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prevalence of human papillomavirus infection among prostitutes in calcutta.we investigated the presence of human papilloma virus (hpv) 16/18 and herpes simplex virus-1,-2 (hsv-1,-2) infections in buccal mucosal cells of prostitutes of calcutta, india, by in situ dna hybridization and immunocytochemical technique. in some of them, we also examined the prevalence of viral infections in uterine cervical cells. the women were also tested for venereal disease research laboratory antigen (vdrl) positivity. oral infections with hsv-1, -2 and hpv 16/18 were detected in 24.6%, ...200111394709
antiviral activity of an extract derived from roots of eleutherococcus senticosus.a liquid extract from eleutherococcus senticosus roots inhibited the productive replication of human rhinovirus (hrv), respiratory syncytial virus (rsv) and influenza a virus in cell cultures infected with these viruses, all of which belong to the rna type viruses. analysis of virus production after treatment of the infected cells using plaque-reduction assays showed a strong antiviral activity of the eleutherococcus extract. in contrast, no effect was detected using the same protocol for cells ...200111397509
utilization of herpes simplex pcr assays for cerebrospinal fluid in a pediatric health care setting.an assessment was made of the utilization and impact of a diagnostic polymerase chain reaction (pcr) assay for the diagnosis of herpes simplex viruses (hsv) 1 and 2 in cerebrospinal fluid of children who attended a canadian pediatric referral centre. one hundred and three assays were performed on specimens from 103 patients during the period august 1997 to september 1998. patient ages ranged from newborn to 16 years. indications for hsv pcr included seizures with or without fever (56.3%), asepti ...200111400728
effect of famciclovir on herpes simplex virus type 1 corneal disease and establishment of latency in rabbits.famciclovir (fcv) is efficacious in the treatment of acute herpes zoster and recurrent genital infections but has not been used to treat ocular herpes simplex virus (hsv) infections. we evaluated the efficacy of orally administered fcv in treating hsv-1 epithelial keratitis and determined its effects on the establishment of latency and subsequent reactivation. rabbits were inoculated with hsv-1 strain 17 syn+ and treated twice daily with increasing concentrations of fcv (60 to 500 mg/kg of body ...200111408221
value of the dorsal cutaneous guinea pig model in selecting topical antiviral formulations for the treatment of recurrent herpes simplex type 1 disease.recurrent herpes simplex labialis represents a disease still difficult to treat, despite the availability of many established antiviral drugs used in clinical research since 30 years ago. although differences between the human disease and that obtained in experimental animal suggest caution in predicting an effective clinical response from the experimental results, some of the animal models seem to be useful in optimising the topical formulation of single antiviral drugs. in the present work the ...200111413746
commentary: developing preventive strategies in europe. 200111416088
complementary intrastrand base pairing during initiation of herpes simplex virus type 1 dna replication.the herpes simplex virus type 1 origin of dna replication, oris, contains three copies of the recognition sequence for the viral initiator protein, origin binding protein (obp), arranged in two palindromes. the central box i forms a short palindrome with box iii and a long palindrome with box ii. single-stranded oris adopts a conformation, oris*, that is tightly bound by obp. here we demonstrate that obp binds to a box iii-box i hairpin with a 3' single-stranded tail in oris*. mutations designed ...200111416203
regulation of herpes simplex virus gene expression.expression of the more than 80 individual genes of herpes simplex virus 1 (hsv-1) takes place in a tightly regulated sequential manner that was first described over 20 years ago. investigations since that time have focused on understanding the mechanisms that regulate this orderly and efficient expression of viral genes. this review examines recent findings that have shed light on how this process is regulated during productive infection of the cell. although the story is still not complete, sev ...200111418233
in vitro effect of oral antiseptics on human immunodeficiency virus-1 and herpes simplex virus type 1.the antiviral effectiveness of widely used commercial mouthrinses has not been well studied. a project was undertaken to evaluate and compare the in vitro antiviral effectiveness of essential oil-containing mouthrinses (la & tla) and chlorhexidine mouthrinses (px & chx) on 2 different enveloped viruses, human immunodeficiency virus (hiv-1) and herpes simplex virus (hsv-1) mcintyre strain.200111422581
obstructive hydrocephalus following herpes simplex virus type 1 encephalitis treated by repeated third ventriculostomy.a rare case of obstructive hydrocephalus due to aqueductal obstruction following neonatal herpes simplex virus type 1 encephalitis is presented. the child was treated by third ventriculostomy and vesicles were seen on the floor of the third ventricle. the stoma closed on two occasions and required repeat third ventriculostomy, which was successful in maintaining the child shunt-free.200111423775
5-(trifluoromethyl)-beta-l-2'-deoxyuridine, the l-enantiomer of trifluorothymidine: stereospecific synthesis and antiherpetic evaluations.as a part of our ongoing work on beta-l-nucleoside analogues as potential antiviral drugs, we have synthesized 5-(trifluoromethyl)-beta-l-2'-deoxyuridine (l-tft), the hitherto unknown l-enantiomer of trifluorothymidine (cf(3)durd, tft). we have also studied the effect of l-tft on human and herpes simplex virus (hsv) type 1 and 2 thymidine kinases, and human thymidine phosphorylase, as well as its anti-hsv-1 and anti-hsv-2 activities in cell cultures. l-tft has been found: (i) to inhibit hsv-1 tk ...200111425574
in vitro antiviral activity of the anthraquinone chrysophanic acid against poliovirus.chrysophanic acid (1,8-dihydroxy-3-methylanthraquinone), isolated from the australian aboriginal medicinal plant dianella longifolia, has been found to inhibit the replication of poliovirus types 2 and 3 (picornaviridae) in vitro. the compound inhibited poliovirus-induced cytopathic effects in bgm (buffalo green monkey) kidney cells at a 50% effective concentration of 0.21 and 0.02 microgram/ml for poliovirus types 2 and 3, respectively. the compound inhibited an early stage in the viral replica ...200111428243
positron emission tomography imaging for herpes virus infection: implications for oncolytic viral treatments of cancer.molecular therapy using viruses would benefit greatly from a non-invasive modality for assessing dissemination of viruses. here we investigated whether positron emission tomography (pet) scanning using [(124)i]-5-iodo-2'-fluoro-1-beta-d-arabinofuranosyl-uracil (fiau) could image cells infected with herpes simplex viruses (hsv). using replication-competent hsv-1 oncolytic viruses with thymidine kinase (tk) under control of different promoters, we demonstrate that viral infection, proliferation an ...200111433353
