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identification and initial characterization of four novel members of the interleukin-1 family.interleukin-1 (il-1), fibroblast growth factors (fgfs), and their homologues are secreted factors that share a common beta-barrel structure and act on target cells by binding to cell surface receptors with immunoglobulin-like folds in their extracellular domain. while numerous members of the fgf family have been discovered, the il-1 family has remained small and outnumbered by il-1 receptor homologues. from expressed sequence tag data base searches, we have now identified four additional il-1 ho ...200010744718
conservative mutations of glutamine-125 in herpes simplex virus type 1 thymidine kinase result in a ganciclovir kinase with minimal deoxypyrimidine kinase activities.the herpes simplex virus type 1 thymidine kinase (hsv-1 tk) is the major anti-herpes virus pharmacological target, and it is being utilized in combination with the prodrug ganciclovir as a toxin gene therapeutic for cancer. one active-site amino acid, glutamine-125 (gln-125), has been shown to form hydrogen bonds with bound thymidine, thymidylate, and ganciclovir in multiple x-ray crystal structures. to examine the role of gln-125 in hsv-1 tk activity, three site-specific mutations of this resid ...200010747801
conditionally replicating herpes vectors for cancer therapy. 200010749560
cross-reactive antibodies against gm2 and cmv-infected fibroblasts in guillain-barré syndrome.to investigate whether anti-gm2 antibodies in patients with guillain-barré syndrome (gbs) are induced by molecular mimicry with cytomegalovirus (cmv).200010751257
isolation of herpes simplex virus procapsids from cells infected with a protease-deficient mutant virus.herpes simplex virus type 1 (hsv-1) capsid proteins assemble in vitro into spherical procapsids that differ markedly in structure and stability from mature polyhedral capsids but can be converted to the mature form. circumstantial evidence suggests that assembly in vivo follows a similar pathway of procapsid assembly and maturation, a pathway that resembles those of double-stranded dna bacteriophages. we have confirmed the above pathway by isolating procapsids from hsv-1-infected cells and chara ...200010644336
anterograde transport of herpes simplex virus type 1 in cultured, dissociated human and rat dorsal root ganglion neurons.the mechanism of anterograde transport of herpes simplex virus was studied in cultured dissociated human and rat dorsal root ganglion neurons. the neurons were infected with hsv-1 to examine the distribution of capsid (vp5), tegument (vp16), and glycoproteins (gc and gb) at 2, 6, 10, 13, 17, and 24 h postinfection (p.i.) with or without nocodazole (a microtubule depolymerizer) or brefeldin a (a golgi inhibitor). retrogradely transported vp5 was detected in the cytoplasm of the cell body up to th ...200010644356
synthesis and antiviral activity of novel anti-vzv 5-substituted uracil nucleosides with a cyclopropane sugar moiety.a series of 5-substituted uracil nucleoside derivatives with a 1(1's, 2'r)-[1',2'-bis(hydroxymethyl)cyclopropyl]methyl group as an acyclosugar moiety were synthesized and evaluated for their anti-herpetic activities. among the compounds synthesized, (e)-5-halovinyluracil derivatives showed superior anti-varicella zoster virus (vzv) activity over acyclovir (acv) but were less potent than acv against herpes symplex virus type-1 (hsv-1). ic(50) values for the vzv kawaguchi strain were 0.027 for br, ...200010649983
simulfluor respiratory screen for rapid detection of multiple respiratory viruses in clinical specimens by immunofluorescence staining.a new rapid direct immunofluorescence assay (dfa) respiratory screen reagent for detection of seven common respiratory viruses (respiratory syncytial virus [rsv], influenza a and b viruses, parainfluenza virus types 1 to 3, and adenovirus) was compared with standard single or dual dfa reagents and culture. in total, 1,531 respiratory samples were adequate for testing with both simulfluor respiratory screen (rs) reagent (chemicon international, temecula, calif.) and single or dual dfa reagents. t ...200010655371
rapid discrimination of monkey b virus from human herpes simplex viruses by pcr in the presence of betaine.a pcr method to amplify dna segments of the glycoprotein g gene of monkey b virus (bv) was achieved by adding betaine to the pcr mixture, in spite of the high g+c content of this gene. no product was obtained when dna of human herpes simplex viruses (hsvs) was used as the template under the same conditions. thus, this pcr method is useful in discriminating bv from hsvs.200010699035
[herpes simplex virus type 1 and 2 in switzerland].a worldwide increase in the incidence of genital herpes infections has been described in recent years. transmission of the herpes simplex virus type 2 (hsv-2) by asymptomatic seropositive subjects is considered to be a relevant mode of infection. the seroprevalence of hsv-2 varies considerably between different populations. in europe, data are scarce and the epidemiological situation in switzerland is unknown. in 1997 we performed serological examinations in 151 adult volunteers (87% between 20 ...200010701231
