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ocular reactivation phenotype of hsv-1 strain f(mp)e, a corticosteroid-sensitive strain.elucidate the ocular reactivation of hsv-1 strain f(mp)e.200312815548
an hsv-1 chimeric containing hsv-2 latency associated transcript (lat) sequences has significantly reduced adrenergic reactivation in the rabbit eye model.both hsv-1 and hsv-2 express lat during viral latency. previous studies indicated that deletion of either lat impairs viral reactivation from latency, but that the hsv-1 lat confers the ability to reactivate efficiently from trigeminal ganglia onto hsv-2. we sought to determine whether the hsv-2 lat could function in the context of hsv-1.200312815550
establishment and maintenance of hsv latent infection is mediated through correct splicing of the lat primary transcript.to study the effect of the splicing of hsv-1 latency-associated transcript (lat) on viral latency, we constructed two mutant viruses (fhlambda+ and fhlambda-) in which the 168-bp hpai-hpai fragment within the 2-kb lat intron was replaced by a 447-bp bacteriophage lambda sequence. the lambda dna was inserted in opposite orientations in fhlambda+ and fhlambda-. the mutation in fhlambda+ disrupted the splicing of lat primary transcript and altered both lat exon and intron, whereas the mutation in f ...200312890636
active site mutants of drosophila melanogaster multisubstrate deoxyribonucleoside kinase.the multisubstrate deoxyribonucleoside kinase of drosophila melanogaster (dm-dnk) is sequence-related to three human deoxyribonucleoside kinases and to herpes simplex virus type-1 thymidine kinase. dm-dnk phosphorylates both purine and pyrimidine deoxyribonucleosides and nucleoside analogues although it has a preference for pyrimidine nucleosides. we performed site-directed mutagenesis on residues that, based on structural data, are involved in substrate recognition. the aim was to increase the ...200312823558
pml residue lysine 160 is required for the degradation of pml induced by herpes simplex virus type 1 regulatory protein icp0.during the early stages of herpes simplex virus type 1 (hsv-1) infection, viral immediate-early regulatory protein icp0 localizes to and disrupts cellular nuclear structures known as pml nuclear bodies or nd10. these activities correlate with the functions of icp0 in stimulating lytic infection and reactivating quiescent hsv-1. the disruption of nd10 occurs because icp0 induces the loss of the sumo-1-modified forms of pml and the subsequent proteasome-mediated degradation of the pml protein. the ...200312885887
the effects of xalatan on the recovery of ocular herpes simplex virus type 1 (hsv-1) in the induced reactivation and spontaneous shedding rabbit models.xalatan treatment has been reported both clinically and experimentally to promote recurrences of herpetic keratitis. our goal was to determine the effects of topical xalatan and its components on the recovery of ocular herpes simplex virus type 1 (hsv-1) in the induced reactivation (ir) and spontaneous shedding (ss) hsv-1/nzw rabbit latency models using virological outcome measures.200312828841
transactivation of a viral target gene by herpes simplex virus icp27 is posttranscriptional and does not require the endogenous promoter or polyadenylation site.icp27 is an essential herpes simplex virus type 1 (hsv-1) immediate-early protein that stimulates viral mrna expression from many viral delayed-early and late genes during infection. one hsv-1 late gene which is highly dependent on icp27 during infection is that encoding the glycoprotein c (gc). here we report that the gc gene is specifically transactivated by icp27 in transfected vero cells. using various gc plasmid constructs, we show that icp27's stimulatory effects are independent of the gc ...200312941897
structure-based mutagenesis of herpes simplex virus glycoprotein d defines three critical regions at the gd-hvea/hvem binding interface.herpes simplex virus (hsv) entry into cells requires the binding of glycoprotein d (gd) to one of several cell surface receptors. the crystal structure of gd bound to one of these receptors, hvea/hvem, reveals that the core of gd comprises an immunoglobulin fold flanked by a long c-terminal extension and an n-terminal hairpin loop. hvea is a member of the tumor necrosis factor receptor family and contains four cysteine-rich domains (crds) characteristic of this family. fourteen amino acids withi ...200312829851
in vitro antiviral activities of caesalpinia pulcherrima and its related flavonoids.the aim of this study was to search for new antiviral agents from chinese herbal medicine. pure flavonoids and aqueous extracts of caesalpinia pulcherrima swartz were used in experiments to test their influence on a series of viruses, namely herpesviruses (hsv-1, hsv-2) and adenoviruses (adv-3, adv-8, adv-11). the ec50 was defined as the concentration required to achieve 50% protection against virus-induced cytopathic effects, and the selectivity index (si) was determined as the ratio of cc50 (c ...200312837746
"translocatory proteins" and "protein transduction domains": a critical analysis of their biological effects and the underlying mechanisms.it has been suggested that several proteins, termed "translocatory" or "messenger" proteins, can move between living cells-exiting the cell of synthesis via an uncharacterized secretory pathway and entering adjacent cells by a nonendocytic mechanism that is active even at 4 degrees c. these activities, which have been mapped to short, highly basic regions termed "protein transduction domains" (ptds), have engendered considerable interest in the gene therapy and vaccine research communities. if t ...200312842424
engineering of rnase p ribozyme for gene-targeting applications.ribonuclease p (rnase p) is a ubiquitous ribonucleoprotein complex responsible for the biosynthesis of trna. this enzyme from escherichia coli contains a catalytic rna subunit (m1 ribozyme) and a protein subunit (c5 cofactor). m1 ribozyme cleaves an rna helix that resembles the acceptor stem and t-stem structure of its natural trna substrate. when covalently linked with a guide sequence, m1 rna can be engineered into a sequence-specific endonuclease, m1gs ribozyme, which can cleave any target rn ...200312957377
