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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
selective nonpeptidic inhibitors of herpes simplex virus type 1 and human cytomegalovirus proteases.the proteases encoded by herpesviruses including herpes simplex virus type 1 (hsv-1) and human cytomegalovirus (hcmv) are attractive targets for antiviral drug development because of their important roles in viral replication. we randomly screened a chemical compound library for inhibitory activity against hsv-1 protease. 1,4-dihydroxynaphthalene and three naphthoquinones were found to be potent inhibitors of hsv-1 protease with ic50 values of 6.4 to 16.9 microm. inhibitory mode analysis of the ...200111256477
region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture.the latency-associated transcript (lat) is the only abundant herpes simplex virus type 1 (hsv-1) transcript expressed during latency. in the rabbit eye model, lat null mutants do not reactivate efficiently from latency. we recently demonstrated that the lat null mutant dlat2903 induces increased levels of apoptosis in trigeminal ganglia of infected rabbits compared to lat+ strains (g.-c. perng, c. jones, j. ciacci-zarella, m. stone, g. henderson, a. yokht, s. m. slanina, f. m. hoffman, h. ghiasi ...200111264353
alaarg motif in the carboxyl terminus of the gamma(1)34.5 protein of herpes simplex virus type 1 is required for the formation of a high-molecular-weight complex that dephosphorylates eif-2alpha.the gamma(1)34.5 protein of herpes simplex virus (hsv) type 1 functions to prevent the shutoff of protein synthesis mediated by the double-stranded-rna-dependent protein kinase pkr. this is because gamma(1)34.5 associates with protein phosphatase 1 (pp1) through its carboxyl terminus, forming a high-molecular-weight complex that dephosphorylates the alpha subunit of translation initiation factor eif-2 (eif-2alpha). here we show that val193glu and phe195leu substitutions in the pp1 signature moti ...200111264356
human neuron-committed teratocarcinoma nt2 cell line has abnormal nd10 structures and is poorly infected by herpes simplex virus type 1.herpes simplex virus type 1 (hsv-1) immediate-early regulatory protein icp0 stimulates the initiation of lytic infection and reactivation from quiescence in human fibroblast cells. these functions correlate with its ability to localize to and disrupt centromeres and specific subnuclear structures known as nd10, pml nuclear bodies, or promyelocytic oncogenic domains. since the natural site of herpesvirus latency is in neurons, we investigated the status of nd10 and centromeres in uninfected and i ...200111264371
identification of herpes simplex virus genital infection: comparison of a multiplex pcr assay and traditional viral isolation techniques.genital herpes simplex virus (hsv) is of major public health importance, as indicated by the marked increase in the prevalence of genital herpes over the past two decades. viral culture has traditionally been regarded as the gold standard for diagnosis. in this study, we compared viral culture and the amplification of hsv dna by the polymerase chain reaction (pcr) with respect to sensitivity, cost, clinical utility, and turnaround time. patient sample swabs from 100 individuals were inoculated o ...200111266519
herpes simplex virus 1 transmission through corneal transplantation.genetic characterisation of herpes simplex virus type 1 (hsv-1) dna isolated from a donor cornea before and after corneal transplantation demonstrated the transmission of hsv-1 through transplantation. this study is the first to provide conclusive evidence for the transmission of hsv-1 by penetrating keratoplasty with subsequent reactivation of donor-derived hsv-1 in the transplanted cornea.200111273067
porcine hvec, a member of the highly conserved hvec/nectin 1 family, is a functional alphaherpesvirus receptor.human herpesvirus entry mediator c (hvec) is an alphaherpesvirus receptor which binds to virion glycoprotein d (gd). we identified porcine hvec and studied its interaction with pseudorabies virus (prv) and herpes simplex virus type 1 (hsv-1) gd. porcine and human hvec have 96% amino acid identity and hvec from african green monkey, mouse, hamster, and cow are similarly conserved. porcine hvec mediates entry of hsv-1, hsv-2, prv, and bovine herpesvirus type 1. truncated soluble forms of hsv-1 and ...200111277703