in vitro and in vivo activity of 1-o-hexadecylpropanediol-3-phospho-ganciclovir and 1-o-hexadecylpropanediol-3-phospho-penciclovir in cytomegalovirus and herpes simplex virus infections.human cytomegalovirus (hcmv) and herpes simplex virus (hsv) can cause a wide variety of clinical manifestations in man. ganciclovir (gcv) is effective against hcmv infection when administered by the intravenous route and may be used orally in large doses for prophylaxis of hcmv infections in organ transplantation patients and in aids patients. in previous studies with acyclovir (acv), we found that covalent attachment of an alkyl glycerol phosphate moiety greatly increased oral bioavailability a ...200111437323
enhanced antitumor efficacy of a herpes simplex virus mutant isolated by genetic selection in cancer cells.replication-competent, attenuated herpes simplex virus-1 (hsv-1) derivatives that contain engineered mutations into the viral gamma 34.5 virulence gene have been used as oncolytic agents. however, as attenuated mutants often grow poorly, they may not completely destroy some tumors and surviving cancer cells simply regrow. thus, although hsv-1 gamma 34.5 mutants can reduce the growth of human tumor xenografts in mice and have passed phase i safety studies, their efficacy is limited because they r ...200111438715
effective treatment of head and neck squamous cell carcinoma by an oncolytic herpes simplex virus.the prognosis of patients with advanced or recurrent head and neck squamous cell carcinoma remains poor despite refinements in multimodality therapies. this study evaluates the efficacy of a replication-competent, attenuated, oncolytic herpes simplex virus, nv1020, as a novel agent in the treatment of human head and neck squamous cell carcinoma (hnscc).200111442249
the infected cell protein 0 of herpes simplex virus 1 dynamically interacts with proteasomes, binds and activates the cdc34 e2 ubiquitin-conjugating enzyme, and possesses in vitro e3 ubiquitin ligase activity.the infected cell protein 0 (icp0) of herpes simplex virus 1, a promiscuous transactivator shown to enhance the expression of genes introduced into cells by infection or transfection, interacts with numerous cellular proteins and has been linked to the disruption of nd10 and degradation of several proteins. icp0 contains a ring finger domain characteristic of a class of e3 ubiquitin ligases. we report that: (i) in infected cells, icp0 interacts dynamically with proteasomes and is bound to protea ...200111447293
evidence for antigen-specific immune deviation in patients with acute retinal necrosis.because experimental acute retinal necrosis (arn) induced by herpes simplex virus in mice develops only if mice fail to acquire virus-specific delayed hypersensitivity (dh), although they produce antiviral antibodies (ie, anterior chamber-associated immune deviation), we sought to determine whether a similar inverse correlation exists for patients with varicella-zoster virus (vzv)-induced arn.200111448326
the downstream activation sequence of the strict late herpes simplex virus type 1 u(l)38 promoter interacts with htaf(ii)70, a component of tfiid.a class of strict late herpes simplex virus type 1 (hsv-1) promoters contains a conserved sequence element (termed the downstream activation sequence, das) located downstream of the transcription start site. these das-containing promoters also require both a tata box and an initiator element for maximal levels of transcription. in this communication, we demonstrate that the downstream promoter element (dpe) found on a class of drosophila tata-less promoters and known to bind the homologue of hum ...200111450948
picture perfect. 200111473279
oncogenes in ras signalling pathway dictate host-cell permissiveness to herpes simplex virus 1.the importance of herpes simplex viruses (hsv) as human pathogens and the emerging prospect of using mutant derivatives of hsv-1 as potential anti-cancer therapeutics have necessitated a thorough investigation into the molecular basis of host-cell permissiveness to hsv. here we show that nih-3t3 cells transformed with the oncogenes v-erbb, activated sos or activated ras become significantly more permissive to hsv-1. inhibitors of the ras signalling pathway, such as farnesyl transferase inhibitor ...200111483960
type i interferons and herpes simplex virus infection: a naked dna approach as a therapeutic option?herpes simplex virus (hsv) types 1 and 2 are highly successful human pathogens that can elicit blinding herpetic keratoconjunctivitis, fatal sporadic encephalitis, aseptic meningitis, and increase the risk of acquiring additional sexually transmitted diseases. type i interferons (ifn) play a significant role in controlling hsv pathogenesis by antagonizing viral replication and spread. taking advantage of the susceptibility of hsv to ifns, a novel approach of employing plasmid dna cassettes expre ...200111485206
[selective inhibition of hsv-1 dna and protein synthesis by antiviral antibiotic 17997].to study the effects of 17997 on the hsv-1 dna and protein synthesis.200011498689
herpetic gingivostomatitis in otherwise healthy adolescents and young adults.the purpose of this study was to review and analyze the records of herpes simplex infections from a specialist oral medicine clinic in iceland, to investigate the clinical impression that the age of patients experiencing initial infection with this virus was higher than expected and that the character of the clinical picture of the disease had changed. records of patients with herpes infections attending the oral medicine clinic covering a 3-year period were examined and the clinical and virolog ...200111501877
[the efficacy of antiviral antibiotic 17997 on treatment of hsv-1 infected guinea pig skin infection].to study the treatment efficacy of antiviral antibiotic 17997 against hsvl infected guinea pig skin infection.200011503040
intratumoral spread and increased efficacy of a p53-vp22 fusion protein expressed by a recombinant adenovirus.in vitro experiments have demonstrated intercellular trafficking of the vp22 tegument protein of herpes simplex virus type 1 from infected cells to neighboring cells, which internalize vp22 and transport it to the nucleus. vp22 also can mediate intercellular transport of fusion proteins, providing a strategy for increasing the distribution of therapeutic proteins in gene therapy. intercellular trafficking of the p53 tumor suppressor protein was demonstrated in vitro using a plasmid expressing fu ...200111507218