[antiviral activity of some 5-arylethynyl 2'-deoxyuridine derivatives].5-(3-perylenylethynyl)-2'-deoxyuridine was prepared by cross-linking 5-iodo-2'-deoxyuridine derivatives with 3-ethynylperylene followed by deprotection. 5-(1-perylenylethynyl)-, 5-(3-perylenylethynyl)-, and 5-[4-(2-benzoxazolyl)phenylethynyl]-2'-deoxyuridine were found to inhibit in vero cells the replication of type 1 herpes simplex virus and its drug-resistant strains.200312845804
blocking 4-1bb/4-1bb ligand interactions prevents herpetic stromal keratitis.herpetic stromal keratitis (hsk) is a chronic inflammatory process in corneal stroma that results from recurrent hsv type 1 infection. we used the murine model of hsk to demonstrate the importance of the interaction between an inducible t cell costimulatory receptor, 4-1bb, and its ligand, 4-1bb ligand (4-1bbl), in the development of this disease. in balb/c mice, hsk ordinarily induced by infection with the re strain of herpes was prevented by blocking 4-1bb/4-1bbl interaction, either by deletin ...200312847221
ras signalling pathway: a gateway for hsv-1 infection. 200312847302
the degradation of promyelocytic leukemia and sp100 proteins by herpes simplex virus 1 is mediated by the ubiquitin-conjugating enzyme ubch5a.infected cell protein 0 (icp0) of herpes simplex virus 1 expresses two e3 ubiquitin (ub) ligase activities mapping in the domains encoded by exons 2 and 3, respectively. site 1 (exon 3) is responsible for the degradation of the e2 ub-conjugating enzyme cdc34 whereas site 2 (exon 2) is associated with a ring finger and has been shown to mediate the degradation of promyelocytic leukemia (pml) and sp100 proteins and the dispersal of nuclear domain 10 (nd10). in in vitro assays site 2 polyubiquityla ...200312855769
development of a novel non-human primate model for preclinical gene vector safety studies. determining the effects of intracerebral hsv-1 inoculation in the common marmoset: a comparative study.the owl monkey (aotus trivirgatus) has served as the standard non-human primate model of herpes simplex virus-1 (hsv-1) infection because it is highly susceptible to hsv-1 encephalitis. owl monkeys, however, are expensive, difficult to obtain, and difficult to maintain in captivity, thus greatly hampering the efficiency of preclinical gene therapy trials for brain tumors using hsv-1-based vectors. we have therefore compared the susceptibility of the common marmoset (callithrix jacchus) with the ...200312858187
the dual role of cd8+ t lymphocytes in the development of stress-induced herpes simplex encephalitis.despite the generally restrictive nature of the blood-brain barrier (bbb), circulating lymphocytes can infiltrate into the central nervous system (cns) during a variety of disease states. although the contributions of these lymphocytes to cns-associated disease have been identified in some viral models, the factors which govern this infiltration following herpes simplex virus (hsv) infection remain to be elucidated. we have developed a murine model of hsv encephalitis (hse) to define the relatio ...200312864968
do infectious agents play a role in dementia? 200312875814
role of acyclovir gel in herpes simplex: clinical implications.acyclovir (acy) is effective in the treatment of herpes simplex (hsv-1) & (hsv-2) but has systemic toxic effects if given orally or intravenously. acy has not been used to treat the disease topically due to poor drug penetration into skin. a novel 1% liposomal acy topical gel in a 5% hydroxypropylmethyl cellulose (hpmc) k4m gel base has been developed and clinically evaluated in hsv-1 and hsv-2 patients.200312883465
herpes simplex encephalitis. 200312892957
the herpes simplex virus (hsv) protein icp34.5 is a virion component that forms a dna-binding complex with proliferating cell nuclear antigen and hsv replication proteins.the replicative ability of icp34.5-null herpes simplex virus (hsv) is cell type and state dependent. in certain cells, icp34.5 interacts with protein phosphatase 1 to preclude host cell protein synthesis shutoff by dephosphorylation of the eukaryotic initiation factor eif-2alpha. however, host cell shutoff is not induced by icp34.5-null hsv in most cells, irrespective of type and state. in general, dividing cells support replication of icp34.5-null hsv; nondividing cells cannot. previously the a ...200312907392
photodynamic inhibition of infection caused by drug-resistant variants of herpes simplex virus type i.membranotropic amphiphilic chromophore merocyanine 540 sensitized photodynamic inhibition of drug-resistant and sensitive variants of type i herpes simplex virus in cultured vero cell. optimal conditions of photodamage to virus particles and infected cells were determined (merocyanine 540 concentration 1 microm, illumination dose 32.5-65.0 kj/m(2), exposure at early stages of infection). infected cells actively bind the photosensitizer, which explains their selective photodamage.200312910315
increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students.a retrospective review of genital herpes simplex virus (hsv) isolates collected in a university student health service over a 9-year period showed that an increasing proportion of isolates were hsv-1 rather than hsv-2. hsv-1 accounted for 78% of all genital isolates in this population by 2001, compared with 31% of isolates in 1993.200314520181
co-detection and discrimination of six human herpesviruses by multiplex pcr-elaha.herpesviruses are a significant cause of human morbidity. traditional approaches to the identification of these viruses require infectious or at least antigenic virus. multiplex pcr (mpcr) is capable of simultaneously amplifying a range of targets from a single preparation of nucleic acids and when combined with a suitable detection assay, it is capable of discriminating each of the amplicons.200314522068