ability of the tat basic domain and vp22 to mediate cell binding, but not membrane translocation of the diphtheria toxin a-fragment.a number of proteins are able to enter cells from the extracellular environment, including protein toxins, growth factors, viral proteins, homeoproteins, and others. many such translocating proteins, or parts of them, appear to be able to carry with them cargo into the cell, and a basic sequence from the hiv-1 tat protein has been reported to provide intracellular delivery of several fused proteins. for evaluating the efficiency of translocation to the cytosol, this tat-peptide was fused to the ...200111284691
herpesvirus infection of seborrheic keratoses.we present three examples of patients with seborrheic keratoses complicated by necrotizing herpesvirus infection. two patients had localized cutaneous herpetic infections, and the third patient had a generalized cutaneous herpesvirus infection. two of the lesions were thought to be squamous cell carcinoma. the third was clinically identified as inflamed seborrheic keratosis. herpesvirus infection was not clinically suspected in two of the patients. the histologic changes were similar in all case ...200111285412
prevalence and risk factors of hsv-1 and hsv-2 antibodies in european hiv infected women.to investigate the prevalence and risk factors of hsv-1 and hsv-2 antibodies in hiv infected women and the association between recurrent genital ulcerations and hiv disease progression in hsv-2 positive women.200111287691
experimental laser-assisted in situ keratomileusis induces the reactivation of latent herpes simplex virus.we determined whether laser-assisted in situ keratomileusis acts as a trigger for the reactivation and ocular shedding of herpes simplex virus type-1 in a rabbit latency model.200111292417
biological purging of breast cancer cells using an attenuated replication-competent herpes simplex virus in human hematopoietic stem cell transplantation.autologous hematopoietic stem cell transplantation after myelosuppressive chemotherapy is used for the treatment of high-risk breast cancer and other solid tumors. however, contamination of the autologous graft with tumor cells may adversely affect outcomes. human hematopoietic bone marrow cells are resistant to herpes simplex virus type 1 (hsv-1) replication, whereas human breast cancer cells are sensitive to hsv-1 cytotoxicity. therefore, we examined the utility of g207, a safe replication-com ...200111306480
a novel antivirally active fucan sulfate derived from an edible brown alga, sargassum horneri.a novel fucan sulfate (hor-1) was isolated from the hot water extract of an edible brown alga, sargassum horneri (turner) c. agardh. the fucan sulfate was revealed to have sugar linkage types, sulfate content and uronic acid content different from those of sodium hornan (na-hor), another fucan sulfate isolated from this alga. however, it exhibited inhibitory activity against replication of herpes simplex virus type 1 with similar potency to na-hor.200111310680
antitumor agents. 207. design, synthesis, and biological testing of 4beta-anilino-2-fluoro-4'-demethylpodophyllotoxin analogues as cytotoxic and antiviral agents.2-fluoropodophyllotoxin (11) and several 4beta-anilino-2-fluoro-4'-o-demethyl analogues were synthesized and evaluated in both antineoplastic and antiviral assays. these compounds were moderately active against some cancer cell lines, but they were less active than the corresponding nonfluorinated analogues. compound 11 exhibited the best activity against kb carcinoma with a gi(50) of approximately 30 nm. most compounds exhibited moderate activity against hcmv with id(50) and id(90) values in th ...200111311065
two paths for dissemination of herpes simplex virus from infected trigeminal ganglion to the murine cornea.herpes simplex virus type 1 (hsv) was introduced into the mouse trigeminal ganglion by stereotaxic injection. we examined the form in which the virus was transported anterograde within axons and the spread of virus to glial and endoneurial cells of the nerve using em immunocytochemistry. our results indicate that viral dissemination in the trigeminal nerve may occur both within the axon and in the extracellular space of the endoneurium. hsv is intraaxonally transported at least in part as a nucl ...200111311889
improving vaccine potency through intercellular spreading and enhanced mhc class i presentation of antigen.the potency of naked dna vaccines is limited by their inability to amplify and spread in vivo. vp22, a hsv-1 protein, has demonstrated the remarkable property of intercellular transport and may thus provide a unique approach for enhancing vaccine potency. therefore, we created a novel fusion of vp22 with a model ag, human papillomavirus type 16 e7, in a dna vaccine that generated enhanced spreading and mhc class i presentation of ag: these properties led to a dramatic increase in the number of e ...200111313416