u(l)31 and u(l)34 proteins of herpes simplex virus type 1 form a complex that accumulates at the nuclear rim and is required for envelopment of nucleocapsids.the herpes simplex virus type 1 (hsv-1) u(l)34 protein is likely a type ii membrane protein that localizes within the nuclear membrane and is required for efficient envelopment of progeny virions at the nuclear envelope, whereas the u(l)31 gene product of hsv-1 is a nuclear matrix-associated phosphoprotein previously shown to interact with u(l)34 protein in hsv-1-infected cell lysates. for these studies, polyclonal antisera directed against purified fusion proteins containing u(l)31 protein fuse ...200111507225
cutting edge: myeloid complement c3 enhances the humoral response to peripheral viral infection.hsv-1 is the causative agent of cutaneous lesions, commonly referred to as cold sores. primary exposure to the virus ordinarily occurs through the periphery, in particular through abraded skin or mucosal membranes. under certain circumstances (e.g., in neonatals or aids patients), the infection becomes disseminated, often with severe consequences. spread of hsv-1 is limited by virus-specific ab. the development of an efficient humoral response to the virus is dependent on innate immunity compone ...200111509581
a first step toward understanding membrane fusion induced by herpes simplex virus.in this issue of molecular cell, carfí et al. present the x-ray structure of the n-terminal domains of hvea, a tnf receptor family member, in complex with herpes simplex virus gd, providing a first step to understanding the herpesvirus mode of membrane fusion.200111511354
integrating retroviral cassette extends gene delivery of hsv-1 expression vectors to dividing cells.retroviral vectors have long been used in a wide variety of gene transfer applications but have certain drawbacks, such as small cargo size, limited tropism, and low titers. hsv expression vectors overcome these disadvantages, but, because they persist in target cells as nonreplicative episomes, they are not retained in all the progeny of dividing cells. chimeric hsv/aav products that can mediate transgene integration in human mitotic cells have been constructed, but, to date, genetic modificati ...200111515376
differences in pathogenicity of herpes simplex virus serotypes 1 and 2 may be observed by histopathology and high-resolution magnetic resonance imaging in a murine encephalitis model.the mouse model for herpes simplex-induced encephalitis (hse) is an established preclinical tool for evaluating the efficacy of new therapeutic interventions. we evaluated the utility of high-resolution in vivo mri in observing the progression of experimental hse during the first week postinfection. female balb/c mice were inoculated intracerebrally with hsv-1 or hsv-2 by microinjection. each animal was evaluated daily by high-resolution (4.7 tesla) t(2) weighted mri and clinical disease scoring ...200111517383
infection and establishment of latency in the dog brain after direct inoculation of a nonpathogenic strain of herpes simplex virus-1.a number of diseases affecting the cns occur in the dog and can be used as models for gene therapy in a large brain. hsv-1 has several potential advantages as a vector to transfer genes into the cns. however, the ability of hsv-1 to infect cns cells varies among species and no information was available for the dog. when the nonpathogenic 1716 strain of hsv-1 was injected into the brains of normal dogs it established a latent infection without signs of pathology. thus, it appears to be suitable a ...200111517387
lightcycler multiplex pcr for the laboratory diagnosis of common viral infections of the central nervous system.a conventional multiplex pcr assay that detects herpes simplex virus type 1 (hsv-1), hsv-2, varicella-zoster virus, and enteroviruses for the diagnosis of central nervous system infections was modified to be performed using the lightcycler system. the sensitivity of detection of each of the viruses using the lightcycler assay was compared to that of the conventional assay using external quality assessment material. the assays had equivalent sensitivities, but the lightcycler assay was more rapid ...200111526128
direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors.biodistribution, magnitude and duration of a therapeutic transgene's expression may be assessed by linking it to the expression of a positron emission tomography (pet) reporter gene (prg) and then imaging the prg's expression by a pet reporter probe (prp) in living animals. we validate the simple approach of co-administering two distinct but otherwise identical adenoviruses, one expressing a therapeutic transgene and the other expressing the prg, to track the therapeutic gene's expression. two p ...200111526454
comparison of chemicon simulfluor direct fluorescent antibody staining with cell culture and shell vial direct immunoperoxidase staining for detection of herpes simplex virus and with cytospin direct immunofluorescence staining for detection of varicella-zoster virus.a new rapid direct immunofluorescence assay, the simulfluor direct fluorescent-antibody (dfa) assay, which can simultaneously detect herpes simplex virus types 1 and 2 (hsv-1 and -2) and varicella-zoster virus (vzv), was evaluated in comparison with our current standard procedures of (i) shell vial direct immunoperoxidase (shell vial ip) staining and cell culture for detection of hsv and (ii) cytospin dfa staining for vzv detection. a total of 517 vesicular, oral, genital, and skin lesion specim ...200111527802
acute effects of purified and uv-inactivated herpes simplex virus type 1 on the hypothalamo-pituitary-adrenocortical axis.herpes simplex virus type 1 (hsv-1) is a common cause of viral encephalitis, manifested by neuroendocrine and behavioral changes. we have previously demonstrated that hsv-1 induces marked hypothalamo-pituitary-adrenocortical (hpa) axis activation. in this study we characterized the acute effects of hsv-1 on the hpa axis occurring before viral replication and appearance of clinical signs of encephalitis. since in previous studies we used crude virus preparations which may contain immune factors p ...200111528217
activation of interferon response factor-3 in human cells infected with herpes simplex virus type 1 or human cytomegalovirus.activation of cellular interferon-stimulated genes (isgs) after infection with herpes simplex virus type 1 (hsv-1) or human cytomegalovirus (hcmv) was investigated. the level of isg54-specific rna in human fetal lung (hfl) or human foreskin (bj) fibroblasts increased substantially after infection with either virus in the presence of cycloheximide. hsv-1 particles lacking glycoprotein d or glycoprotein h failed to induce isg54-specific rna synthesis, demonstrating that entry of virus particles ra ...200111533154