mutations in the n termini of herpes simplex virus type 1 and 2 gds alter functional interactions with the entry/fusion receptors hvem, nectin-2, and 3-o-sulfated heparan sulfate but not with nectin-1.multiple cell surface molecules (herpesvirus entry mediator [hvem], nectin-1, nectin-2, and 3-o-sulfated heparan sulfate) can serve as entry receptors for herpes simplex virus type 1 (hsv-1) or hsv-2 and also as receptors for virus-induced cell fusion. viral glycoprotein d (gd) is the ligand for these receptors. a previous study showed that hvem makes contact with hsv-1 gd at regions within amino acids 7 to 15 and 24 to 32 at the n terminus of gd. in the present study, amino acid substitutions a ...200312915538
synthesis, solution structure analysis and antibody binding of cyclic epitope peptides from glycoprotein d of herpes simplex virus type i.two cyclic peptides with a thioether bond have been synthesised corresponding to the 9-22 (9lkmadpnrfrgkdl(22)) sequence of glycoprotein d (gd-1) of herpes simplex virus. the role of the secondary structure in protein-specific monoclonal antibody recognition was investigated. the sequence selected for this study comprises a strongly antigenic site adopting a beta-turn at residues 14pro-(15)asn. thioether bond was formed between the free thiol group of cysteine or homocysteine inserted in positio ...200314556904
epidemiology of genital herpes (hsv-2) among brothel based female sex workers in bangladesh.a prospective study was carried out to determine the prevalence of herpes simplex type 2 (hsv-2) in bangladeshi female sex workers. serum samples were collected from 463 female prostitutes and tested by elisa using type specific antigens (gg1 and gg2). there were 405 (87.5%) samples seropositive for both hsv-1 and hsv-2, 24 (5.2%) samples were seropositive for only hsv-1, a further 33 (7.1%) samples were seropositive for hsv-2 only and one sample was found to be negative. human immunodeficiency ...200314561051
existence of transdominant and potentiating mutants of ul9, the herpes simplex virus type 1 origin-binding protein, suggests that levels of ul9 protein may be regulated during infection.ul9 is a multifunctional protein required for herpes simplex virus type 1 (hsv-1) replication in vivo. ul9 is a member of the superfamily ii helicases and exhibits helicase and origin-binding activities. we have previously shown that mutations in the conserved helicase motifs of ul9 can have either a transdominant or potentiating effect on the plaque-forming ability of infectious dna from wild-type virus (a. j. malik and s. k. weller, j. virol. 70:7859-7866, 1996). in this paper, the mechanisms ...200312915576
differences in the n termini of herpes simplex virus type 1 and 2 gds that influence functional interactions with the human entry receptor nectin-2 and an entry receptor expressed in chinese hamster ovary cells.amino acid differences at seven positions in the n termini of the glycoproteins d (gds) specified by herpes simplex virus type 1 (hsv-1) and hsv-2 are largely responsible for the significantly higher cell fusion activity of hsv-2 gd with chinese hamster ovary cells expressing human nectin-2 or only an endogenous hamster receptor.200312915581
herpes simplex virus type 1 tegument protein vp22 interacts with taf-i proteins and inhibits nucleosome assembly but not regulation of histone acetylation by inhat.affinity chromatography was used to identify cellular proteins that interact with the herpes simplex virus (hsv) tegument protein vp22. among a small set of proteins that bind specifically to vp22, we identified taf-i (template-activating factor i), a chromatin remodelling protein and close homologue of the histone chaperone protein nap-1. taf-i has been shown previously to promote more ordered transfer of histones to naked dna through a direct interaction with histones. taf-i, as a subunit of t ...200312917472
the bovine herpesvirus-1 lr orf2 is critical for this gene's ability to restore the high wild-type reactivation phenotype to a herpes simplex virus-1 lat null mutant.during neuronal latency of herpes simplex virus (hsv)-1, the latency-associated transcript (lat) is the only viral gene readily detectable. lat is required for the high-level reactivation phenotype in animal models. lat's anti-apoptotic activity was recently demonstrated by our group and it was proposed that lat's anti-apoptotic function is involved in enhancing the reactivation phenotype. recently, using chimeric virus cjlat, it was shown that the reactivation phenotype of lat(-) mutant dlat290 ...200314573802
immunopathogenesis and prevention of uveitis with the behçet's disease-specific peptide linked to cholera toxin b. 200312918685
acute cerebellitis caused by herpes simplex virus type 1.cerebellar disorders due to herpes simplex virus (hsv) infection are rare and always associated with herpes simplex encephalitis. we report 2 cases of severe primary acute cerebellitis caused by hsv type 1 that were identified by nested polymerase chain reaction performed on cerebrospinal fluid samples.200312539091
phenotypic and genotypic methods for the detection of herpes simplex virus serotypes.typing of herpes simplex virus (hsv) into its serotypes plays a major role in epidemiology and management of reactivation. to develop and evaluate a polymerase chain reaction (pcr)-based restriction fragment length polymorphism (rflp) was employed using hae iii and taq i against neutralization test, allele-specific pcr and dna sequencing for the detection of hsv serotypes. neutralization test, allele-specific pcr, dna sequencing and pcr-based rflp were applied simultaneously to 2 standard strain ...200312565159
treatment of human papillomavirus (hpv) type 16-infected cells using herpes simplex virus type 1 thymidine kinase-mediated gene therapy transcriptionally regulated by the hpv e2 protein.human papillomavirus type 16 (hpv-16) is associated with development of anogenital squamous cell cancers (sccs) and their precursor, intraepithelial neoplasia (in). few approaches to the treatment of in to prevent scc are targeted specifically to hpv. we have designed an hpv-specific therapy using the herpes simplex virus type 1 thymidine kinase (hsv-1 tk) gene driven by an hpv-specific promoter in the hpv-16 long control region (lcr) (nucleotide 7450-nucleotide 104), which is regulated by the h ...200312573058