the u box is a modified ring finger - a common domain in ubiquitination. 200010704423
necrotizing ulcerative stomatitis in human immunodeficiency virus-seropositive individuals: a review of the histopathologic, immunohistochemical, and virologic characteristics of 18 cases.the purpose of this retrospective study was to delineate the histopathologic, immunohistochemical, and virologic characteristics of 18 cases of necrotizing ulcerative stomatitis.200010710458
postherpetic lacrimal obstruction.the purpose of the study was to review the surgical management of postherpetic lacrimal obstruction.200010711887
cytogenetic genotoxicity of anti-herpes purine nucleoside analogues in cho cells expressing the thymidine kinase gene of herpes simplex virus type 1: comparison of ganciclovir, penciclovir and aciclovir.the three anti-herpes nucleoside analogues ganciclovir, penciclovir and aciclovir were investigated as to their recombinogenic [sister chromatid exchange (sce) inducing] and clastogenic activity in cho cells expressing the thymidine kinase gene of hsv-1, which is a precondition of therapeutic activity of these drugs. the compounds were applied for the duration of one cell cycle and cytogenetic end-points were measured between 0 and 42 h after exposure. although the nucleoside analogues are quite ...200010719044
coronavirus-induced membrane fusion requires the cysteine-rich domain in the spike protein.the spike glycoprotein of mouse hepatitis virus strain a59 mediates the early events leading to infection of cells, including fusion of the viral and cellular membranes. the spike is a type i membrane glycoprotein that possesses a conserved transmembrane anchor and an unusual cysteine-rich (cys) domain that bridges the putative junction of the anchor and the cytoplasmic tail. in this study, we examined the role of these carboxyl-terminal domains in spike-mediated membrane fusion. we show that th ...200010725213
acremonium keratitis in a patient with herpetic neurotrophic corneal disease.fungi belonging to the genus acremonium link ex fries 1821 are ubiquitous environmental contaminants and soil saprophytes, but are infrequent pathogens in humans. these filamentous fungi (previously known as cephalosporium) are an uncommon cause of mycotic keratitis. as in the case of other filamentous fungi, corneal trauma with contaminated matter is the most frequent risk factor for the infection. we report in this paper a case of keratomycosis caused by acremoniumpotronii, in a patient with a ...200010726803
herpes simplex virus virion host shutoff (vhs) activity alters periocular disease in mice.during lytic infection, the virion host shutoff (vhs) protein of herpes simplex virus (hsv) mediates the rapid degradation of rna and shutoff of host protein synthesis. in mice, hsv type 1 (hsv-1) mutants lacking vhs activity are profoundly attenuated. hsv-2 has significantly higher vhs activity than hsv-1, eliciting a faster and more complete shutoff. to examine further the role of vhs activity in pathogenesis, we generated an intertypic recombinant virus (kosv2) in which the vhs open reading f ...200010729135
herpes simplex virus type 1 as a cause of widespread intracorneal blistering of the lower limbs.herpes simplex virus (hsv) infections often manifest as acute self-limiting eruptions of grouped vesicles, which have a tendency to recur. common manifestations include that of gingivostomatitis, vulvovaginitis, recurrent erythema multiforme, herpetic whitlow, and eczema herpeticum. we report a case of hsv-1 presenting as a symmetrical intracorneal blistering eruption involving the lower limbs in a patient with no previous history of herpes simplex infection.200010733634
polyherbal formulations with wide spectrum antimicrobial activity against reproductive tract infections and sexually transmitted pathogens.recent reports indicate high incidence of genital infections, most of which are sexually transmitted. although specific drugs and antibiotics are available for some, a safe spermicidal formulation with wide spectrum antimicrobial action would be a desirable addition to the presently available spermicides.200010735590
two leaky-late hsv-1 promoters differ significantly in structural architecture.the hsv-1 vp5 and vp16 transcripts are expressed with leaky-late (gamma1) kinetics and reach maximal levels after viral dna replication. while the minimal vp5 promoter includes only an sp1 site at -48, a tata box at -30, and an initiator (inr) element at the cap site, here we show that elements upstream of -48 can functionally compensate for the mutational loss of the critical sp1 site at -48. to determine whether this is a general feature of leaky-late promoters, we have carried out a detailed ...200010873762
purification and characterization of of-1, a host factor implicated in herpes simplex replication.a human cellular factor (of-1) has been previously implicated in replication of herpes simplex virus, type 1. this protein binds to three conserved regions (boxes i, ii, and iii) in the viral replication origin and appears to be required for viral dna synthesis (dabrowski, c. c., carmillo, p. j., and schaffer, p. a. (1994) mol. cell. biol. 14, 2545-2555). in the present study, we have partially purified and characterized of-1 from human cells. this protein appears to consist of a tetramer compos ...200010878004