eradication of murine brain tumors by direct inoculation of concentrated high titer-recombinant retrovirus harboring the herpes simplex virus thymidine kinase gene.implantation of retrovirus-producing cells within a tumor has been demonstrated to eliminate malignant brain tumors effectively in animal models. in our previous study, the implantation of high-titer retrovirus-producing fibroblasts into tumors resulted in highly efficient transduction in vivo. the transduced glioma cells migrated far from the implantation site, potentiating the induction of the remarkable bystander effect. it is also possible, however, that the implantation of murine fibroblast ...200111313793
combination suicide/cytokine gene therapy as adjuvants to a defective herpes simplex virus-based cancer vaccine.we have used syngeneic, established bilateral subcutaneous tumor models to examine the antitumor activity of herpes simplex virus (hsv) vectors, including the induction of an immune response against non-inoculated distant tumors. in such a model with ct26 murine colon adenocarcinoma, unilateral intratumoral inoculation of replication-deficient hsv-1 tsk inhibited the growth of both the inoculated and noninoculated established tumors. to enhance this limited antitumor immune response, we generate ...200111313808
vp22 enhanced intercellular trafficking of hsv thymidine kinase reduced the level of ganciclovir needed to cause suicide cell death.the inefficiency of herpes simplex virus thymidine kinase (tk) gene transfer and toxicity of ganciclovir (gcv) at high concentrations in vivo limits the use of this suicide gene therapy approach for the treatment of cancers in clinical settings. to overcome the problem, we have sought evidence of amplification of cytotoxicity by co-transfer of the tk gene fused with the gene encoding hsv-1 structural protein vp22 which has a remarkable ability for intercellular trafficking.200111318113
herpes simplex virus type 2 as a cause of acute retinal necrosis syndrome in young patients.to determine the causative virus in acute retinal necrosis (arn) syndrome in a series of patients by calculation of modified witmer coefficients.200111320015
herpes simplex virus encephalitis complicating myxedema coma treated with corticosteroids. 200111320194
[the effect of immunization with herpes simplex virus glycoprotein d fused with interluekin-2 against murine herpetic keratitis].to evaluate the effect of vaccination with fusion protein(gd-il-2) consisting of herpes simplex type1(hsv-1) glycoprotein d(gd) and human interleukin-2(il-2), and the effect of plasmid dna vaccine encoding gd-il-2 against murine herpetic keratitis.200111329945
epstein-barr virus-encoded protein kinase bglf4 mediates hyperphosphorylation of cellular elongation factor 1delta (ef-1delta): ef-1delta is universally modified by conserved protein kinases of herpesviruses in mammalian cells.translation elongation factor 1delta (ef-1delta) is hyperphosphorylated in various mammalian cells infected with alpha-, beta- and gammaherpesviruses and ef-1delta modification is mediated by viral protein kinases, including ul13 of herpes simplex virus type 1 and ul97 of human cytomegalovirus. in this study, the following is reported. (i) bglf4 encoded by the prototype gammaherpesvirus epstein-barr virus was purified as a fusion protein that was labelled with [gamma-(32)p]atp and labelling was ...200111369891
enhanced reporter gene expression in the rat brain from helper virus-free hsv-1 vectors packaged in the presence of specific mutated hsv-1 proteins that affect the virion.herpes simplex virus (hsv-1) gene expression is hypothesized to shut off promoters in hsv-1 vectors, but in a helper virus-free hsv-1 vector system, a number of promoters support only short-term expression. thus, recombinant gene expression remains short-term in the absence of approximately 99% of the hsv-1 genome. to resolve this paradox, we hypothesized that specific hsv-1 proteins that affect the virion can shut off recombinant gene expression. this study evaluated expression from hsv-1 vecto ...200111376851
preclinical safety evaluation of g207, a replication-competent herpes simplex virus type 1, inoculated intraprostatically in mice and nonhuman primates.g207, a replication-competent herpes simplex virus type 1 (hsv-1) virus, has been previously shown to be effective against human prostate cancer xenografts in mice. this study assesses its safety in the prostate of two animal models known for their sensitivity to hsv-1. balb/c mice were injected intraprostatically with either hsv-1 g207 or strain f and observed for 5 months. none of the g207-injected animals exhibited any clinical signs of disease or died. however, 50% of strain f-injected mice ...200111387063