transfer of fgf-2 via hsv-1-based amplicon vectors promotes efficient formation of neurons from embryonic stem cells.the manipulation of embryonic stem (es) cells has a great potential to create cell populations useful for tissue replacement and regeneration of organs. the acquirement of specific cell fates and differentiation into specialized cell types may be obtained by the application of specific growth factors. fibroblast growth factor 2 (fgf-2) has been used for the formation of es cell-derived cns stem cells. in order to achieve high efficiency of gene delivery into stem cells, the use of viral vectors ...200312581849
massive apoptotic cell death in chemically induced rat urinary bladder carcinomas following in situ hsvtk electrogene transfer.gene delivery in current gene therapy studies relies largely on recombinant viral vectors. however, the safety of this method is still under investigation. the effectiveness of in vivo electrogene transfer as a means of gene therapy for rat bladder cancers using the herpes simplex virus 1 thymidine kinase (hsvtk) gene in combination with ganciclovir (gcv) was therefore investigated.200312666188
cytologic detection of cryptococcosis coexisting with herpes simplex virus infection in sputum: use of liquid-based, thin-layer preparations. 200312585041
in vivo replication of an icp34.5 second-site suppressor mutant following corneal infection correlates with in vitro regulation of eif2 alpha phosphorylation.in animal models of herpes simplex virus type 1 (hsv-1) infection, icp34.5-null viruses are avirulent and also fail to grow in a variety of cultured cells due to their inability to prevent rna-dependent protein kinase (pkr)-mediated inhibition of protein synthesis. we show here that the inability of icp34.5 mutants to grow in vitro is due specifically to the accumulation of phosphorylated eif2 alpha. mutations suppressing the in vitro phenotype of icp34.5-null mutants have been described which m ...200312663769
synthesis and antiviral activity of novel erythrofuranosyl imidazo[1,2-a]pyridine c-nucleosides constructed via palladium coupling of iodoimidazo[1,2-a]pyridines and dihydrofuran.2,5,6-trichloro-1-(beta-d-ribofuranosyl)benzimidazole (tcrb) and certain analogues have shown significant activity against human cytomegalovirus. the metabolic instability of the glycosidic linkage in tcrb prompted us to synthesize the structurally similar imidazo[1,2-a]pyridine erythrofuranosyl c-nucleosides. as an approach to the synthesis of polychlorinated imidazo[1,2-a]pyridine c-3-erythrofuranosides, a palladium-based methodology for coupling 2,3-dihydrofuran with chlorinated 3-iodoimidazo ...200312672244
membrane association of vp22, a herpes simplex virus type 1 tegument protein.tegument proteins of herpes simplex virus type 1 (hsv-1) are hypothesized to contain the functional information required for the budding or envelopment process proposed to occur at cytoplasmic compartments of the host cell. one of the most abundant tegument proteins of hsv-1 is the u(l)49 gene product, vp22, a 38-kda protein of unknown function. to study its subcellular localization, a vp22-green fluorescent protein chimera was expressed in transfected human melanoma (a7) cells. in the absence o ...200312663795
regional distribution of antibodies to herpes simplex virus type 1 (hsv-1) and hsv-2 in men and women in ontario, canada.this study estimated the regional and age- and gender-specific seroprevalences of herpes simplex virus type 1 (hsv-1) and hsv-2 in ontario, canada. stored serum specimens from subjects aged 15 to 44 years, including men (n = 979), women not under prenatal care (n = 638), and women under prenatal care (n = 701) submitted for routine viral serology were randomly selected according to regional population size from public health laboratories. hsv-1 and hsv-2 testing was done with the mrl enzyme immu ...200312517830
recent progress in herpes simplex virus immunobiology and vaccine research.herpes simplex virus types 1 and 2 (hsv-1 and hsv-2) cause prevalent, chronic infections that have serious outcomes in some individuals. neonatal herpes may occur when the infant traverses the cervix during maternal genital herpes. genital herpes is a major risk factor for human immunodeficiency virus type 1 transmission. considerable efforts have been made to design and test vaccines for hsv, focusing on genital infection with hsv-2. several protein subunit vaccines based on hsv-2 envelope glyc ...200312525427
polymerase chain reaction as a rapid diagnostic tool for therapy of acute retinal necrosis syndrome.herpesviruses are involved in the pathogenesis of acute retinal necrosis syndrome (arn). a rapid and accurate diagnosis of herpetic infections is crucial for prompt administration of a specific antiviral therapy. the purpose of this study was to evaluate a polymerase chain reaction (pcr)-based assay to detect herpesvirus dna in the aqueous humor of clinical samples from ten patients with uveitis and clinical suspicion of arn. samples were assayed for herpes simplex virus type 1-2 (hsv 1-2), vari ...200312526051
construction of multiply disabled herpes simplex viral vectors for gene delivery to the nervous system. 200312526157
origin-specific unwinding of herpes simplex virus 1 dna by the viral ul9 and icp8 proteins: visualization of a specific preunwinding complex.herpes simplex virus 1 contains three origins of replication; two copies of oris and one of a similar sequence, oril. here, the combined action of multiple factors known or thought to influence the opening of oris are examined. these include the viral origin-binding protein, ul9, and single-strand binding protein icp8, host cell topoisomerase i, and superhelicity of the dna template. by using electron microscopy, it was observed that when icp8 and ul9 proteins were added together to oris-contain ...200312552114
development of a prostate-specific promoter for gene therapy against androgen-independent prostate cancer.androgen ablation has been the standard treatment for metastasized prostate cancer. in most cases, however, prostate cancer cells eventually lose androgen dependency and become refractory to the conventional endocrine therapy. androgen-independent prostate cancer is characterized by a heterogeneous loss of androgen receptor (ar) expression among tumor cells. prostate-specific promoters such as prostate-specific antigen and rat probasin (rpb) promoters have been examined in the development of gen ...200312668132