transfusion-associated infections with cytomegalovirus and other human herpesviruses.of all human herpesviruses, human cytomegalovirus (hcmv) is the most significant cause of transfusion-associated (ta) morbidity and mortality. the problem of ta hcmv infection differs from that of other transfusion-transmitted infections in that only certain groups of patients require hcmv-free blood or blood components, i.e. seronegative pregnant women, premature infants of low birth weight who are born to seronegative mothers, seronegative recipients of allogeneic bone marrow transplants from ...200010878482
transduction of human pancreatic tumor cells with vesicular stomatitis virus g-pseudotyped retroviral vectors containing a herpes simplex virus thymidine kinase mutant gene enhances bystander effects and sensitivity to ganciclovir.we examined the suitability of moloney murine leukemia virus (mlv) 4070a-, cat endogenous virus (cev) rd114-, or vesicular stomatitis virus g (vsv-g)-pseudotyped retroviruses containing the humanized enhanced green fluorescent protein (hegfp) or one of two herpes simplex virus thymidine kinase (hsv-tk) genes to transduce and provide gene expression in human pancreatic tumor cells. fluorescence-activated cell sorter analysis demonstrated that vsv-g-pseudotyped hegfp vector infected a greater perc ...200010880025
design, synthesis, and biological evaluation of tricyclic nucleosides (dimensional probes) as analogues of certain antiviral polyhalogenated benzimidazole ribonucleosides.the polyhalogenated benzimidazole nucleosides 2,5, 6-trichloro-1-(beta-d-ribofuranosyl)benzimidazole (tcrb) and the 2-bromo analogue (bdcrb) were synthesized in our laboratory and established as potent and selective inhibitors of human cytomegalovirus (hcmv) with a novel mode of action. in an effort to study the behavior of the key substructure in a dimensionally extended manner and probe the spatial limitation of the target enzyme(s), a series of 2-substituted 6, 7-dichloro-1-(beta-d-ribofurano ...200010882370
6-n-acyltriciribine analogues: structure-activity relationship between acyl carbon chain length and activity against hiv-1.triciribine (tcn) and triciribine-5'-monophosphate (tcn-p) are active against hiv-1 at submicromolar concentrations. in an effort to improve and better understand this activity, we have conducted a structure-activity relationship study to explore the tolerance of tcn to structural modifications at the 6-position. a number of 6-n-acyltriciribine analogues were synthesized and evaluated for antiviral activity and cytotoxicity. the cytotoxicity of these compounds was minimal in three human cell lin ...200010882373
mature dendritic cells infected with herpes simplex virus type 1 exhibit inhibited t-cell stimulatory capacity.mature dendritic cells (dc) are the most potent antigen-presenting cells within the entire immune system. interference with the function of these cells therefore constitutes a very powerful mechanism for viruses to escape immune responses. several members of the herpesviridae family have provided examples of such escape strategies, including interference with antigen presentation and production of homologous cytokines. in this study we investigated the infection of mature dc with herpes simplex ...200010888653
a prospective study of cytomegalovirus, herpes simplex virus 1, and coronary heart disease: the atherosclerosis risk in communities (aric) study.conflicting evidence exists implicating infectious disease in the pathological processes leading to coronary heart disease (chd). the objective of this article is to describe the relationship of previous infection with cytomegalovirus (cmv) and herpes simplex virus 1 to incident chd in a population-based cohort study.200010888976
percutaneous gene therapy using recombinant adenoviruses encoding human herpes simplex virus thymidine kinase, human pai-1, and human nos3 in balloon-injured porcine coronary arteries.local intracoronary delivery of recombinant adenoviruses expressing anti-migratory or anti-proliferative proteins including human constitutive endothelial nitric oxide synthase (nos3), plasminogen activator inhibitor 1 (pai-1), or herpesvirus thymidine kinase (tk) (combined with ganciclovir) was used to prevent neointimal formation in porcine coronary arteries. after balloon injury of the left anterior descending (lad) coronary artery, animals received an intramural injection of adenovirus (1.5 ...200010890742
the catalytic subunit of herpes simplex virus type 1 dna polymerase contains a nuclear localization signal in the ul42-binding region.the herpes simplex virus type 1 dna polymerase consists of a catalytic subunit (pol or ul30) and a processivity factor (ul42). the pol/ul42 interaction, which occurs through the extreme c-terminus of pol, is essential for hsv-1 replication and thus represents a valid target for drug inhibition. we recently showed (a. loregian et al. (1999) proc. natl. acad. sci. usa 96, 5221-5226) that an oligopeptide corresponding to the 27 c-terminal amino acids of pol, when delivered into herpes simplex virus ...200010891416