direct and sensitive detection of a human virus by rupture event scanning.we have developed a sensitive, economical method that directly detects viruses by making use of the interaction between type 1 herpes simplex virus (hsv1) and specific antibodies covalently attached to the oscillating surface of a quartz crystal microbalance (qcm). the virions were detached from the surface by monotonously increasing the amplitude of oscillation of the qcm, while using the qcm to sensitively detect the acoustic noise produced when the interactions were broken. we term this proce ...200111533641
polymerase chain reaction as a diagnostic adjunct in herpesvirus infections of the nervous system.polymerase chain reaction (pcr) is a powerful technique that allows detection of minute quantities of dna or rna in cerebrospinal fluid (csf), vesicle and endoneurial fluids, blood, fresh-frozen, and even formalin-fixed tissues. various infectious agents can be detected with high specificity and sensitivity, including bacteria, parasites, rickettsia and viruses. pcr analysis of csf has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesvirus ...200111556691
a kinetic analysis of substrate recognition by uracil-dna glycosylase from herpes simplex virus type 1.uracil-dna glycosylase (udg) is responsible for the removal of uracil from dna. it has previously been demonstrated that udg exhibits some sequence dependence in its activity, although this has not been well characterised. this study has investigated the sequence-dependent activity of udg from herpes simplex virus type-1 (hsv-1). a more detailed analysis has been possible by using both kinetic and binding assays with a variety of different oligonucleotide substrates. the target uracil has been p ...200111557818
[aetiopathogenesis of bell's idiopathic peripheral facial palsy].bell's facial palsy is a common condition with an incidence varying between 11.5 and 40.2 cases per 100,000 persons per year. however, some aspects of its aetiopathogenesis are still not clear.200111562829
acyclic/carbocyclic guanosine analogues as anti-herpesvirus agents.several guanosine analogues, i.e. acyclovir (and its oral prodrug valaciclovir), penciclovir (in its oral prodrug form, famciclovir) and ganciclovir, are widely used for the treatment of herpesvirus [i.e. herpes simplex virus type 1 (hsv-1), and type 2 (hsv-2), varicella-zoster virus (vzv) and/or human cytomegalovirus (hcmv)] infections. in recent years, several new guanosine analogues have been developed, including the 3-membered cyclopropylmethyl and -methenyl derivatives (a-5021 and synguanol ...200111563039
seroprevalence of herpes simplex virus types 1 and 2 in hiv-infected and uninfected homosexual men in a primary care setting.genital herpes is usually caused by herpes simplex virus type 2 (hsv-2), with infections often being unrecognised by patients and/or clinicians. hsv-2 infections may be a risk factor for the transmission of human immunodeficiency virus (hiv) infection. reliable tests for type-specific hsv antibodies are now readily available.200111564596
generation of adenoviruses encoding the herpes simplex virus vhs gene: a novel strategy to generate adenoviruses expressing genes toxic to producer cells.adenovirus vectors expressing suicide genes represent a promising approach for cancer gene therapy. we wanted to determine whether the virion host shutoff (vhs) gene of herpes simplex virus could be used as a suicide gene for gene therapy of glioblastomas. the vhs gene was cloned downstream of the glial fibrillary acidic protein promoter to direct tissue-specific expression, and recombinant adenoviruses were generated in 293 cells. viruses, which contained the vhs gene but did not express it, co ...200111571534
adenovirus-mediated expression of hsv1-tk or fas ligand induces cell death in primary human glioma-derived cell cultures that are resistant to the chemotherapeutic agent ccnu.due to minimal treatment success with surgery, radiotherapy, and chemotherapy, the aim of this study was to test the therapeutic potential of gene therapy for the treatment of glioblastoma multiforme (gbm). we have quantitatively analyzed two gene therapy approaches using short-term human glioma cell cultures derived from surgical biopsies (designated in859, in1612, in2045, in1760, and in1265) and compared the results of gene therapy with the chemosensitivity of the same cells. all of the glioma ...200111571537
complement c4 deficiency and hla homozygosity in patients with frequent intraoral herpes simplex virus type 1 infections.three consecutive patients with no apparent immunodeficiency who had frequent intraoral herpes simplex type 1 recurrences, a rare complication of herpes simplex virus infection, were found to have a total deficiency of either the a or b isotype of the complement component c4 and to be homozygous for the studied hla antigens. a combination of hla homozygosity, which may lead to impaired t cell recognition of viral peptides, and deficiency in the classical complement pathway, which can compromise ...200111577377
a null mutation in the gene encoding the herpes simplex virus type 1 ul37 polypeptide abrogates virus maturation.the tegument is an integral and essential structural component of the herpes simplex virus type 1 (hsv-1) virion. the ul37 open reading frame of hsv-1 encodes a 120-kda virion polypeptide which is a resident of the tegument. to analyze the function of the ul37-encoded polypeptide a null mutation was generated in the gene encoding this protein. in order to propagate this mutant virus, transformed cell lines that express the ul37 gene product in trans were produced. the null mutation was transferr ...200111581394
multiple herpetic whitlow lesions in a 4-year-old girl: case report and review of the literature.herpetic whitlow is a herpes simplex virus type 1 or 2 infection of the fingers characterised by erythema and painful, non-purulent vesicles. in children it typically occurs after auto-inoculation from herpes stomatitis, herpes labialis or genitalis. occasionally, person-to-person transmission occurs from family members with herpes labialis. we report a 4-year-old girl with multiple herpetic whitlows secondary to herpetic stomatitis and present a review of the medical literature based on a syste ...200111585074
primary graft failure caused by herpes simplex virus type 1. 200111588438
combination vascular delivery of herpes simplex oncolytic viruses and amplicon mediated cytokine gene transfer is effective therapy for experimental liver cancer.herpes simplex type i (hsv)-based vectors have been used experimentally for suicide gene therapy, immunomodulatory gene delivery, and direct oncolytic therapy. the current study utilizes the novel concept of regional delivery of an oncolytic virus in combination with or serving as the helper virus for packaging herpes-based amplicon vectors carrying a cytokine transgene, with the goal of identifying if this combination is more efficacious than either modality alone.200111591892
immunohistological study of infiltrated cells and cytokines in murine herpetic keratitis.to identify localization and kinetics of infiltrated cells and cytokines in murine herpetic keratitis.200111594984