on call. i'm bothered by cold sores two or three times a year. what are they, and what can i do about them? 200312604445
a single amino acid substitution in herpes simplex virus type 1 vp16 inhibits binding to the virion host shutoff protein and is incompatible with virus growth.in addition to its well-established role in the activation of herpes simplex virus immediate-early gene transcription, vp16 interacts with and downregulates the function of the virion host shutoff protein (vhs), thereby attenuating vhs-mediated destruction of viral mrnas and translational arrest at late times of infection. we have carried out two-hybrid analysis in vivo and protein-protein interaction assays in vitro to identify determinants in vp16 necessary for interaction with vhs. the minima ...200312584313
conformational study of linear and cyclic peptides corresponding to the 276-284 epitope region of hsv gd-1.the results of conformational analysis of linear and cyclic peptides from the 276salledpvg(284) sequence of glycoprotein d of herpes simplex virus are presented. the epitope peptides were synthesized by spps and on resin cyclization was applied for preparation of cyclic compounds. circular dichroism spectroscopy, fourier-transform infrared spectroscopy and nuclear magnetic resonance (nmr) were used to determine of the solution structure of both linear and cyclic peptides. the results indicated t ...200312504254
[herpes simplex virus type 1 and type 2]. 200312718030
noninvasive imaging of lentiviral-mediated reporter gene expression in living mice.lentiviral-mediated gene delivery holds significant promise for sustained gene expression within living systems. vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 1-based lentiviral vectors can be used to introduce transgenes in a broad spectrum of dividing as well as nondividing cells. in the current study, we construct a lentiviral vector carrying two reporter genes separated by an internal ribosomal entry site and utilize that virus in delivering both genes ...200312718911
exonuclease-deficient polymerase mutant of herpes simplex virus type 1 induces altered spectra of mutations.the effect of exonuclease activity of the herpes simplex virus dna polymerase (pol) on dna replication fidelity was examined by using the supf mutagenesis assay. the recombinants with exonuclease-deficient pol, containing an integrated supf gene in the thymidine kinase locus (tk), exhibited supf mutation frequencies ranging from 0.14 to 5.6%, consistent with the tk mutation frequencies reported previously (y. t. hwang, b.-y. liu, d. m. coen, and c. b. c. hwang, j. virol. 71:7791-7798, 1997). the ...200312584319
[herpes simplex virus infection]. 200312722213
serial in vivo imaging of the targeted migration of human hsv-tk-transduced antigen-specific lymphocytes.new technologies are needed to characterize the migration, survival, and function of antigen-specific t cells in vivo. here, we demonstrate that epstein-barr virus (ebv)--specific t cells transduced with vectors encoding herpes simplex virus-1 thymidine kinase (hsv-tk) selectively accumulate radiolabeled 2'-fluoro-2'-deoxy-1-beta-d-arabinofuranosyl-5-iodouracil (fiau). after adoptive transfer, hsv-tk+ t cells labeled in vitro or in vivo with [131i]fiau or [124i]fiau can be noninvasively tracked ...200312652311
the stable 2.0-kilobase intron of the herpes simplex virus type 1 latency-associated transcript does not function as an antisense repressor of icp0 in nonneuronal cells.during latency, herpes simplex virus expresses a unique set of latency-associated transcripts (lats). as the 2.0-kb lat intron is complementary to, and overlaps, the 3' end of the icp0 transcript, it has been suggested that the stable lat intron might function as an antisense repressor of icp0 expression. we tested this hypothesis in cell culture by dissociating cis- and trans-acting effects of the 2.0-kb lat, using a series of complementary strategies. initially, we constructed 293t cell lines ...200312610127
icp27 interacts with srpk1 to mediate hsv splicing inhibition by altering sr protein phosphorylation.infection with some viruses can alter cellular mrna processing to favor viral gene expression. we present evidence that herpes simplex virus 1 (hsv-1) protein icp27, which contributes to host shut-off by inhibiting pre-mrna splicing, interacts with essential splicing factors termed sr proteins and affects their phosphorylation. during hsv-1 infection, phosphorylation of several sr proteins was reduced and this correlated with a subnuclear redistribution. exogenous sr proteins restored splicing i ...200312660167
time course of seroconversion by herpeselect elisa after acquisition of genital herpes simplex virus type 1 (hsv-1) or hsv-2.herpeselect hsv-1 and hsv-2 elisas are glycoprotein g-based, type-specific antibody detection tests that are approved by the us food and drug administration for diagnosis of genital herpes.200312671550
enhancement of dna vaccine potency against herpes simplex virus 1 by co-administration of an interleukin-18 expression plasmid as a genetic adjuvant.in this study, the immune-modulatory and vaccine effects of using an interleukin (il)-18 expression plasmid as a genetic adjuvant to enhance dna vaccine-induced immune responses were investigated in a mouse herpes simplex virus 1 (hsv-1) challenge model. balb/c mice were immunized by three intramuscular inoculations of hsv-1 glycoprotein d (gd) dna vaccine alone or in combination with a plasmid expressing mature il-18 peptide. both the serum igg2a/igg1 ratio and t helper 1-type (th1) cytokines [ ...200312621087
mutation of single hydrophobic residue i27, l35, f39, l58, l65, l67, or l71 in the n terminus of vp5 abolishes interaction with the scaffold protein and prevents closure of herpes simplex virus type 1 capsid shells.protein-protein interactions drive the assembly of the herpes simplex virus type 1 (hsv-1) capsid. a key interaction occurs between the c-terminal tail of the scaffold protein (pre-22a) and the major capsid protein (vp5). previously (z. hong, m. beaudet-miller, j. durkin, r. zhang, and a. d. kwong, j. virol. 70:533-540, 1996) it was shown that the minimal domain in the scaffold protein necessary for this interaction was composed of a hydrophobic amphipathic helix. the goal of this study was to i ...200312634364