enhanced green fluorescent protein fusion proteins of herpes simplex virus type 1 thymidine kinase and cytochrome p450 4b1: applications for prodrug-activating gene therapy.to monitor therapeutic transgene expression, we developed fusion genes of enhanced green fluorescent protein (egfp) with two different prodrug-activating enzyme genes: herpes simplex virus type 1 thymidine kinase (hsv-tk) and rabbit cytochrome p450 4b1 (cyp4b1). expression of the resulting fusion proteins, tk-egfp and 4b1-egfp, rendered transduced human and rodent glioma cells sensitive to cytotoxic treatment with the corresponding prodrugs ganciclovir and 4-ipomeanol. ganciclovir and 4-ipomeano ...200010830728
plasmid dna encoding ifn-alpha 1 antagonizes herpes simplex virus type 1 ocular infection through cd4+ and cd8+ t lymphocytes.the present study was undertaken to further characterize the anti-viral efficacy of a plasmid dna encoding ifn-alpha1 against ocular herpes simplex virus type 1 (hsv-1) infection. in mice ocularly treated with plasmid dna encoding ifn-alpha 1, the efficacy of the transgene was inversely proportional to the amount of virus used to infect the mice. ocular treatment of mice with the ifn-alpha 1 transgene was the only mucosal route tested that showed efficacy against ocular hsv-1 infection compared ...200010843699
the mal proteolipid is necessary for the overall apical delivery of membrane proteins in the polarized epithelial madin-darby canine kidney and fischer rat thyroid cell lines.the mal proteolipid has been recently demonstrated as being necessary for correct apical sorting of the transmembrane influenza virus hemagglutinin (ha) in madin-darby canine kidney (mdck) cells. the fact that, in contrast to mdck cells, fischer rat thyroid (frt) cells target the majority of glycosylphosphatidylinositol (gpi)-anchored proteins to the basolateral membrane provides us with the opportunity to determine the role of mal in apical transport of membrane proteins under conditions in whi ...200010848627
herpes simplex virus: the importance of asymptomatic shedding.herpes simplex virus (hsv) is frequently shed after infection of the genital or perianal area. hsv shedding, as determined by culture, occurs on about 3% of days for immunocompetent women and men, and more for persons with hiv infection or if measured by polymerase chain reaction (pcr). most horizontal and vertical transmission of hsv occurs during unrecognized or asymptomatic shedding, and the majority of hsv-2-infected persons are unaware of their infection. many persons with 'asymptomatic' hs ...200010855766
testing for type-specific antibody to herpes simplex virus--implications for clinical practice.recently, assays that can distinguish between antibody to herpes simplex virus (hsv) types 1 and 2 have become available. these tests not only make it possible to better define infection in symptomatic patients and their sexual partners but also to identify asymptomatic infected individuals who may, nevertheless, be infectious. type-specific antibody tests for hsv have several potential applications. they have a clear role in helping to define the worldwide distribution and pattern of hsv infect ...200010855767
atp-dependent localization of the herpes simplex virus capsid protein vp26 to sites of procapsid maturation.the herpes simplex virus type 1 (hsv-1) capsid shell is composed of four major polypeptides, vp5, vp19c, vp23, and vp26. vp26, a 12-kda polypeptide, is associated with the tips of the capsid hexons formed by vp5. mature capsids form upon angularization of the shell of short-lived, fragile spherical precursors termed procapsids. the cold sensitivity and short-lived nature of the procapsid have made its isolation and biochemical analysis difficult, and it remains unclear whether procapsids contain ...200010627558
the role of natural killer cells in protection of mice against death and corneal scarring following ocular hsv-1 infection.c57bl/6 mice depleted of nk (natural killer) cells with anti-asialo-gm1 antibody were more susceptible to lethal hsv-1 ocular challenge (12% survival) than control c57bl/6 mice (100% survival), cd4+ depleted mice (100% survival), cd8+ depleted mice (80% survival), or macrophage depleted mice (85% survival). nk depletion also resulted in significantly higher levels of hsv-1 induced corneal scarring than was seen with any of the other groups. c57bl/6 mice depleted of nk cells with pk136 (anti-nk1. ...200010774588
synthesis and antiviral activity of 3-(beta-d-ribofuranosyl)-1,2,4-oxadiazole-5-carboxamide.3-(beta-d-ribofuranosyl)-1,2,4-oxadiazole-5-carboxamide (5) was prepared by condensation reaction of amidoxime 6 with monoethyl oxaloyl chloride followed by reaction with ammonia. the compound 5, however, did not exhibit any significant activity against herpes simplex virus type-i (hsv-i) and semliki forest virus (sfv).200010893705