icp0, icp4, or vp16 expressed from adenovirus vectors induces reactivation of latent herpes simplex virus type 1 in primary cultures of latently infected trigeminal ganglion cells.in a previous study, we demonstrated that infected-cell polypeptide 0 (icp0) is necessary for the efficient reactivation of herpes simplex virus type 1 (hsv-1) in primary cultures of latently infected trigeminal ganglion (tg) cells (w. p. halford and p. a. schaffer, j. virol. 75:3240-3249, 2001). the present study was undertaken to determine whether icp0 is sufficient to trigger hsv-1 reactivation in latently infected tg cells. to test this hypothesis, replication-defective adenovirus vectors th ...200111390616
differential incorporation of cd45, cd80 (b7-1), cd86 (b7-2), and major histocompatibility complex class i and ii molecules into human immunodeficiency virus type 1 virions and microvesicles: implications for viral pathogenesis and immune regulation.human immunodeficiency virus (hiv) infection results in a functional impairment of cd4(+) t cells long before a quantitative decline in circulating cd4(+) t cells is evident. the mechanism(s) responsible for this functional unresponsiveness and eventual depletion of cd4(+) t cells remains unclear. both direct effects of cytopathic infection of cd4(+) cells and indirect effects in which uninfected "bystander" cells are functionally compromised or killed have been implicated as contributing to the ...200111390619
design, synthesis and enzymatic activity of highly selective human mitochondrial thymidine kinase inhibitors.highly selective arabinofuranosyl nucleosides, which inhibit the mitochondrial thymidine kinase (tk-2) without affecting the closely related herpes simplex virus type 1 thymidine kinase (hsv-1 tk), varicella-zoster virus thymidine kinase (vzv-tk), cytosolic thymidine kinase (tk-1) or the multifunctional drosophila melanogaster deoxyribonucleoside kinase (dm-dnk), have been obtained. sar studies indicate a close relation between the length of the substituent at the 2' position of the arabinofuran ...200111392548
host selenium status selectively influences susceptibility to experimental viral myocarditis.the purpose of the present work was to determine whether dietary selenium (se) deficiency could influence the injurious effect of human viruses other than coxsackie virus b3 (cvb3) on mouse heart. weanling c3h/hen mice were fed a se-deficient or se-adequate diet for 4 wk and then were inoculated intraperitoneally with one of the following viruses: coxsackie virus b1 (cvb1), echovirus 9 (ev9), coxsackie virus a9 (cva9), or herpes simplex 1 (hsv1). polio virus 1 (pv1) was employed as a negative co ...200111393307
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
alphaherpesvirus proteins related to herpes simplex virus type 1 icp0 induce the formation of colocalizing, conjugated ubiquitin.herpes simplex virus type 1 immediate early protein icp0 influences virus infection by inducing the degradation of specific cellular proteins via a mechanism requiring its ring finger and the ubiquitin-proteasome pathway. many ring finger proteins, by virtue of their ring finger domain, interact with e2 ubiquitin-conjugating enzymes and act as a component of an e3 ubiquitin ligase. we have recently shown that icp0 induces the accumulation of colocalizing, conjugated ubiquitin, suggesting that ic ...200111333917
pcr-based plasmid vector construction for generation of recombinant viruses.a totally polymerase chain reaction (pcr)-based protocol for construction of plasmids for production of recombinant macropodid herpesvirus 1 (mahv-1) is described. this protocol greatly simplifies traditional methods that use restriction enzyme-based cloning or a combination of restriction enzyme cloning and the pcr. pcr is used to amplify the vector backbone containing an origin of replication and selectable marker, and the inserts to be cloned (5' and 3' viral homologous recombination regions ...200111337035
quantitative kinetics of [124i]fiau in cat and man.for the assessment of the efficacy of clinical gene therapy trials, different imaging modalities have been developed that enable a noninvasive assessment of location, magnitude, and duration of transduced gene expression in vivo. these imaging methods rely on a combination of an appropriate marker gene and a radiolabeled or paramagnetic marker substrate that can be detected by pet or mri. here, we assess whether the nucleoside analog 2'-fluoro-2'-deoxy-1beta-d-arabinofuranosyl-5-iodouracil (fiau ...200111337525
