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different forms of hsv-1 vp22a within purified virion and infected cells.utilizing the monoclonal antibody mca406, our experimental data suggest that the herpes simplex virus type 1 (hsv-1) protein, vp22a, is present in the purified virus in a different form from that present within infected cells, namely the virion and infected-cell form, respectively. it seems reasonable to suggest that two different forms of vp22a are synthesized during the hsv-1 productive cycle. using varying quantities of reducing agents, both inter- and intramolecular disulfide linkages were d ...200011045375
potential role of famciclovir for prevention of herpetic whitlow in the health care setting.oral famciclovir was initiated in a health care worker immediately after an accidental percutaneous injury involving a needle freshly removed from a patient's herpes labialis vesicles. in follow-up, the health care worker remained seronegative for herpes simplex i and ii antibodies (igg and igm) and did not develop herpetic whitlow, supporting the potential role of famciclovir in the prevention of herpetic whitlow in a health care setting.200011049807
replication-competent herpes simplex viral vectors for cancer therapy. 200011050949
chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults : the cardiovascular health study.whether serological evidence of prior infection with chlamydia pneumoniae, herpes simplex virus type 1 (hsv-1), and cytomegalovirus (cmv) is associated with myocardial infarction (mi) and coronary heart disease (chd) death remains a source of controversy.200011067785
tegument-specific, virus-reactive cd4 t cells localize to the cornea in herpes simplex virus interstitial keratitis in humans.herpes stromal keratitis (hsk) is a prevalent and frequently vision-threatening disease associated with herpes simplex virus type 1 (hsv-1) infection. in mice, hsk progression occurs after viral clearance and requires t cells and neutrophils. one model implicates th1-like cd4 t cells with cross-reactivity between the hsv-1 protein ul6 and a corneal autoantigen. hsk can be prevented by establishing specific immunological tolerance. however, hsk can also occur in t-cell receptor-transgenic x scid ...200011069987
posttranslational processing of infected cell protein 22 mediated by viral protein kinases is sensitive to amino acid substitutions at distant sites and can be cell-type specific.infected cell protein 22 (icp22) is posttranslationally phosphorylated by the viral kinases encoded by u(s)3 and u(l)13 and nucleotidylylated by casein kinase ii. in rabbit and rodent cells and in primary human fibroblasts infected with mutants from which the alpha 22 gene encoding icp22 had been deleted, a subset of late (gamma(2)) gene products exemplified by u(l)38 and u(s)11 proteins are expressed at a reduced level, as measured by the accumulation of both mrna and protein. the same phenotyp ...200011070018
primary graft failure : a clinicopathologic and molecular analysis.primary graft failure (pgf) corneal tissues were analyzed for herpes simplex virus (hsv) and varicella-zoster virus (vzv).200011054337
replication of the herpes simplex virus type 1 rl1 mutant 1716 in primary neuronal cell cultures--possible relevance to use as a viral vector.the herpes simplex virus type 1 (hsv-1) rl1 deletion mutant 1716 has properties that make it a promising candidate as a viral vector for gene therapy in the human nervous system. these properties include its ability to spread along neural pathways and establish a latent infection in post-mitotic neurons, while retaining a non-virulent phenotype in vivo and an inability to cause a lytic infection in stationary or fully differentiated cells. in this study, we used viral replication assays and indi ...200011054493
in vitro and in vivo activity of eugenol on human herpesvirus.eugenol (4-allyl-1-hydroxy-2-methoxybenzene) was tested for antiviral activity against hsv-1 and hsv-2 viruses. in vitro, it was found that the replication of these viruses was inhibited in the presence of this compound. inhibitory concentration 50% values for the anti-hsv effects of eugenol were 25.6 microg/ml and 16.2 microg/ml for hsv-1 and hsv-2 respectively, 250 microg/ml being the maximum dose at which cytotoxicity was tested. eugenol was virucidal and showed no cytotoxicity at the concent ...200011054837
selective inhibition of herpes simplex virus type-1 uracil-dna glycosylase by designed substrate analogs.cytosine deamination and the misincorporation of 2'-durd into dna during replication result in the presence of uracil in dna. uracil-dna glycosylases (udgs) initiate the excision repair of this aberrant base by catalyzing the hydrolysis of the n-glycosidic bond. udgs are expressed by nearly all known organisms, including some viruses, in which the functional role of the udg protein remains unresolved. this issue could in principle be addressed by the availability of designed synthetic inhibitors ...200011084051