neutral sphingomyelinase-inhibiting guanidines prevent herpes simplex virus-1 replication.we synthesized a series of new guanidinium derivatives and studied the inhibitory activity on both neutral sphingomyelinase and herpes simplex virus-1 (hsv-1) replication. the lipophilic quality of the molecules was found to be correlated with the inhibitory potential of the compounds. undecylidene-aminoguanidine was superior to derivatives with 10, 8 or 6 carbon atoms whereas propylidene-aminoguanidine was completely inactive. decylidene-aminoguanidine was the most active derivative, with 10 ca ...200010894556
evaluation of tta-mediated gene activation system on human cytomegalovirus and herpes simplex virus type-1 infections.the tetracycline-controlled transactivator (tta)-mediated gene activation system was examined in virus infected cells to determine its role in the control of gene expression. in the presence of tta, the gene expression from the teto-modified minimal promoter was efficiently activated in the uninfected cells, whereas essentially no activation was observed from the only minimal promoter without the seven direct repeats of 42 bp teto sequences. however, essentially no activation was observed when o ...200010896059
treatment with meliacine, a plant derived antiviral, prevents the development of herpetic stromal keratitis in mice.herpetic stromal keratitis is caused by ocular infection with herpes simplex virus type 1 (hsv-1) and constitutes a leading cause of human blindness. the effect of meliacine, an antiviral compound isolated from leaves of melia azedarach l. that inhibits hsv-1 replication in vitro, was examined on experimental corneal hsv-1 inoculation in balb/c mice. mice were inoculated with hsv-1 strain kos at their corneas after abrasion. meliacine was administered topically 3 times a day for 4 days beginning ...200010897066
hsv-1 amplicon vectors--simplicity and versatility. 200010899823
the conserved carboxyl-terminal half of herpes simplex virus type 1 regulatory protein icp27 is dispensable for viral growth in the presence of compensatory mutations.icp27 is an essential herpes simplex virus type 1 (hsv-1) immediate-early protein that regulates viral gene expression by poorly characterized mechanisms. previous data suggest that its carboxyl (c)-terminal portion is absolutely required for productive viral infection. in this study, we isolated m16r, a second-site revertant of a viral icp27 c-terminal mutant. m16r harbors an intragenic reversion, as demonstrated by the fact that its cloned icp27 allele can complement the growth of an hsv-1 icp ...200010906189
molecular localisation of a g-protein mrna using differential display and in situ hybridization.defining molecular repertoires within virally infected tissues of the nervous system may provide insight into the pathogenesis of, and immunity to, neurotropic viruses. here we report the application of such a method, namely mrna differential display (dd), to the identification of mrnas that are expressed at different levels in herpes simplex virus (hsv) infected nervous tissue from immunocompetent and cd8(+) lymphocyte depleted mice. small amounts of input rna can be used by dd, making the meth ...200010906495
association between clinical disease activity and epstein-barr virus reactivation in ms.to assess the potential significance of epstein-barr virus (ebv) reactivation in disease activity in ms patients.200010908887
conformational lability of herpesvirus protein vp22.the herpesvirus protein vp22 traffics between cells, being exported from expressing cells in a non-golgi-dependent manner and localizing in the nuclei of surrounding cells. this transport is retained in certain vp22 fusion proteins, making vp22 a candidate for use in macromolecular drug delivery. in an effort to understand the physical basis for this activity, we have initiated structural studies of vp22.c1, the c-terminal half of vp22, which possesses the full transport activity of the native p ...200010913125
expression of intracellular ifn-gamma in hsv-1-specific cd8+ t cells identifies distinct responding subpopulations during the primary response to infection.cutaneous infection in the footpads of c57bl/6 mice with hsv-1 results in an accumulation of activated (cd44high cd25+) cd8+ t cells within the draining popliteal lymph node (pln). these studies were undertaken to evaluate the frequency and phenotype of the cd8+ t cell population within the pln, recognizing the single immunodominant hsv-1 epitope derived from the viral envelope glycoprotein, glycoprotein b (gb), using an intracellular ifn-gamma-staining assay. it revealed that approximately 6% o ...200010925295
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
intratumoral spread and increased efficacy of a p53-vp22 fusion protein expressed by a recombinant adenovirus.in vitro experiments have demonstrated intercellular trafficking of the vp22 tegument protein of herpes simplex virus type 1 from infected cells to neighboring cells, which internalize vp22 and transport it to the nucleus. vp22 also can mediate intercellular transport of fusion proteins, providing a strategy for increasing the distribution of therapeutic proteins in gene therapy. intercellular trafficking of the p53 tumor suppressor protein was demonstrated in vitro using a plasmid expressing fu ...200111507218