three-dimensional localization of porf65 in kaposi's sarcoma-associated herpesvirus capsid.of the six herpesvirus capsid proteins, the smallest capsid proteins (scps) share the least sequence homology among herpesvirus family members and have been implicated in virus specificity during infection. the herpes simplex virus-1 (hsv-1) scp was shown to be horn shaped and to specifically bind the upper domain of each major capsid protein in hexons but not in pentons. in kaposi's sarcoma-associated herpesvirus (kshv), the protein encoded by the orf65 gene (porf65) is the putative scp but its ...200312634386
c-terminal region of herpes simplex virus icp8 protein needed for intranuclear localization.the herpes simplex virus single-stranded dna-binding protein, icp8, localizes initially to structures in the nucleus called prereplicative sites. as replication proceeds, these sites mature into large globular structures called replication compartments. the details of what signals or proteins are involved in the redistribution of viral and cellular proteins within the nucleus between prereplicative sites and replication compartments are poorly understood; however, we showed previously that the d ...200312758170
epidemiology of herpes simplex virus types 1 and 2 in germany: what has changed?infections with herpes simplex virus (hsv) types 1 and 2 are widespread in all human populations and result in persistent and latent infections. hsv-1 is commonly responsible for orofacial, hsv-2 more likely causes genital lesions. herpes genitalis is one of the most important sexually transmitted diseases; furthermore, there are severe diseases associated with hsv (e.g., encephalitis). over the last years an increase in clinical manifestations of hsv has been reported, and hsv-1 has been increa ...200312761673
ck2 protein kinase is stimulated and redistributed by functional herpes simplex virus icp27 protein.it has been shown previously (s. wadd, h. bryant, o. filhol, j. e. scott, t.-t. hsieh, r. d. everett, and j. b. clements, j. biol. chem. 274:28991-28998, 2000) that icp27, an essential and multifunctional herpes simplex virus type 1 (hsv-1) protein, interacts with ck2 and with heterogeneous ribonucleoprotein k (hnrnp k). ck2 is a pleiotropic and ubiquitous protein kinase, and the tetrameric holoenzyme consists of two catalytic alpha or alpha' subunits and two regulatory beta subunits. we show he ...200312634389
vp22 flips the switch on cell death. 200312638542
improved herpes simplex virus type 1 amplicon vectors for proportional coexpression of positron emission tomography marker and therapeutic genes.for the development of efficient and safe gene therapy protocols for clinical application it is desirable to determine the tissue dose of vector-mediated therapeutic gene expression noninvasively in vivo. the herpes simplex virus type 1 thymidine kinase gene (hsv-1-tk) has been shown to function as a marker gene for the direct noninvasive in vivo localization of thymidine kinase (tk) expression by positron emission tomography (pet). using bicistronic or multicistronic gene-expressing cassettes w ...200312639307
activation of the human endogenous retrovirus w long terminal repeat by herpes simplex virus type 1 immediate early protein 1.the u3 region of the human endogenous retrovirus w long terminal repeat (herv-w ltr) contains several putative regulatory sequences that regulate the transcription of neighboring cellular genes, as well as viral genes. we found that the ltr-directed transcription of the herv-w can be induced by the herpes simplex virus type 1 (hsv-1) infection. the effect was partly mediated by the action of the hsv-1 immediate early protein 1 (ie1), and required an oct-1 binding site that is located in the ltr. ...200312661764
[amniotic membrane transplantation improves herpetic keratitis by local and not by systemic effects].the immune mediated hsv-1 stromal keratitis (hsk) rapidly improves after amniotic membrane transplantation (amt). this study investigated whether amt modulates the t cell response and whether the anti-inflammatory action of amt is due to local or systemic effects.200312640550
antiviral flavonoids from the root bark of morus alba l.a prenylated flavonoid, moralbanone, along with seven known compounds kuwanon s, mulberroside c, cyclomorusin, eudraflavone b hydroperoxide, oxydihydromorusin, leachianone g and alpha-acetyl-amyrin were isolated from the root bark of morus alba l. leachianone g showed potent antiviral activity (ic(50) = 1.6 microg/ml), whereas mulberroside c showed weak activity (ic(50) = 75.4 microg/ml) against herpes simplex type 1 virus (hsv-1). their structures were elucidated by spectroscopic methods.200312648543
t cell immunity to herpes simplex viruses in seronegative subjects: silent infection or acquired immunity?during the course of investigating t cell responses to hsv among volunteers entering trials of investigational genital herpes vaccines, 6 of the 24 immunocompetent subjects with no prior history of oral/labial or genital herpes possessed hsv-specific t cell immunity but, by multiple determinants of even the most sensitive serological assays, remained seronegative to hsv-1 and -2. of these six immune seronegative (is; hsv-seronegative with hsv-specific t cell responses) subjects, two had transien ...200312682275
crystal structure of varicella zoster virus thymidine kinase.herpes virus thymidine kinases are responsible for the activation of nucleoside antiviral drugs including (e)-5-(2-bromovinyl)-2'-deoxyuridine. such viral thymidine kinases (tk), beside having a broader substrate specificity compared with host cell enzymes, also show significant variation in nucleoside phosphorylation among themselves. we have determined the crystal structure of varicella zoster virus (vzv, human herpes virus 3) thymidine kinase complexed with (e)-5-(2-bromovinyl)-2'-deoxyuridin ...200312686543