cloning of full length cdna, high-level expression and biological characterization of feline il-12.a full length cdna of feline interleukin(il)-12 p35 and p40 subunits was cloned. by transferring the plasmids containing both the subunit genes to mammalian cells, we expressed biologically active feline il-12. the expressed feline il-12 has interferon-gamma-inducing activity against both human and feline peripheral blood mononuclear cells (pbmc) and stimulates cytotoxic t lymphocyte activity against herpes simplex virus-infected human pbmcs. there were two kinds of molecules (p75, p80) in the p ...200011073079
a null mutation in the ul36 gene of herpes simplex virus type 1 results in accumulation of unenveloped dna-filled capsids in the cytoplasm of infected cells.the ul36 open reading frame (orf) encodes the largest herpes simplex virus type 1 (hsv-1) protein, a 270-kda polypeptide designated vp1/2, which is also a component of the virion tegument. a null mutation was generated in the ul36 gene to elucidate its role in the virus life cycle. since the ul36 gene specifies an essential function, complementing cell lines transformed for sequences encoding the ul36 orf were made. a mutant virus, designated kdeltaul36, that encodes a null mutation in the ul36 ...200011090159
mutations in herpes simplex virus glycoprotein d distinguish entry of free virus from cell-cell spread.herpes simplex virus type 1 (hsv-1) glycoprotein d (gd) is an essential component of the entry apparatus that is responsible for viral penetration and subsequent cell-cell spread. to test the hypothesis that gd may serve distinguishable functions in entry of free virus and cell-cell spread, mutants were selected for growth on u(s)11cl19.3 cells, which are resistant to both processes due to the lack of a functional gd receptor, and then tested for their ability to enter as free virus and to sprea ...200011090139
interaction of the herpes simplex virus type 1 packaging protein ul15 with full-length and deleted forms of the ul28 protein.the ul15 and ul28 proteins of herpes simplex virus type 1 are both required for the packaging of replicated viral dna into the viral capsid. we have expressed ul28 and a functional epitope-tagged form of ul15 in mammalian and insect cells. immunoprecipitation experiments confirmed that the two proteins can interact. in agreement with previous results, ul15, when expressed alone, entered the nucleus but ul28 remained cytoplasmic. when co-expressed the two proteins co-localized in the nucleus. six ...200011086131
comparison of several elisa tests for detecting the presence of igg and igm against herpes simplex viruses.four enzyme-linked immunosorbent assays designated test 1 (eti-hsvk-g 1/2); test 2 (eti-hsvk-m 1/2); test 3 (eti-hsvk-g 2), and test 4 (bioelisa hsv2 igg) were studied to evaluate different stages of herpes simplex virus (hsv) infection. samples (50 sera and 14 cerebrospinal fluid) were included in four groups. group 1 consisted of samples from patients with primary hsv infections; group 2 comprised samples from patients with recurrent hsv infections; group 3 were samples nonreactive to hsv; and ...200011092194
[immunogenic activity of temperature sensitive mutation of herpes simplex virus type-1 in mono- and polyvalent conditions with different attenuated strains of virus. ii. analysis of humoral immunologic response induced by mutants of temperature sensitive herpes simplex type-1 virus in polyvalent systems].the ability of mutant ts hsv-1 on 45 passage to induction of igg antibody response in the presence of other attenuated viral strain, like measles, mumps, rubella was evaluated, and the effect of mutant ts hsv-1 on humoral immunity induced by attenuated measles and mumps strains was also tested. the obtained results clearly indicated that even immunization with other rna virus strains had no effect on igg antibody response to mutant ts hsv-1. significant differences were observed in igg antibody ...200011107783
current diagnostic techniques in genital herpes: their role in controlling the epidemic.genital herpes continues to be a public health problem in both developed and developing countries. laboratory confirmation of clinical diagnosis is important, particularly as there are other conditions which present similarly to genital herpes, while atypical presentations of genital herpes also occur. herpes simplex virus type 2 (hsv-2) is the most common cause of genital herpes globally, although hsv-1 genital herpes infections occur also. type-specific serology has overcome the technical prob ...200011109508
what triggers recurrences of herpes simplex keratitis. 200011115264