u(l)31 and u(l)34 proteins of herpes simplex virus type 1 form a complex that accumulates at the nuclear rim and is required for envelopment of nucleocapsids.the herpes simplex virus type 1 (hsv-1) u(l)34 protein is likely a type ii membrane protein that localizes within the nuclear membrane and is required for efficient envelopment of progeny virions at the nuclear envelope, whereas the u(l)31 gene product of hsv-1 is a nuclear matrix-associated phosphoprotein previously shown to interact with u(l)34 protein in hsv-1-infected cell lysates. for these studies, polyclonal antisera directed against purified fusion proteins containing u(l)31 protein fuse ...200111507225
cutting edge: myeloid complement c3 enhances the humoral response to peripheral viral infection.hsv-1 is the causative agent of cutaneous lesions, commonly referred to as cold sores. primary exposure to the virus ordinarily occurs through the periphery, in particular through abraded skin or mucosal membranes. under certain circumstances (e.g., in neonatals or aids patients), the infection becomes disseminated, often with severe consequences. spread of hsv-1 is limited by virus-specific ab. the development of an efficient humoral response to the virus is dependent on innate immunity compone ...200111509581
a first step toward understanding membrane fusion induced by herpes simplex virus.in this issue of molecular cell, carfí et al. present the x-ray structure of the n-terminal domains of hvea, a tnf receptor family member, in complex with herpes simplex virus gd, providing a first step to understanding the herpesvirus mode of membrane fusion.200111511354
integrating retroviral cassette extends gene delivery of hsv-1 expression vectors to dividing cells.retroviral vectors have long been used in a wide variety of gene transfer applications but have certain drawbacks, such as small cargo size, limited tropism, and low titers. hsv expression vectors overcome these disadvantages, but, because they persist in target cells as nonreplicative episomes, they are not retained in all the progeny of dividing cells. chimeric hsv/aav products that can mediate transgene integration in human mitotic cells have been constructed, but, to date, genetic modificati ...200111515376
differences in pathogenicity of herpes simplex virus serotypes 1 and 2 may be observed by histopathology and high-resolution magnetic resonance imaging in a murine encephalitis model.the mouse model for herpes simplex-induced encephalitis (hse) is an established preclinical tool for evaluating the efficacy of new therapeutic interventions. we evaluated the utility of high-resolution in vivo mri in observing the progression of experimental hse during the first week postinfection. female balb/c mice were inoculated intracerebrally with hsv-1 or hsv-2 by microinjection. each animal was evaluated daily by high-resolution (4.7 tesla) t(2) weighted mri and clinical disease scoring ...200111517383
infection and establishment of latency in the dog brain after direct inoculation of a nonpathogenic strain of herpes simplex virus-1.a number of diseases affecting the cns occur in the dog and can be used as models for gene therapy in a large brain. hsv-1 has several potential advantages as a vector to transfer genes into the cns. however, the ability of hsv-1 to infect cns cells varies among species and no information was available for the dog. when the nonpathogenic 1716 strain of hsv-1 was injected into the brains of normal dogs it established a latent infection without signs of pathology. thus, it appears to be suitable a ...200111517387
lightcycler multiplex pcr for the laboratory diagnosis of common viral infections of the central nervous system.a conventional multiplex pcr assay that detects herpes simplex virus type 1 (hsv-1), hsv-2, varicella-zoster virus, and enteroviruses for the diagnosis of central nervous system infections was modified to be performed using the lightcycler system. the sensitivity of detection of each of the viruses using the lightcycler assay was compared to that of the conventional assay using external quality assessment material. the assays had equivalent sensitivities, but the lightcycler assay was more rapid ...200111526128
direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors.biodistribution, magnitude and duration of a therapeutic transgene's expression may be assessed by linking it to the expression of a positron emission tomography (pet) reporter gene (prg) and then imaging the prg's expression by a pet reporter probe (prp) in living animals. we validate the simple approach of co-administering two distinct but otherwise identical adenoviruses, one expressing a therapeutic transgene and the other expressing the prg, to track the therapeutic gene's expression. two p ...200111526454
comparison of chemicon simulfluor direct fluorescent antibody staining with cell culture and shell vial direct immunoperoxidase staining for detection of herpes simplex virus and with cytospin direct immunofluorescence staining for detection of varicella-zoster virus.a new rapid direct immunofluorescence assay, the simulfluor direct fluorescent-antibody (dfa) assay, which can simultaneously detect herpes simplex virus types 1 and 2 (hsv-1 and -2) and varicella-zoster virus (vzv), was evaluated in comparison with our current standard procedures of (i) shell vial direct immunoperoxidase (shell vial ip) staining and cell culture for detection of hsv and (ii) cytospin dfa staining for vzv detection. a total of 517 vesicular, oral, genital, and skin lesion specim ...200111527802