csf oligoclonal bands in ms include antibodies against chlamydophila antigens.considerable evidence suggests the role of an infectious agent in ms. the presence of chlamydophila pneumoniae in csf from patients with ms was shown earlier; to further examine this association the reactivity of the oligoclonal antibody response in the csf of patients with ms to c pneumoniae antigens was determined and compared with other antigens.200111342681
recurrent ocular herpes simplex keratitis following excimer laser photorefractive keratectomy in a rabbit model.reactivation of latent herpes simplex virus (hsv) by excimer laser photorefractive keratectomy(prk) has been reported previously in the literature. this study evaluates the extent of such hsv reactivation and determines whether corneal de-epithelialization prior to prk or the laser treatment itself induces this response.200111352456
a camp response element within the latency-associated transcript promoter of hsv-1 facilitates induced ocular reactivation in a mouse hyperthermia model.herpes simplex virus type 1 (hsv-1) recombinant strain 17cre contains a site-directed mutation in the 7-bp cre consensus sequence located 38 nucleotides upstream of the transcription start site. scarified mouse corneas received inoculations of 17syn+ (parent), 17cre, and rescue 17crer. slit lamp examination of herpetic lesions and tear film swabs containing infectious virus showed that 17cre had the same acute phenotype as 17syn+ and 17crer. at 4 weeks, when the corneas had healed and latency wa ...200111352668
oncolytic herpes simplex virus vector with enhanced mhc class i presentation and tumor cell killing.oncolytic herpes simplex virus type 1 (hsv-1) vectors are promising therapeutic agents for cancer. their efficacy depends on the extent of both intratumoral viral replication and induction of a host antitumor immune response. to enhance these properties while employing ample safeguards, two conditionally replicating hsv-1 vectors, termed g47delta and r47delta, have been constructed by deleting the alpha47 gene and the promoter region of us11 from gamma34.5-deficient hsv-1 vectors, g207 and r3616 ...200111353831
a novel, cell-specific attenuation of a herpes simplex virus type 1 infection in vivo.we have observed a cell-specific attenuation of herpes simplex virus type 1 strain 17syn+ in vivo that was dependent upon the cell type used to grow the virus. direct corneal infection of rabbits with 17syn+ propagated in vero cells caused 60% (6 of 10) to develop severe central nervous system (cns) disease as evidenced by seizures and/or paralysis; all neurologically impaired rabbits died. in contrast, infection of rabbits with 17syn+ propagated in bhk-21 cells induced seizures and was fatal in ...200111355305
analysis of protein expression from within the region encoding the 2.0-kilobase latency-associated transcript of herpes simplex virus type 1.during latent infections of sensory neurons, herpes simplex virus type 1 gene expression is restricted to the latency-associated transcripts (lats). the association of the stable 2.0-kb lat intron with polysomes has suggested that it might represent a novel mrna. in this work, we investigated expression of 2.0-kb lat open reading frames (orfs) by inserting the gene for green fluorescent protein (gfp) within the 2.0-kb lat sequence, both within a lat expression plasmid and in the context of the v ...200111238867
investigation of aciclovir-resistant herpes simplex virus i infection in a bone marrow transplantation unit: genotyping shows that different strains are involved.over an eight-month period from october 1997 to may 1998, four patients who had received a bone marrow transplant (bmt) from an unrelated donor presented with severe mucosal cutaneous infections involving aciclovir resistant herpes simplex virus 1 (hsv-1). the emergence within a short period of resistant hsv-1 strains in the bone marrow transplantation unit raised fears of hospital-acquired infections. the hypothesis was investigated by restriction fragment length polymorphism (rflp), sequencing ...200111247677
an initial atp-independent step in the unwinding of a herpes simplex virus type i origin of replication by a complex of the viral origin-binding protein and single-strand dna-binding protein.using a spectrophotometric assay that measures the hyperchromicity that accompanies the unwinding of a dna duplex, we have identified an atp-independent step in the unwinding of a herpes simplex virus type 1 (hsv-1) origin of replication, ori(s), by a complex of the hsv-1 origin binding protein (ul9 protein) and the hsv-1 single-strand dna binding protein (icp8). the sequence unwound is the 18-bp a + t-rich segment that links the two high-affinity ul9 protein binding sites, boxes i and ii of ori ...200111248025