impaired induction of protective immunity by highly virulent herpes simplex virus type 2 in a murine model of genital herpes.we investigated the immune events in the vagina of mice intravaginally infected with highly virulent herpes simplex virus type 2 (hsv-2) strain 186, and compared them with those induced by hsv type 1 strain kos, a widely known laboratory strain. although there was no significant difference between 186 and kos in the viral replication in the initial stage of infection, inadequate and delayed clearance of virus from the vaginal mucosa was observed in 1 86-challenged mice. the induction of antigen- ...200011087087
a phase iii clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme.previous uncontrolled clinical trials have shown the in vivo retrovirus (rv)-mediated transduction of glioblastoma cells with the herpes simplex virus thymidine kinase (hsv-tk) gene and subsequent systemic treatment with ganciclovir to be feasible and well tolerated. however, because of continued tumor progression in most patients, the antitumor effect could not be determined using historical controls. here, we describe a phase iii, multicenter, randomized, open-label, parallel-group, controlled ...200011096443
effects of preexisting immunity on the response to herpes simplex-based oncolytic viral therapy.herpes simplex viruses (hsv) type 1 are the basis of a number of anticancer strategies that have proven efficacious in animal models. they are natural human pathogens and the majority of adults have anti-hsv immunity. the current study examined the effect of preexisting immunity on the response to herpes-based oncolytic viral treatment of hepatic metastatic cancer in a murine model designed to simulate a clinical approach likely to be utilized for nonneurological tumors. specifically, the antica ...200011119418
oncolytic viral therapy for human prostate cancer by conditionally replicating herpes simplex virus 1 vector g207.over the last few years, a conditionally replicating herpes simplex virus 1 (hsv-1) vector, g207 has been used for the treatment of several malignant tumors. in this article we evaluate the anti-tumoral effect of g207 against prostate cancer in vitro and in vivo. the susceptibility of the human prostate cancer cell lines, du145 and pc3 to g207 at a multiplicity of infection (moi) of 0.1 was examined. in addition, the growth characteristics of g207 were assessed. athymic mice with s.c. tumors wer ...200011123435
[alternative diagnoses among suspected herpes simplex encephalitis patients with negative polymerase chain reaction].the aim of this study was to analyze the diagnosis found in a series of patients in which the diagnosis of herpes simplex encephalitis (hse) was ruled out by a negative polymerase chain reaction (pcr) result for hsv dna in cerebrospinal fluid (csf) samples. forty three out of 61 hse suspected patients had negative pcr. an alternative diagnosis was established in 41.9% of these patients. these patients were diagnosed as having viral (2 cases-11.1%) and non viral (5 cases-27.2%) cns infections, va ...200011105075
is it safe to reuse disposable laparoscopic trocars? an in vitro testing.the reuse of disposable laparoscopic instruments carries a risk of transmitting infectious diseases such as hepatitis and hiv. we evaluated the safety of reusing disposable trocars by studying the chances of their harboring infectious viruses after resterilization in an in vitro setting.200011116415
the protective effect of hochu-ekki-to (tj-41), a japanese herbal medicine, against hsv-1 infection in mitomycin c-treated mice.immmunosuppression and infectious disease in cancer patients receiving chemotherapy is a serious problem. immunopotentiating drugs may show a therapeutic efficacy.200011131680
increased severity of hsv-1 keratitis and mortality in mice lacking the 2-5a-dependent rnase l gene.the2',5'-oligoadenylate-dependent rnase l gene functions in the interferon-inducible rna decay pathway known as the 2-5a system. the purpose of this study was to determine whether the absence of this gene affects the pathogenesis of herpes simplex virus type 1 (hsv-1) ocular infection in the mouse.200111133856
transcutaneous immunisation with herpes simplex virus stimulates immunity in mice.herpes simplex virus (hsv) is common throughout the world and is a target for vaccine development. transcutaneous immunisation is a novel technique that uses the application of vaccine antigens in solution on the skin in the presence of cholera toxin (ct) as an adjuvant. this study investigated the potential of transcutaneous immunisation in c3h mice, using ct co-administered with whole inactivated hsv-1 (ct+hsvi) or hsv-1 antigens extracted from infected vero cells (ct+hsvag) or a control prote ...200011118905
t-cell suicide gene therapy for organ transplantation: induction of long-lasting tolerance to allogeneic heart without generalized immunosuppression.standard immunosuppressive drugs used for allogeneic organ transplantation do not specifically target alloreactive t cells and must be given for the lifetime of the patient, resulting in significant morbidity and mortality. we aimed to induce experimental immune tolerance to vascularized heart allograft using a suicide gene allowing selective elimination of dividing t cells expressing herpes simplex virus type 1 thymidine kinase upon ganciclovir administration. we show that without ganciclovir, ...200011124060