targeted transgene integration into transgenic mouse fibroblasts carrying the full-length human aavs1 locus mediated by hsv/aav rep(+) hybrid amplicon vector.herpes simplex virus type 1/adeno-associated virus (hsv/aav) rep(+) hybrid amplicon vectors containing aav inverted terminal repeats (itrs) and rep gene sequences can mediate site-specific integration into the human genome. in this study, we have generated and characterized the first transgenic mice that bear the full-length (8.2 kb) human aavs1 locus. immortalized mouse embryonic fibroblasts from this mouse line were transduced with the rep(+), rep(-) (containing only itrs flanking the transgen ...200312923568
the inhibitory effect of essential oils on herpes simplex virus type-1 replication in vitro.the antiviral effect of 12 essential oils on herpes simplex virus type-1 (hsv-1) replication was examined in vitro. the replication ability of hsv-1 was suppressed by incubation of hsv-1 with 1% essential oils at 4 c for 24 hr. especially, lemongrass completely inhibited the viral replication even at a concentration of 0.1%, and its antiviral activity was dependent on the concentrations of the essential oil. when vero cells were treated with the essential oil before or after viral adsorption, no ...200314584615
viruses and the 26s proteasome: hacking into destruction.the discovery that the human papillomavirus e6 oncoprotein could direct the ubiquitination and degradation of the p53 tumour suppressor at the 26s proteasome was the beginning of a new view on virus-host interactions. a decade later, a plethora of viral proteins have been shown to direct host-cell proteins for proteolytic degradation. these activities are required for various aspects of the virus life-cycle from entry, through replication and enhanced cell survival, to viral release. as with onc ...200312932734
[efficacy of 4'-thio-5-ethyl-2'-deoxyuridine (tedu) and its derivatives in experimental infection in mice caused by herpes simplex virus].it was demonstrated that several 5'-phosphonates of 4'-thio-5-ethyl-2'-deoxyuridine possessed antiviral activity in vitro and in the murine model of herpes simplex virus type 1 infection. it was shown that the derivatives after intraabdominal administration penetrated effectively into the brain tissue. the agents provided statistically significant increase of the average life span, lower virus titre in the brain and lower lethality when compared to the control group of the animals. it is emphasi ...200312968461
herpesvirus entry: an update. 200312970403
development of novel selective cell ablation in the mammary gland and brain to study cell-cell interactions and chemoprevention.we have generated transgenic mice which express the gene encoding escherichia coli nitroreductase (ntr) specifically in the luminal epithelial cells of the mammary gland and the glial cells of the brain. the enzyme activates an antitumour drug cb 1954, to produce a cross-linking agent that kills all cells expressing the enzyme. we have shown that administration of the antitumour drug cb 1954 rapidly and selectively kills these cells. original experiments demonstrated the ability to ablate the lu ...200312903841
association of the herpes simplex virus type 1 us11 gene product with the cellular kinesin light-chain-related protein pat1 results in the redistribution of both polypeptides.the herpes simplex virus type 1 (hsv-1) us11 gene encodes a multifunctional double-stranded rna (dsrna)-binding protein that is expressed late in infection and packaged into the tegument layer of the virus particle. as a tegument component, us11 associates with nascent capsids after its synthesis late in the infectious cycle and is delivered into newly infected cells at times prior to the expression of viral genes. us11 is also an abundant late protein that regulates translation through its asso ...200312915535
design and synthesis of acyclic nucleoside analogs with chlorinated imidazo[1,2-a]pyridine bases.a series of acyclic c-nucleoside analogs of 2,6-dichloro- and 2,6,7-trichloroimidazo[1,2-a]pyridine were synthesized and tested for antiviral activity. the appropriate hydroxymethyl-substituted heterocycles were treated successively with thionyl chloride, an appropriate nucleophile, then diisopropylethylamine to obtain the desired acyclic nucleoside analogs. these compounds were evaluated for activity against human cytomegalovirus and herpes simplex virus, type 1. two of the dichloro analogs, bu ...200314609230
dephosphorylation of eif-2alpha mediated by the gamma(1)34.5 protein of herpes simplex virus type 1 is required for viral response to interferon but is not sufficient for efficient viral replication.the gamma(1)34.5 protein of herpes simplex virus type 1 (hsv-1) functions to block the shutoff of protein synthesis involving double-stranded rna-dependent protein kinase (pkr). in this process, the gamma(1)34.5 protein recruits cellular protein phosphatase 1 (pp1) to form a high-molecular-weight complex that dephosphorylates eif-2alpha. here we show that the gamma(1)34.5 protein is capable of mediating eif-2alpha dephosphorylation without any other viral proteins. while deletion of amino acids ...200312941928
quinine sulfate and hsv replication.although antimalarial drugs have been developed primarily to treat malaria, they are also beneficial for many dermatological, immunological, and rheumatological diseases, for which they are mostly used today in the western world. the aim of the present study was to investigate the effect of quinine sulfate (qs) on the multiplication and adsorption of herpes virus type i (hsv-1). when vero cells (african green monkey kidney) are infected with hsv-1 in the presence of qs, the viral adsorption is r ...200312952750
herpes simplex virus type 1 infection associated with atrial myxoma.some findings suggest an infectious factor in cardiac myxoma and certain histopathological features indicate herpes simplex virus type 1 (hsv-1) infection. we hypothesized that hsv-1 may be involved in the pathogenesis of cardiac myxoma. paraffin-embedded tissue samples from 17 patients with atrial myxoma were investigated for hsv-1 antigen by immunohistochemistry and viral genomic dna by nested polymerase chain reaction. the histogenesis and oncogenesis of atrial myxoma were assessed by the exp ...200314633612
