 2013 in a 2,700-bed tertiary care hospital, a ...201425042344
an attenuated herpes simplex virus type 1 (hsv1) encoding the hiv-1 tat protein protects mice from a deadly mucosal hsv1 challenge.herpes simplex virus types 1 and 2 (hsv1 and hsv2) are common infectious agents in both industrialized and developing countries. they cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. current treatment for hsv relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. therefore ...201425033084
up to four distinct polypeptides are produced from the γ34.5 open reading frame of herpes simplex virus 2.the herpes simplex virus 1 (hsv-1) icp34.5 protein strongly influences neurovirulence and regulates several cellular antiviral responses. despite the clinical importance of hsv-2, relatively little is known about its icp34.5 ortholog. we found that hsv-2 produces up to four distinct forms of icp34.5 in infected cells: a full-length protein, one shorter form sharing the n terminus, and two shorter forms sharing the c terminus. these forms appeared with similar kinetics and accumulated in cells ov ...201425031346
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