efficient suicide gene therapy of transduced and distant untransduced ovary tumors is correlated with significant increase of intratumoral t and nk cells.gene therapy using herpes simplex type 1 thymidine kinase gene (hsv1-tk) transfer followed by ganciclovir (gcv) treatment has revealed an important intratumoral and regional bystander effect that is at least partly immune-mediated. the aim of this work was to study the modifications of t lymphocyte subpopulations in a model of distant bystander effect occurring between ovary tumors. bilateral ovarian tumors were generated in 21 wky rats by injection in the ovarian pouch of either parental or hsv ...200011130846
herpes simplex virus ge/gi sorts nascent virions to epithelial cell junctions, promoting virus spread.alphaherpesviruses spread rapidly through dermal tissues and within synaptically connected neuronal circuitry. spread of virus particles in epithelial tissues involves movement across cell junctions. herpes simplex virus (hsv), varicella-zoster virus (vzv), and pseudorabies virus (prv) all utilize a complex of two glycoproteins, ge and gi, to move from cell to cell. hsv ge/gi appears to function primarily, if not exclusively, in polarized cells such as epithelial cells and neurons and not in non ...200111134295
accumulation of herpes simplex virus type 1 early and leaky-late proteins correlates with apoptosis prevention in infected human hep-2 cells.we previously reported that a recombinant icp27-null virus stimulated, but did not prevent, apoptosis in human hep-2 cells during infection (m. aubert and j. a. blaho, j. virol. 73:2803-2813, 1999). in the present study, we used a panel of 15 recombinant icp27 mutant viruses to determine which features of herpes simplex virus type 1 (hsv-1) replication are required for the apoptosis-inhibitory activity. each virus was defined experimentally as either apoptotic, partially apoptotic, or nonapoptot ...200111134315
lymphotoxin alpha-/- mice develop functionally impaired cd8+ t cell responses and fail to contain virus infection of the central nervous system.recent observations have indicated that viral persistence and tumor spreading could occur because of effector function-defective cd8(+) t cells. although chronic exposure to ag, lack of cd4 help, and epitope dominance are suggested to interfere with ctl differentiation, mechanisms underlying the defective effector function remain obscure. we demonstrate in this report that lymphotoxin alpha-deficient mice develop cd8(+) t cells at normal frequencies when infected with hsv or immunized with ova a ...200111145686
interactions of herpes simplex virus type 1 with nd10 and recruitment of pml to replication compartments.many of the events required for productive herpes simplex virus type 1 (hsv-1) infection occur within globular nuclear domains called replication compartments, whose formation appears to depend on interactions with cellular nuclear domains 10 (nd10). we have previously demonstrated that the formation of hsv-1 replication compartments involves progression through several stages, including the disruption of intact nd10 (stage i to stage ii) and the formation of pml-associated prereplicative sites ...200111160739
epstein-barr virus immediate-early protein bzlf1 is sumo-1 modified and disrupts promyelocytic leukemia bodies.although the immediate-early proteins of both herpes simplex virus (hsv) and cytomegalovirus (cmv) are known to modify promyelocytic leukemia (pml) (nd10) bodies in the nucleus of the host cell, it has been unclear whether lytic infection with gamma herpesviruses induces a similar effect. the pml protein is induced by interferon, involved in major histocompatibility complex class i presentation, and necessary for certain types of apoptosis. therefore, it is likely that pml bodies function in an ...200111160742
mutation of gln125 to asn selectively abolishes the thymidylate kinase activity of herpes simplex virus type 1 thymidine kinase.the broad substrate specificity of herpes simplex virus type 1 (hsv-1) thymidine kinase (tk) has provided the basis for selective antiherpetic therapy and, more recently, suicide gene therapy for the treatment of cancer. we have now constructed an hsv-1 tk mutant enzyme, in which an asparagine (n) residue is substituted for glutamine (q) at position 125, and have evaluated the effect of this amino acid change on enzymatic activity. in marked contrast with wild-type hsv-1 tk, which displays both ...200111160865