comparison of different forms of herpes simplex replication-defective mutant viruses as vaccines in a mouse model of hsv-2 genital infection.some subunit vaccines composed of herpes simplex virus (hsv) glycoproteins have been shown to protect guinea pigs against primary and recurrent genital infection by hsv-2. however, these vaccines were ineffective or only marginally effective in clinical trials. to attempt to define an animal model that would better discriminate the protective capacity of different vaccine formulations, we have examined the requirements for vaccine-induced protection against hsv-2 infection and disease in a mouse ...200111601897
mycobacterial and nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus infection: a prospective, cohort study.a prospective observational study was done to describe nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus (hiv) infection.200111602023
temporal regulation of herpes simplex virus type 2 vp22 expression and phosphorylation.the vp22 protein of herpes simplex virus type 2 (hsv-2) is a major component of the virion tegument. previous work with hsv-1 indicated that vp22 is phosphorylated during infection, and phosphorylation may play a role in modulating vp22 localization in infected cells. it is not clear, however, when phosphorylation occurs in infected cells or how it is regulated. less is known about the synthesis and phosphorylation of hsv-2 vp22. to study the complete biosynthetic history of hsv-2 vp22, we gener ...200111602713
characterization of the dna polymerase gene of varicella-zoster viruses resistant to acyclovir.the nucleotide changes of the dna polymerase gene and the susceptibility of acyclovir (acv)-resistant varicella-zoster virus (vzv) mutants to anti-herpetic drugs were determined and compared to those of herpes simplex virus type 1 (hsv-1) mutants. the seven acv-resistant vzv mutants were classified into three groups, n(779)s, g(805)c and v(855)m, according to the sequences of their dna polymerase genes. the amino acid substitutions n(779)s and g(805)c were identical in position to the n(815)s an ...200111602787
reduced rates of gene loss, gene silencing, and gene mutation in dnmt1-deficient embryonic stem cells.tumor suppressor gene inactivation is a crucial event in oncogenesis. gene inactivation mechanisms include events resulting in loss of heterozygosity (loh), gene mutation, and transcriptional silencing. the contribution of each of these different pathways varies among tumor suppressor genes and by cancer type. the factors that influence the relative utilization of gene inactivation pathways are poorly understood. in this study, we describe a detailed quantitative analysis of the three major gene ...200111604495
a combination vaccine confers full protection against co-infections with influenza, herpes simplex and respiratory syncytial viruses.combined/composite vaccines should be useful in reducing the number of vaccinations and provide more flexibility in confronting biological warfare scenarios. we tested the effectiveness of a composite genetic vaccine designed from previously known protective antigens directed against influenza a virus (inf-a), herpes simplex virus type-1 (hsv-1) and respiratory syncytial virus (rsv) in a mouse-based challenge. immunizing mice with a pool of four plasmids; inf-a haemagglutinin (ha), inf-a nucleop ...200111672920
detection of mutations within the thymidine kinase gene of herpes simplex virus type 1 by denaturing gradient gel electrophoresis.denaturing gradient gel electrophoresis has been applied widely for the detection of mutation(s) and polymorphisms of various genes. it is shown that this system is also feasible for analyzing mutations in the thymidine kinase (tk) gene of herpes simplex virus type 1 (hsv-1). thus, this system is applicable for examining whether a drug-resistant hsv-1 contains a tk mutation(s) or otherwise. this system can also be useful for detecting heterogeneity and the emergence of drug-resistant mutants in ...200211684298
vaccination prevents latent hsv1 infection of mouse brain.herpes simplex encephalitis (hse) is a rare but very serious disorder caused by herpes simplex type 1 virus (hsv-1). treatment with acyclovir decreases mortality but many patients still suffer cognitive impairment subsequently. a vaccine against hsv1 would therefore be of great value. hsv-1 has been implicated also in alzheimer's disease (ad): we established that hsv1 resides in the brain of about two thirds of ad patients and aged normal people, and that in carriers of the type 4 allele of the ...200111705626
potential for hsv-1 vaccination to reduce risk of hsv-1 encephalitis and/or alzheimer's disease? 200111705628
fluorescent tricyclic analogues of acyclovir and ganciclovir. a structure-antiviral activity study.of a series of new guanine base modified tricyclic analogues of acyclovir (acv, 1) and ganciclovir (gcv, 2), derivatives of the 3,9-dihydro-9-oxo-5h-imidazo[1,2-a]purine system, evaluated for activity against herpes simplex virus type 1 and 2, several fluorescent analogues, 6-(4-meoph)-tacv (8), 7-me-6-ph-tacv (17), 6-(4-meoph)-tgcv (27), and 7-me-6-ph-tgcv (28), were obtained that showed similar potency and selectivity as the parent compounds. the activity was found to be strongly dependent on ...200111708929
monitoring gene therapy with reporter gene imaging.rapid advances in imaging technologies and gene transfer strategies offer a great opportunity to optimize clinical trials of human gene therapy. reporter genes are emerging as very powerful tools to monitor the delivery, magnitude, and time variation of therapeutic gene transfer in vivo. several reporter genes, such as the herpes simplex virus type 1 thymidine kinase, the dopamine type 2 receptor, and the somatostatin receptor type 2, are currently being successfully used with gamma camera, sing ...200111710773
possible iatrogenic transmission of creutzfeldt-jakob disease via tonometer tips: a review of the literature.tonometer tips are used by optometrists to measure intraocular pressures. the recommended procedure of soaking in bleach solution kills bacteria and certain viruses, such as human immunodeficiency virus, herpes simplex virus-1 and herpes simplex virus-2, adenovirus 8, and hepatitis b, from the tip. conversely, recommendations made in literature to sterilize equipment that may have come in contact with virus-contaminated tissue from patients with creutzfeldt-jakob disease have a somewhat tougher ...200111712632
gene transfer to ovine corneal endothelium.modification of a donor cornea by gene therapy has potential to modulate irreversible rejection, the major cause of corneal graft failure. the sheep is a useful model for the human in this respect, as ovine endothelial cells are amitotic. the aim of the study was to investigate the ability of various non-viral and viral agents to transfer a reporter gene to ovine corneal endothelium.200111720159