herpes simplex virus dna packaging sequences adopt novel structures that are specifically recognized by a component of the cleavage and packaging machinery.the product of the herpes simplex virus type 1 u(l)28 gene is essential for cleavage of concatemeric viral dna into genome-length units and packaging of this dna into viral procapsids. to address the role of u(l)28 in this process, purified u(l)28 protein was assayed for the ability to recognize conserved herpesvirus dna packaging sequences. we report that dna fragments containing the pac1 dna packaging motif can be induced by heat treatment to adopt novel dna conformations that migrate faster t ...200111248036
a comparison of oral and parenteral routes for therapeutic vaccination with hsv-2 iscoms in mice; cytokine profiles, antibody responses and protection.it is likely that recurrent infections with hsv-2 (or hsv-1) are influenced by local levels of immunity at mucosal surfaces, when virus reactivated from the latent state is infecting mucosal epithelial cells. increasing the levels of cellular and humoral immunity through immunisation and maintaining such increased levels, may reduce establishment and spread of reactivated virus at the local site, thereby ameliorating recurrent disease symptoms. the use of hsv-2 antigens incorporated into immunos ...200111248361
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
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
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 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
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
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
mechanisms of replication of alpha- and betaherpesviruses and their pathogenesis.the diseases caused by herpes simplex virus (hsv) and human cytomegalovirus (cmv) differ and distinct differences in biological properties of these viruses can be noticed at laboratory work. despite of this, the structure of dna and the replication cycle of both viruses shows remarkably common features. analogous proteins encoded by both viruses, act at initiation of viral dna transcription, at viral dna synthesis, at nucleocapsid formation and envelopment. on other hand, considerable difference ...200111901707
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
the role of hsv in the transmission and progression of hiv.herpes simplex virus (hsv) is a common co-infection in persons infected with human immunodeficiency virus type 1 (hiv-1). chronic perianal ulceration from herpes simplex virus type 2 (hsv-2) was one of the first opportunisitc infections identified among patients with aids. subsequent research has established that the natural history of hsv-2 is altered in co-infected persons as they experience more frequent clinical and subclinical reactivation of hsv than persons infected only with hsv-2. in ad ...200111867018
the association of herpes simplex virus and alzheimer's disease: a potential synthesis of genetic and environmental factors.the chronic and sporadic nature of alzheimer's disease (ad), in which the majority of presenting cases are over 65 years of age, suggests that compounded injury or long-term exposure to environmental factors is involved in the aetiology, rather than inherited genetic alterations. great hope has been placed on identifying a causative infectious agent that would present the potential for therapeutic or preventative vaccines or drugs. although not the sole causative agent, herpes simplex virus type ...200111867022
in vitro activity of polyhydroxycarboxylates against herpesviruses and hiv.the antiviral activity of 17 polyhydroxycarboxylates derived from phenolic compounds was evaluated against herpesviruses and hiv. when present during virus adsorption several of the polymers exhibited potent activity against herpes simplex virus type 1 (hsv-1), hsv-2, thymidine kinase deficient hsv-1, human cytomegalovirus (hcmv) and hiv-1 and hiv-2 at concentrations that were not toxic to the host cells. a close correlation was found between the 50% inhibitory concentrations of the polyhydroxyc ...200112018678
[herpesviridae and laryngeal neoplasia].to investigate the relationship between herpesviridae and malignant or benign laryngeal diseases.200112541682
herpes simplex type i virus infection of cultured human vascular endothelial cells: expression of cell adhesion molecules and induction of interferon and cytokine production by blood mononuclear cells.the expression of cell adhesion molecules, p- and e-selectins, icam-1, and vcam-1, was studied in cultured human vascular endothelial cells (ecs) infected by herpes simplex type i virus (hsv-1). it was shown that ecs without any signs of the cytopathogenic effect (cpe) expressed on their surface p- and e-selectins as soon as 24 h after infection. no appearance of vcam-1 or increase in icam-1 expression was detected. peripheral blood mononuclear cells (pbmcs) isolated by gradient centrifugation a ...200112687235