herpesvirus-mediated systemic delivery of nerve growth factor.sustained systemic dissemination of therapeutic proteins from peripheral sites is an attractive prospect for gene therapy applications. replication-defective genomic herpes simplex virus type 1 (hsv-1) vectors were evaluated for their ability to express nerve growth factor (ngf) as a model gene product both locally and systemically. intra-articular inoculation of ngf expression vectors in rabbits resulted in significant increases in joint lavage and blood plasma ngf that persisted for 1 year. a ...200111162312
cerebellar projections to the prefrontal cortex of the primate.the cerebellum is known to project via the thalamus to multiple motor areas of the cerebral cortex. in this study, we examined the extent and anatomical organization of cerebellar input to multiple regions of prefrontal cortex. we first used conventional retrograde tracers to map the origin of thalamic projections to five prefrontal regions: medial area 9 (9m), lateral area 9 (9l), dorsal area 46 (46d), ventral area 46, and lateral area 12. only areas 46d, 9m, and 9l received substantial input f ...200111160449
protective mucosal immunity to ocular herpes simplex virus type 1 infection in mice by using escherichia coli heat-labile enterotoxin b subunit as an adjuvant.the potential of nontoxic recombinant b subunits of cholera toxin (rctxb) and its close relative escherichia coli heat-labile enterotoxin (retxb) to act as mucosal adjuvants for intranasal immunization with herpes simplex virus type 1 (hsv-1) glycoproteins was assessed. doses of 10 microg of retxb or above with 10 microg of hsv-1 glycoproteins elicited high serum and mucosal anti-hsv-1 titers comparable with that obtained using ctxb (10 microg) with a trace (0.5 microg) of whole toxin (ctx-ctxb) ...200111160664
the zinc ring finger in the bicp0 protein encoded by bovine herpesvirus-1 mediates toxicity and activates productive infection.the bicp0 protein encoded by bovine herpesvirus 1 (bhv-1) is believed to activate transcription and consequently productive infection. expression of full-length bicp0 protein is toxic in transiently transfected mouse neuroblastoma cells (neuro-2a) in the absence of other viral genes. however, bicp0 does not appear to directly induce apoptosis. although bicp0 is believed to be functionally similar to the herpes simplex virus type 1-encoded icp0, the only protein domain that is well conserved is a ...200111172088
characterization of herpes simplex viruses selected in culture for resistance to penciclovir or acyclovir.penciclovir (pcv), an antiherpesvirus agent in the same class as acyclovir (acv), is phosphorylated in herpes simplex virus (hsv)-infected cells by the viral thymidine kinase (tk). resistance to acv has been mapped to mutations within either the tk or the dna polymerase gene. an identical activation pathway, the similarity in mode of action, and the invariant cross-resistance of tk-negative mutants argue that the mechanisms of resistance to pcv and acv are likely to be analogous. a total of 48 h ...200111160674
the three hvea receptor ligands, gd, lt-alpha and light bind to distinct sites on hvea.the herpes virus entry mediator a (hvea), a member of the tumor necrosis factor receptor (tnfr) superfamily, interacts with three different protein ligands; lymphotoxin-alpha (lt-alpha) and light (light stands for lymphotoxin homolog, which exhibits inducible expression and competes with hsv glycoprotein d for hvea and is expressed on t-lymphocytes) from the host and the herpes simplex virus (hsv) surface glycoprotein gd. it has been reported that the gd binding site on hvea is located within th ...200011164894
autocrine action of il-10 suppresses proinflammatory mediators and inflammation in the hsv-1-infected cornea.we investigated whether il-10 produced endogenously would influence the development of hsv-1-induced acute corneal disease. murine corneal epithelial cells and fibroblasts cultured in vitro expressed il-10 mrna and protein constitutively and also il-10 receptors. inclusion of il-10 neutralizing antibody in the culture medium significantly (p<0.05) enhanced tnf-alpha-induced il-6 and mip-2 production by both corneal cell types. endogenous il-10 synthesis, which also occurred in vivo, was not modu ...200111200059
effects of structural modification of calcium spirulan, a sulfated polysaccharide from spirulina platensis, on antiviral activity.calcium ion binding with the anionic part of a molecule was replaced with various metal cations and their inhibitory effects on the replication of herpes simplex virus type 1 were evaluated. replacement of calcium ion with sodium and potassium ions maintained the antiviral activity while divalent and trivalent metal cations reduced the activity. depolymerization of sodium spirulan with hydrogen peroxide decreased in antiviral activity as its molecular weight decreased.200111201213