laboratory diagnosis of common herpesvirus infections of the central nervous system by a multiplex pcr assay.a sensitive multiplex pcr assay for single-tube amplification that detects simultaneous herpes simplex virus type 1 (hsv-1), herpes simplex virus type 2 (hsv-2), varicella-zoster virus (vzv), human cytomegalovirus (cmv), and epstein-barr virus (ebv) is reported with particular emphasis on how the method was optimized and carried out and its sensitivity was compared to previously described assays. the assay has been used on a limited number of clinical samples and must be thoroughly evaluated in ...200111724856
herpes-simplex-virus-infected cells produce a protein that binds to the tar dna region of the human immunodeficiency virus type 1 long terminal repeat.activation of human immunodeficiency virus type 1 (hiv-1) provirus by herpes simplex virus type 1 (hsv-1) infection is mediated by both hsv-1 gene products and cellular transactivators. previously, several key factors such as nf-kappab-specific proteins p55 and p85, hlp-1 protein that binds to the lbp-1 sequences of the hiv-1 long terminal repeat (ltr) and the viral transactivator icpo were found to play a role in the transcriptional activation of hiv-1 ltr expression. in this report, we describ ...199411725028
topical application of the cornea post-infection with plasmid dna encoding interferon-alpha1 but not recombinant interferon-alphaa reduces herpes simplex virus type 1-induced mortality in mice.a study was undertaken to compare the efficacy of recombinant interferon (rifn)-alphaa to plasmid dna encoding ifn-alpha1 against ocular herpes simplex virus type 1 (hsv-1) infection. the topical application of rifn-alphaa (100-300 units/eye) onto the cornea of mice subsequently infected 24 h later with hsv-1 antagonized viral-induced mortality. the enhancement in cumulative survival in the rifn-alphaa-treated mice correlated with a reduction of viral titers recovered in the eye and trigeminal g ...200111730939
[fulminant acute retinal necrosis 10 months after ipsilateral herpes simplex virus encephalitis - a case report].cases of acute retinal necrosis caused by herpes simplex virus are rare. we present here a case with a very fast progression 10 months after a primary herpetic encephalitis in an immunocompetent patient.200111731902
transverse myelitis associated with herpes simplex virus infection.the case of an otherwise healthy 6-year-old boy with symptoms and signs of acute transverse myelitis is presented. the diagnosis was confirmed by magnetic resonance imaging. an episode of gingivostomatitis had preceded, and serology indicated herpes simplex virus type 1 infection. the child recovered gradually, and no relapses were noted during a 30-month follow-up period.200111732777
the synthesis and biological evaluation of novel bridging nucleoside analogues.novel bridging nucleoside analogues were prepared by cycloaddition reactions between pyranose glycals and barbiturate-derived, reactive thionoimides in modest yields. in all of the reactions conducted, the major cycloadducts obtained were the bottom faced adducts resulting from endo addition to the glycal. the adducts were stable to a variety of acidic reaction conditions and several of the compounds showed moderate activities against hiv-1 in primary human lymphocytes. one compound displayed an ...200211741776
killing effects of ganciclovir on human pulmonary adenocarcinoma cell a549 transduced with hsv1-tk gene in vitro and in vivo.to observe the killing effects of ganciclovir (gcv) on the human pulmonary adenocarcinoma cell a549 transduced with herpes simplex virus i type thymine kinase (hsv1-tk) gene in vitro and in vivo.200111749772
treatment of malignant gliomas with a replicating adenoviral vector expressing herpes simplex virus-thymidine kinase.we evaluated the interaction between oncolytic, replication-competent adenoviral vectors and the herpes simplex virus-1 thymidine kinase (hsv1-tk) gene/ganciclovir (gcv) suicide system for the treatment of malignant gliomas. we constructed a panel of replication-competent adenoviral vectors in which the luciferase (ig.ad5e1(+). e3luc) or hsv1-tk gene (ig.ad5e1(+).e3tk) replace the m(r) 19,000 glycoprotein (gp19k) coding sequence in the e3 region. ig.ad5e1. ig.ad5.clipluc and ig.adapt.tk are e1-d ...200111751394
u(s)3 protein kinase of herpes simplex virus 1 blocks caspase 3 activation induced by the products of u(s)1.5 and u(l)13 genes and modulates expression of transduced u(s)1.5 open reading frame in a cell type-specific manner.the coding domain of the herpes simplex virus type 1 (hsv-1) alpha22 gene encodes two proteins, the 420-amino-acid infected-cell protein 22 (icp22) and u(s)1.5, a protein colinear with the carboxyl-terminal domain of icp22. in hsv-1-infected cells, icp22 and u(s)1.5 are extensively modified by the u(l)13 and u(s)3 viral protein kinases. in this report, we show that in contrast to other viral proteins defined by their properties as alpha proteins, u(s)1.5 becomes detectable and accumulated only a ...200211752164
monoclonal antibodies and human sera directed to the secreted glycoprotein g of herpes simplex virus type 2 recognize type-specific antigenic determinants.glycoprotein g-2 (gg-2) of herpes simplex virus type 2 (hsv-2) is cleaved to a secreted amino-terminal portion (sgg-2) and to a cell-associated carboxy-terminal portion which is further o-glycosylated to constitute the mature gg-2 (mgg-2). in contrast to mgg-2, which is known to elicit a type-specific antibody response in the human host, information on the immunogenic properties of sgg-2 is lacking. here the sgg-2 protein was purified on a heparin column and used for production of monoclonal ant ...200211752712
herpes simplex virus type 1 associated acute retinal necrosis following encephalitis. 200111756904
[temperature sensitive mutant of herpes simplex virus type 1. i. pathogenicity and immunogenicity].the aim of the study was to characterize biological features of the sensitive mutant of hsv-1, derived from mcintyre strain by numerous virus passages at lowered replication temperature (28 degrees c). pathogenicity of obtained ts mutant for inbred mice lines, cfw/pzh and balb/cpzh, was determined. statistically significant decrease in virulence of the mutant for these mouse lines was demonstrated, as compared with the native virus strain, propagated at 37 degrees c. immunogenic activity of ts m ...200111757407
molecular targeting of gene therapy and radiotherapy.the full promise of gene therapy has been limited by the lack of specificity of vectors for tumor tissue as well as the lack of antitumor efficacy of transgenes encoded by gene delivery systems. in this paper we review our studies investigating two modifications of gene therapy combined with radiotherapy. the first investigations described include studies of radiation inducible gene therapy. in this paradigm, radio-inducible dna sequences from the carg elements of the egr-1 promoter are cloned u ...200111765068