neuronal apoptosis in herpes simplex virus - 1 encephalitis (hse).herpes simplex virus infections are encountered often due to their ubiquitous nature. common sites involved include skin, mucous membrane, genitalia, eye and the nervous system. hsv infection of the central nervous system can be life threatening. little is known about the pathogenesis of this cataclysmic disease, at the cellular level. virus induced apoptosis may play a role in the molecular pathogenesis of encephalitis. this study aims to detect the presence of apoptosis: a) in the brain tissue ...200117664814
overview of gene delivery into cells using hsv-1-based vectors.this overview describes the considerations involved in the preparation and use of herpes simplex virus type 1 (hsv-1) as a vector for gene transfer into neurons. strategies for gene delivery into neurons, either to study the molecular biology of brain function or for gene therapy, must utilize vectors that persist stably in postmitotic cells and that can be targeted both spatially and temporally in the nervous system in vivo. this unit describes the biology of hsv-1 along with a discussion cover ...200118428476
a novel and highly efficient production system for recombinant adeno-associated virus vector.recombinant adeno-associated virus (raav) has proven to be a promising gene delivery vector for human gene therapy. however, its application has been limited by difficulty in obtaining enough quantities of high-titer vector stocks. in this paper, a novel and highly efficient production system for raav is described. a recombinant herpes simplex virus type 1 (rhsv-1) designated hsv1-rc/deltaul2, which expressed adeno-associated virus type2 (aav-2) rep and cap proteins, was constructed previously. ...200218763068
effect of temperature, medium composition, and cell passage on production of herpes-based viral vectors.our work uses replication-defective genomic herpes simplex virus type-1 (hsv-1)-based vectors to transfer therapeutic genes into cells of the central nervous system and other tissues. obtaining highly purified high-titer vector stocks is one of the major obstacles remaining in the use of these vectors in gene therapy applications. we have examined the effects of temperature and media conditions on the half-life of hsv-1 vectors. the results reveal that hsv stability is 2.5-fold greater at 33 deg ...200217590937
viruses in the treatment of brain tumors.the grave outlook for malignant glioma patients in spite of improvements to current modalities has ushered in new approaches to therapy. viruses have emerged on the scene and gained attention for their ability to play essentially two roles: first, as vectors for therapeutic gene delivery and second, as engineered infectious agents capable of selectively lysing tumor cells. to date, clinical brain tumor trials using viruses for gene delivery have employed retroviral or adenoviral vectors to intro ...200212687911
transformation of human trabecular meshwork cells with sv40 tag alters promoter utilization.to compare promoter usage in primary differentiated and sv40 tag transformed human trabecular meshwork cells (htm and tm1 cells).200212789541
effects of long-term administration of cancer-promoting substances on oral subepithelial mast cells in the rat.the role of oral subepithelial mast cells in the defence against tumours is a matter of controversy. the effect of established and suggested carcinogens, such as the carcinogen 4-nitroquinoline-n-oxide (4-nqo) and herpes simplex virus type 1 (hsv-1), in combination with oral snuff on lower lip subepithelial mast cells (mc) was studied in rats. the rats were exposed to prolonged use of oral snuff. the test substances were administered in a surgically created canal in the lower lip of the rats. th ...200212529973
non-hiv antivirals - a review of the recent patent literature.this review covers the non-hiv antiviral patent literature from december 2001 to april 2002. most of the patent applications describe new compounds for the treatment of hepatitis c virus (hcv) by inhibition of the ns3 serine protease. several examples of both nucleoside and non-nucleoside inhibitors of the hcv polymerase ns5b have been reported. hepatitis b virus (hbv) therapy continues to be dominated by nucleoside analogs, but several non-nucleoside hbv polymerase inhibitors have also been rep ...200212802698
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