characterisation of ie and ul5 gene products of equine herpesvirus 1 using dna inoculation of mice.the equine herpesvirus 1 (ehv-1) strain hvs25a regulatory genes ie and ul5, encoding homologues of herpes simplex virus 1 (hsv-1) icp4 and icp27 respectively, were cloned into a eukaryotic expression vector and the dna injected intramuscularly into mice. antibodies produced in this way detected the ie or ul5 gene products as diffuse material in nuclei of rk13 cells transfected with the individual genes but as discrete punctate or large aggregates in rk13 cells infected with ehv-1. western blotti ...200011205113
induction of arginases i and ii in cornea during herpes simplex virus infection.induction of inducible nitric oxide synthase (inos) following corneal infection with herpes simplex virus type-1 (hsv-1) generates nitric oxide (no), an important player in the defense against viral infection. changes in arginine metabolism during infection are not limited to effects of inos but can also involve arginases, which can modulate no synthesis and produce ornithine for the generation of polyamines and proline. the latter are important molecules involved in tissue damage and repair dur ...200111172921
8-[18f]fluoropenciclovir: an improved reporter probe for imaging hsv1-tk reporter gene expression in vivo using pet.we have synthesized and evaluated 8-[18f]fluoropenciclovir (fpcv) and compared it with 8-[18f]fluoroganciclovir (fgcv) for monitoring the expression of herpes simplex virus type 1 thymidine kinase (hsv1 -tk) reporter gene in cell culture and in vivo.200111197989
nuclear localization and shuttling of herpes simplex virus tegument protein vp13/14.the herpes simplex virus type 1 gene ul47 encodes the tegument proteins referred to collectively as vp13/14, which are believed to be differentially modified forms of the same protein. here we show that the major product of the ul47 gene during transient expression is vp14, suggesting that some feature of virus infection is required to produce vp13. we have tagged vp13/14 with green fluorescent protein and have demonstrated that the protein is targeted efficiently to the nucleus, where it often ...200111222679
fluorescent tagging of herpes simplex virus tegument protein vp13/14 in virus infection.the cellular site of herpesvirus tegument assembly has yet to be defined. we have previously used a recombinant herpes simplex virus type 1 expressing a green fluorescent protein (gfp)-tagged tegument protein, namely vp22, to show that vp22 is localized exclusively to the cytoplasm during infection. here we have constructed a similar virus expressing another fluorescent tegument protein, yfp-vp13/14, and have visualized the intracellular localization of this second tegument protein in live infec ...200111222680
modified fgf4 signal peptide inhibits entry of herpes simplex virus type 1.entry of herpes simplex virus type 1 (hsv-1) into host cells occurs through fusion of the viral envelope with the plasma membrane and involves complex and poorly understood interactions between several viral and cellular proteins. one strategy for dissecting the function of this fusion machine is through the use of specific inhibitors. we identified a peptide with antiviral activity that blocks hsv-1 infection at the entry stage and during cell-to-cell spreading. this peptide (called eb for "ent ...200111222686
interaction of hsv-1 infected peripheral blood mononuclear cells with cultured dermal microvascular endothelial cells: a potential model for the pathogenesis of hsv-1 induced erythema multiforme.the effect of herpes virus infection on human dermal microvascular endothelial cells and herpes-virus-1-infected peripheral blood mononuclear cells on human dermal microvascular endothelial cells was studied as a model of herpes-associated erythema multiforme. after infection of human dermal microvascular endothelial cells with native herpes virus and overnight culture, 60%--90% of human dermal microvascular endothelial cells showed cytopathic effects. hla class i molecules and cd31 (pecam-1) su ...200111168811
comparison of four enzyme immunoassays with a western blot assay for the determination of type-specific antibodies to herpes simplex virus.most current enzyme immunoassays (eias) differentiate inadequately between types 1 and 2 herpes simplex virus (hsv) antibodies since significant cross-reactivity exists. we compared 4 igg type-specific eias using a western blot assay for resolution of discrepant results. the diamedix had sensitivities of 100% for types 1 and 2 but specificities of only 71% and 61%, respectively. the cross-reactivity rate was 82% in positive samples tested. for hsv types 1 and 2, the zeus sensitivities were 92% a ...200111211617
inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide.despite advances in antiviral chemotherapy, herpes simplex virus type 1 (hsv-1), continues to complicate the clinical course of many allograft recipients. we have previously demonstrated that the experimental immunosuppressive agent leflunomide inhibits production of cytomegalovirus by interference with virion assembly. we test the hypothesis that this agent exerts similar antiviral activity against hsv-1.200111211189