acute effects of purified and uv-inactivated herpes simplex virus type 1 on the hypothalamo-pituitary-adrenocortical axis.herpes simplex virus type 1 (hsv-1) is a common cause of viral encephalitis, manifested by neuroendocrine and behavioral changes. we have previously demonstrated that hsv-1 induces marked hypothalamo-pituitary-adrenocortical (hpa) axis activation. in this study we characterized the acute effects of hsv-1 on the hpa axis occurring before viral replication and appearance of clinical signs of encephalitis. since in previous studies we used crude virus preparations which may contain immune factors p ...200111528217
activation of interferon response factor-3 in human cells infected with herpes simplex virus type 1 or human cytomegalovirus.activation of cellular interferon-stimulated genes (isgs) after infection with herpes simplex virus type 1 (hsv-1) or human cytomegalovirus (hcmv) was investigated. the level of isg54-specific rna in human fetal lung (hfl) or human foreskin (bj) fibroblasts increased substantially after infection with either virus in the presence of cycloheximide. hsv-1 particles lacking glycoprotein d or glycoprotein h failed to induce isg54-specific rna synthesis, demonstrating that entry of virus particles ra ...200111533154
direct and sensitive detection of a human virus by rupture event scanning.we have developed a sensitive, economical method that directly detects viruses by making use of the interaction between type 1 herpes simplex virus (hsv1) and specific antibodies covalently attached to the oscillating surface of a quartz crystal microbalance (qcm). the virions were detached from the surface by monotonously increasing the amplitude of oscillation of the qcm, while using the qcm to sensitively detect the acoustic noise produced when the interactions were broken. we term this proce ...200111533641
polymerase chain reaction as a diagnostic adjunct in herpesvirus infections of the nervous system.polymerase chain reaction (pcr) is a powerful technique that allows detection of minute quantities of dna or rna in cerebrospinal fluid (csf), vesicle and endoneurial fluids, blood, fresh-frozen, and even formalin-fixed tissues. various infectious agents can be detected with high specificity and sensitivity, including bacteria, parasites, rickettsia and viruses. pcr analysis of csf has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesvirus ...200111556691
a kinetic analysis of substrate recognition by uracil-dna glycosylase from herpes simplex virus type 1.uracil-dna glycosylase (udg) is responsible for the removal of uracil from dna. it has previously been demonstrated that udg exhibits some sequence dependence in its activity, although this has not been well characterised. this study has investigated the sequence-dependent activity of udg from herpes simplex virus type-1 (hsv-1). a more detailed analysis has been possible by using both kinetic and binding assays with a variety of different oligonucleotide substrates. the target uracil has been p ...200111557818
[aetiopathogenesis of bell's idiopathic peripheral facial palsy].bell's facial palsy is a common condition with an incidence varying between 11.5 and 40.2 cases per 100,000 persons per year. however, some aspects of its aetiopathogenesis are still not clear.200111562829
acyclic/carbocyclic guanosine analogues as anti-herpesvirus agents.several guanosine analogues, i.e. acyclovir (and its oral prodrug valaciclovir), penciclovir (in its oral prodrug form, famciclovir) and ganciclovir, are widely used for the treatment of herpesvirus [i.e. herpes simplex virus type 1 (hsv-1), and type 2 (hsv-2), varicella-zoster virus (vzv) and/or human cytomegalovirus (hcmv)] infections. in recent years, several new guanosine analogues have been developed, including the 3-membered cyclopropylmethyl and -methenyl derivatives (a-5021 and synguanol ...200111563039
seroprevalence of herpes simplex virus types 1 and 2 in hiv-infected and uninfected homosexual men in a primary care setting.genital herpes is usually caused by herpes simplex virus type 2 (hsv-2), with infections often being unrecognised by patients and/or clinicians. hsv-2 infections may be a risk factor for the transmission of human immunodeficiency virus (hiv) infection. reliable tests for type-specific hsv antibodies are now readily available.200111564596
generation of adenoviruses encoding the herpes simplex virus vhs gene: a novel strategy to generate adenoviruses expressing genes toxic to producer cells.adenovirus vectors expressing suicide genes represent a promising approach for cancer gene therapy. we wanted to determine whether the virion host shutoff (vhs) gene of herpes simplex virus could be used as a suicide gene for gene therapy of glioblastomas. the vhs gene was cloned downstream of the glial fibrillary acidic protein promoter to direct tissue-specific expression, and recombinant adenoviruses were generated in 293 cells. viruses, which contained the vhs gene but did not express it, co ...200111571534