inhibition of apoptosis by primary isolates of herpes simplex virus.hsv-1 inhibits apoptosis of the infected cell, presumably to increase viral yield. weaker anti-apoptotic activity was previously reported in laboratory-adapted hsv-2, but not in two low-passage clinical hsv-2 isolates, suggesting that the anti-apoptotic effect might result from adaptation to laboratory growth. we therefore assembled a large panel of clinical strains of hsv-1 and hsv-2. clinical and laboratory strains of hsv-1 strongly inhibited apoptosis of jurkat cells, as determined by morphol ...200111765923
reflex and steady state tears in patients with latent stromal herpetic keratitis.to compare tear production in patients with stromal herpetic keratitis with that in healthy control subjects.200211773017
second-site mutation outside of the u(s)10-12 domain of deltagamma(1)34.5 herpes simplex virus 1 recombinant blocks the shutoff of protein synthesis induced by activated protein kinase r and partially restores neurovirulence.earlier studies have shown that herpes simplex virus type 1 (hsv-1) activated protein kinase r (pkr) but that the product of the product of the gamma(1)34.5 gene binds and redirects the host phosphatase 1 to dephosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eif-2alpha). in consequence, the gamma(1)34.5 gene product averts the threatened shutoff of protein synthesis caused by activated pkr. serial passages of deltagamma(1)34.5 mutants in human cells led to isolation ...200211773369
a gene capable of blocking apoptosis can substitute for the herpes simplex virus type 1 latency-associated transcript gene and restore wild-type reactivation levels.after ocular herpes simplex virus type 1 (hsv-1) infection, the virus travels up axons and establishes a lifelong latent infection in neurons of the trigeminal ganglia. lat (latency-associated transcript), the only known viral gene abundantly transcribed during hsv-1 neuronal latency, is required for high levels of reactivation. the lat function responsible for this reactivation phenotype is not known. recently, we showed that lat can block programmed cell death (apoptosis) in neurons of the tri ...200211773398
spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice.infection of the mouse trigeminal ganglia (tg) is the most commonly used model for the study of herpes simplex virus type 1 (hsv-1) latency. its popularity is caused, at least in part, by the perception that latent infection can be studied in this system in the absence of spontaneous viral reactivation. however, this perception has never been rigorously tested. to carefully study this issue, the eyes of swiss-webster mice were inoculated with hsv-1 (kos), and 37-47 days later the tg were dissect ...200211773630
local inflammation and devascularization--in vivo mechanisms of the "bystander effect" in vpc-mediated hsv-tk/gcv gene therapy for human malignant glioma.somatic gene therapy with the herpes simplex virus type i thymidine kinase gene/ganciclovir (hsv-tk/gcv) system and murine retroviral vector producer cells (vpcs) was introduced as a new adjuvant treatment modality to treat tumor bulk and to prevent tumor recurrence in patients harboring malignant glioma. the single-center experience after treatment of 27 patients undergoing tumor resection followed by intracerebral vpc injection for hsv-tk suicide gene therapy will be presented focused on findi ...200111773974
experimental herpes simplex virus encephalitis: inhibition of the expression of inducible nitric oxide synthase in mouse brain tissue.in the brain tissue of 36 mice infected with herpes simplex virus type 1, strain f, we determined the expression of inducible nitric oxide synthase (inos) with semiquantitative reverse transcription polymerase chain reaction. the viral burden was quantitated by polymerase chain reaction. nitric oxide, induced by inos, may contribute to neuronal cell damage following virus infection. as the experimental therapeutic strategy in herpes simplex virus encephalitis (hsve), we used: n-nitro-l-arginin ( ...200211786216
importance of c-terminus of herpes simplex virus type 1 thymidine kinase for maintaining thymidine kinase and acyclovir-phosphorylation activities.we previously isolated an acyclovir (acv)-resistant herpes simplex virus type 1 (hsv-1), strain tar, from a child with wiskott-aldrich syndrome. an acyclovir-sensitive hsv-1, strain tas, had been isolated from the same patient before the isolation of hsv-1 tar. the tk protein of acv-sensitive hsv-1 tas was composed of 376 amino acids, while that of hsv-1 tar was composed of 407 amino acids with altered amino acid residue between positions 355-407. the elongation of tk was caused by a single nucl ...200211793392
herpes simplex virus icp0 and icp34.5 counteract distinct interferon-induced barriers to virus replication.interferon inhibits virus replication through multiple mechanisms. here we show that herpes simplex virus proteins icp0 and icp34.5 overcome interferon-induced barriers to viral transcription and translation, respectively. these cytokine-induced antiviral mechanisms are differentially expressed in established cell lines: u2os cells do not mount the ifn-induced mechanism targeted by icp0, and vero cells may be defective for the mechanism targeted by icp34.5.200211799195
terminally repeated sequences on a herpesvirus genome are deleted following circularization but are reconstituted by duplication during cleavage and packaging of concatemeric dna.the mechanisms underlying cleavage of herpesvirus genomes from replicative concatemers are unknown. evidence from herpes simplex virus type 1 suggests that cleavage occurs by a nonduplicative process; however, additional evidence suggests that terminal repeats may also be duplicated during the cleavage process. this issue has been difficult to resolve due to the variable numbers of reiterated terminal repeats that the herpes simplex virus type 1 genome can contain. guinea pig cytomegalovirus is ...200211799198
herpes simplex virus 1-infected cell protein 0 contains two e3 ubiquitin ligase sites specific for different e2 ubiquitin-conjugating enzymes.infected cell protein 0 (icp0) of herpes simplex virus 1, a multifunctional ring finger protein, enhances the expression of genes introduced into cells by infection or transfection, interacts with numerous cellular and viral proteins, and is associated with the degradation of several cellular proteins. sequences encoded by exon 2 of icp0 (residues 20-241) bind the ubch3 (cdc34) ubiquitin-conjugating enzyme, and its carboxy terminus expresses a ubiquitin ligase activity demonstrable by polyubiqui ...200211805320
herpes simplex virus type 1 glycoprotein c is necessary for efficient infection of chondroitin sulfate-expressing gro2c cells.the role of glycoprotein c (gc) for binding of herpes simplex virus type 1 (hsv-1) to cell surface chondroitin sulfate (cs) and the consequences of this interaction for virus attachment and infectivity were studied. to this end, a panel of hsv-1 gc mutants, including a gc-negative (gc(-)) variant, and mouse fibroblasts expressing either cell surface cs or heparan sulfate (hs) were used. comparing gc-positive (gc(+)) and gc(-) viruses in terms of their attachment to and infection of cs-expressing ...200211807221