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
the relationship between spontaneous telomere loss and chromosome instability in a human tumor cell line.chromosome instability plays an important role in cancer by promoting the alterations in the genome required for tumor cell progression. the loss of telomeres that protect the ends of chromosomes and prevent chromosome fusion has been proposed as one mechanism for chromosome instability in cancer cells, however, there is little direct evidence to support this hypothesis. to investigate the relationship between spontaneous telomere loss and chromosome instability in human cancer cells, clones of ...200011228547
a simple procedure for expression and purification of selected non-structural (alpha and beta) herpes simplex virus 1 (hsv-1) proteins.the expression and isolation of herpes simplex virus 1 (hsv-1) immediate early (alpha) ie63 (icp27) and of the early (beta) thymidine kinase (tk) polypeptides in escherichia coli jm 109 cells transformed with the pinpoint xa-1 (promega) plasmid construct carrying either the hsv-1 ul54 or ul23 genes are described. the resulting biotinylated fusion protein(s) could be easily induced and were purified in appropriate amounts by means of a monomeric avidin-conjugated resin (softlink soft release avid ...200111226559
combined suicide and granulocyte-macrophage colony-stimulating factor gene therapy induces complete tumor regression and generates antitumor immunity.the use of prodrug-activated ("suicide") gene therapy has been shown to be effective in inducing tumor regression when only a small proportion of tumor cells contains the suicide gene. these experiments were designed to test whether additional therapeutic benefit may be obtained by stimulating the immune response. murine mc26 colon carcinoma cells, either untransduced or transduced with genes for herpes simplex virus-1 thymidine kinase (hsv1-tk) or human gm-csf, were injected subcutaneously into ...200011228530
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
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
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
molecular mechanisms of replication of herpes simplex virus 1.the present review focuses on recent development in our understanding of the molecular mechanisms of dna replication of herpes simplex virus 1 (hsv-1). progress made in the characterization of the early events of viral dna synthesis and of virus-host cell interactions, especially in the context with the formation of viral dna replication sites, is highlighted. an up-dated overview is presented on important stages of lytic infection cycle, such as virion entry, viral dna synthesis, viral dna clea ...200011252674
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
modest increases in the titers of helper virus-free herpes simplex virus 1 (hsv-1) vectors by packaging in a cell line with inducible expression of hsv-1 vp16 or by treatment with n,n'-hexamethylene-bis-acetamide.a recently developed helper virus-free hsv-1 vector system has potential for both gene therapy and physiological studies, but relatively low vector titers have complicated use of this system. in this report, we explored improving the vector titers by isolating a vero cell line that uses the tetracycline-regulated promoter system to induce hsv-1 vp16 at the beginning of the packaging procedure. we isolated the required cell line and demonstrated that it supports enhanced expression from a hsv-1 i ...200011332280
[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
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
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
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
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
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
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
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
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
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
aquamune, a brown seaweed extract, improves metabolism, immune response, energy and chelates heavy metals.the national cancer institute (nci) has shown interest in the curative powers of ocean plants, many of which appear to possess powerful anti-inflammatory, antiviral, antimicrobial, antifungal, anticancer, and immuno-suppressive properties. aquamune, a brown seaweed extract developed by aqua-10 laboratories, has gained marketing rights for use as a nutritional supplement. research shows that it acts as a receptor blocker for many pathogens, including salmonella, and is effective against haemophil ...199811365014
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
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
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
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
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