adenovirus-mediated expression of hsv1-tk or fas ligand induces cell death in primary human glioma-derived cell cultures that are resistant to the chemotherapeutic agent ccnu.due to minimal treatment success with surgery, radiotherapy, and chemotherapy, the aim of this study was to test the therapeutic potential of gene therapy for the treatment of glioblastoma multiforme (gbm). we have quantitatively analyzed two gene therapy approaches using short-term human glioma cell cultures derived from surgical biopsies (designated in859, in1612, in2045, in1760, and in1265) and compared the results of gene therapy with the chemosensitivity of the same cells. all of the glioma ...200111571537
complement c4 deficiency and hla homozygosity in patients with frequent intraoral herpes simplex virus type 1 infections.three consecutive patients with no apparent immunodeficiency who had frequent intraoral herpes simplex type 1 recurrences, a rare complication of herpes simplex virus infection, were found to have a total deficiency of either the a or b isotype of the complement component c4 and to be homozygous for the studied hla antigens. a combination of hla homozygosity, which may lead to impaired t cell recognition of viral peptides, and deficiency in the classical complement pathway, which can compromise ...200111577377
a null mutation in the gene encoding the herpes simplex virus type 1 ul37 polypeptide abrogates virus maturation.the tegument is an integral and essential structural component of the herpes simplex virus type 1 (hsv-1) virion. the ul37 open reading frame of hsv-1 encodes a 120-kda virion polypeptide which is a resident of the tegument. to analyze the function of the ul37-encoded polypeptide a null mutation was generated in the gene encoding this protein. in order to propagate this mutant virus, transformed cell lines that express the ul37 gene product in trans were produced. the null mutation was transferr ...200111581394
multiple herpetic whitlow lesions in a 4-year-old girl: case report and review of the literature.herpetic whitlow is a herpes simplex virus type 1 or 2 infection of the fingers characterised by erythema and painful, non-purulent vesicles. in children it typically occurs after auto-inoculation from herpes stomatitis, herpes labialis or genitalis. occasionally, person-to-person transmission occurs from family members with herpes labialis. we report a 4-year-old girl with multiple herpetic whitlows secondary to herpetic stomatitis and present a review of the medical literature based on a syste ...200111585074
primary graft failure caused by herpes simplex virus type 1. 200111588438
combination vascular delivery of herpes simplex oncolytic viruses and amplicon mediated cytokine gene transfer is effective therapy for experimental liver cancer.herpes simplex type i (hsv)-based vectors have been used experimentally for suicide gene therapy, immunomodulatory gene delivery, and direct oncolytic therapy. the current study utilizes the novel concept of regional delivery of an oncolytic virus in combination with or serving as the helper virus for packaging herpes-based amplicon vectors carrying a cytokine transgene, with the goal of identifying if this combination is more efficacious than either modality alone.200111591892
immunohistological study of infiltrated cells and cytokines in murine herpetic keratitis.to identify localization and kinetics of infiltrated cells and cytokines in murine herpetic keratitis.200111594984
comparison of different forms of herpes simplex replication-defective mutant viruses as vaccines in a mouse model of hsv-2 genital infection.some subunit vaccines composed of herpes simplex virus (hsv) glycoproteins have been shown to protect guinea pigs against primary and recurrent genital infection by hsv-2. however, these vaccines were ineffective or only marginally effective in clinical trials. to attempt to define an animal model that would better discriminate the protective capacity of different vaccine formulations, we have examined the requirements for vaccine-induced protection against hsv-2 infection and disease in a mouse ...200111601897
mycobacterial and nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus infection: a prospective, cohort study.a prospective observational study was done to describe nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus (hiv) infection.200111602023
temporal regulation of herpes simplex virus type 2 vp22 expression and phosphorylation.the vp22 protein of herpes simplex virus type 2 (hsv-2) is a major component of the virion tegument. previous work with hsv-1 indicated that vp22 is phosphorylated during infection, and phosphorylation may play a role in modulating vp22 localization in infected cells. it is not clear, however, when phosphorylation occurs in infected cells or how it is regulated. less is known about the synthesis and phosphorylation of hsv-2 vp22. to study the complete biosynthetic history of hsv-2 vp22, we gener ...200111602713
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