cytokine expression in murine corneas during recurrent herpetic stromal keratitis.recurrent herpetic stromal keratitis (hsk) is a potentially blinding, immune-mediated disease. to better understand the immunopathology of recurrent hsk, we examined the cytokine profile of mouse corneas with the condition.200111815888
corneal herpes simplex virus type 1 superinfection in patients with recrudescent herpetic keratitis.herpetic keratitis is a common sequel of a corneal infection with herpes simplex virus (hsv)-1. recrudescent herpetic keratitis (rhk) may result in irreversible damage to the cornea. recurrences may be caused by reactivation of endogenous hsv-1 or reinfection with exogenous hsv-1. the objective of this study was to determine the incidence and risk factors involved of hsv-1 superinfection in patients with rhk.200211818377
antiviral isoflavonoid sulfate and steroidal glycosides from the fruits of solanum torvum.the c-4 sulfated isoflavonoid, torvanol a (1), and the steroidal glycoside, torvoside h (3), together with the known glycoside, torvoside a (2), were isolated from a meoh extract of solanum torvum fruits. upon enzymatic hydrolysis with beta-glucosidase, torvoside a (2) and torvoside h (3) yielded the corresponding acetal derivatives 4 and 5, respectively. torvanol a (1), torvoside h (3) and compound 5 exhibited antiviral activity (herpes simplex virus type 1) with ic(50) values of 9.6, 23.2 and ...200211830167
the acidic amino-terminal region of varicella-zoster virus open reading frame 4 protein is required for transactivation and can functionally replace the corresponding region of herpes simplex virus icp27.both varicella-zoster virus open reading frame 4 (orf4) protein and its herpes simplex virus type 1 homolog icp27 have highly acidic amino-terminal regions and cysteine-rich carboxy-terminal regions. to investigate the functional domains of these proteins, mutants were constructed and their transregulatory functions were tested in transient expression assays using two reporter plasmids, ptk-cat-sv40a and ptk-cat-syna, containing the same promoter sequences but different mrna processing signals. ...199511831723
in vitro strand exchange promoted by the herpes simplex virus type-1 single strand dna-binding protein (icp8) and dna helicase-primase.the genome of herpes simplex virus type-1 undergoes a high frequency of homologous recombination in the absence of a virus-encoded reca-type protein. we hypothesized that viral homologous recombination is mediated by the combined action of the viral single strand dna-binding protein (icp8) and helicase-primase. our results show that icp8 catalyzes the formation of recombination intermediates (joint molecules) between circular single-stranded acceptor and linear duplex donor dna. joint molecules ...200211832483
the herpes simplex virus type 1 u(s)11 protein interacts with protein kinase r in infected cells and requires a 30-amino-acid sequence adjacent to a kinase substrate domain.the herpes simplex virus type 1 gamma(1)34.5 gene product precludes the host-mediated protein shutoff response induced by activated protein kinase r (pkr). earlier studies demonstrated that recombinant viruses lacking the gamma(1)34.5 gene (deltagamma(1)34.5) developed secondary mutations that allowed earlier u(s)11 expression and enabled continued protein synthesis. further, in vitro studies demonstrated that a recombinant expressed u(s)11 protein binds pkr, blocks the phosphorylation of the al ...200211836380
altering the expression kinetics of vp5 results in altered virulence and pathogenesis of herpes simplex virus type 1 in mice.while many herpes simplex virus (hsv) structural proteins are expressed with strict-late kinetics, the hsv virion protein 5 (vp5) is expressed as a "leaky-late" protein, such that appreciable amounts of vp5 are made prior to dna replication. our goal has been to determine if leaky-late expression of vp5 is a requirement for a normal hsv infection. it had been shown previously that recombinant viruses in which the vp5 promoter was replaced with promoters of other kinetic classes (including a stri ...200211836397
neurons differentially activate the herpes simplex virus type 1 immediate-early gene icp0 and icp27 promoters in transgenic mice.herpes simplex virus type 1 (hsv-1) immediate-early (ie) proteins are required for the expression of viral early and late proteins. it has been hypothesized that host neuronal proteins regulate expression of hsv-1 ie genes that in turn control viral latency and reactivation. we investigated the ability of neuronal proteins in vivo to activate hsv-1 ie gene promoters (icp0 and icp27) and a late gene promoter (gc). transgenic mice containing ie (icp0 and icp27) and late (gc) gene promoters of hsv- ...200211836423
a herpes simplex virus type 1 mutant with gamma 34.5 and lat deletions effectively oncolyses human u87 glioblastomas in nude mice.we previously constructed a novel recombinant herpes simplex virus with deletions in the gamma 34.5 and lat genes. lat was replaced by the gene for green fluorescent protein, to allow monitoring of viral transduction in vitro and in vivo. we previously confirmed that this virus, designated dm33, retains its oncolytic properties in vitro and is inhibited with respect to spontaneous reactivation. the objective of this study was to demonstrate the therapeutic efficiency of this virus in the treatme ...200211841729
expression of hepatitis c virus envelope glycoproteins by herpes simplex virus type 1-based amplicon vectors.herpes simplex virus type 1 (hsv-1)-based amplicon vectors expressing hepatitis c virus (hcv) e1 and e2 glycoproteins were investigated. hsv-1 amplicon vectors carrying the e1e2p7- or e2p7-coding sequences of hcv type 1a under the control of the hsv-1 ie4 (alpha22/alpha47) promoter were constructed. studies of infected hepg2, wrl 68 or vero cells indicated that hsv-1-based amplicon vectors express high levels of hcv glycoproteins that are processed correctly. immunofluorescence microscopy combin ...200211842251
the use of a genetically engineered herpes simplex virus (r7020) with ionizing radiation for experimental hepatoma.the herpes simplex virus (hsv) recombinant virus r7020 is an attenuated virus designed as a candidate for immunization against both hsv-1 and hsv-2 infections. it was extensively tested in an experimental animal system and in a healthy human adult population without significant untoward effects. we report on the use of r7020 with ionizing radiation as an oncolytic agent for hepatomas. two hepatoma cell lines were studied, hep3b and huh7. r7020 replicated to higher titers in hep3b cells than in h ...200211850725
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