increased efficacy of acyclovir-loaded microparticles against herpes simplex virus type 1 in cell culture.acyclovir is one of the most effective and selective agents against viruses of the herpes group. in order to increase its antiviral activity, acyclovir loaded microparticles, prepared by an o/w solvent evaporation method were developed. their antiviral activity against herpes simplex virus type 1 (hsv-1) and toxicity were evaluated on vero cells and then compared with those presented by a drug solution. the 50% inhibitory concentration (ic(50)) values for acyclovir loaded microspheres determined ...200312957631
cd4+cd25+ t cells regulate virus-specific primary and memory cd8+ t cell responses.naturally occurring cd4+cd25+ regulatory t cells appear important to prevent activation of autoreactive t cells. this article demonstrates that the magnitude of a cd8+ t cell-mediated immune response to an acute viral infection is also subject to control by cd4+cd25+ t regulatory cells (treg). accordingly, if natural treg were depleted with specific anti-cd25 antibody before infection with hsv, the resultant cd8+ t cell response to the immunodominant peptide ssiefarl was significantly enhanced. ...200312975455
expression of the markers bdca-2 and bdca-4 and production of interferon-alpha by plasmacytoid dendritic cells in systemic lupus erythematosus.to study the expression of blood dendritic cell antigen 2 (bdca-2) and bdca-4 molecules by plasmacytoid dendritic cells (pdcs) in the blood of patients with systemic lupus erythematosus (sle), and to study pdc production of interferon-alpha (ifn alpha) and its inhibition by anti-bdca-2 and anti-bdca-4 antibodies.200313130472
virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro.the virucidal effect of peppermint oil, the essential oil of mentha piperita, against herpes simplex virus was examined. the inhibitory activity against herpes simplex virus type 1 (hsv-1) and herpes simplex virus type 2 (hsv-2) was tested in vitro on rc-37 cells using a plaque reduction assay. the 50% inhibitory concentration (ic50) of peppermint oil for herpes simplex virus plaque formation was determined at 0.002% and 0.0008% for hsv-1 and hsv-2, respectively. peppermint oil exhibited high le ...200313678235
herpes simplex encephalitis and radiotherapy.the pathogenesis underlying the reactivation of latent herpes simplex virus remains undefined. this article presents the case of a 15-year-old male who developed herpes simplex encephalitis, as proven by a positive cerebrospinal fluid polymerase chain reaction and supported by magnetic resonance imaging findings during radiotherapy for pontine glioma. the temporal relation of radiotherapy to the occurrence of herpes simplex encephalitis suggests that cranial irradiation may play a role in the re ...200313679127
herpes simplex virus type 1 glycoprotein b sorting in hippocampal neurons.herpes simplex virus type 1 (hsv-1) is a neuroinvasive human pathogen that spreads in the nervous system in functionally connected neurons. determining how hsv-1 components are sorted in neurons is critical to elucidate the mechanisms of virus neuroinvasion. by using recombinant viruses expressing glycoprotein b (gb) tagged with green fluorescent protein (gfp), the subcellular localization of this envelope protein was visualized in infected hippocampal neurons in culture. results obtained using ...200313679595
chimeric dr fimbriae with a herpes simplex virus type 1 epitope as a model for a recombinant vaccine.the potential of the major structural protein drae of escherichia coli dr fimbriae has been used to display an 11-amino-acid peptide of glycoprotein d derived from herpes simplex virus (hsv) type 1. the heterologous sequence mimicking an epitope from glycoprotein d was inserted in one copy into the drae gene in place of a predicted 11-amino-acid sequence in the n-terminal region of surface-exposed domain 2 within the conserved disulfide loop (from cys21 to cys53). the inserted epitope was displa ...200314500468
a l.e.a.p.s. heteroconjugate vaccine containing a t cell epitope from hsv-1 glycoprotein d elicits th1 responses and protection.the l.e.a.p.s. heteroconjugate vaccine antigen (jgd), composed of a t cell epitope from glycoprotein d (gd(8-23)) of herpes simplex virus (hsv) linked with a peptide sequence from beta-2-microglobulin (aa38-50), elicited protection against lethal intraperitoneal (ip) challenge and prevented disease signs in most, and limited disease progression, for the rest of balb/c mice challenged in the epidermal abrasion-zosteriform spread mouse infection model. jgd elicited a th1 response in vaccinated mic ...200314505924
herpes simplex virus type 2 induces rapid cell death and functional impairment of murine dendritic cells in vitro.dendritic cells (dc) are critical for stimulation of naive t cells. little is known about the effect of herpes simplex virus type 2 (hsv-2) infection on dc structure or function or if the observed effects of hsv-1 on human dc are reproduced in murine dc. here, we demonstrate that by 12 h postinfection, wild-type (wt) hsv-2 (186) abortively infected murine bone marrow-derived dc and induced early cell death compared to uv-inactivated hsv-2 or mock-infected dc. hsv-2-induced loss of dc viability w ...200314512561
new antiviral drugs that target herpesvirus helicase primase enzymes.herpesviruses have infected the majority of the world's population and the associated diseases have plagued humanity since ancient times. nine causative human herpesviruses have been identified so far. the first antiviral drug was launched in 1962, and since then several drugs for treating herpesvirus infections, which work via different mechanisms, have been developed. current treatments abrogate or suppress disease symptoms but are not curative. a vaccine based on the oka strain of varicella z ...200314577954
recurrent herpes simplex labialis: selected therapeutic options.recurrent infection with herpes simplex virus 1 (hsv1), called herpes simplex labialis (hsl), is a global problem for patients with normal immune systems. an effective management program is needed for those with frequent hsl recurrences, particularly if associated morbidity and life-threatening factors are present and the patient's immune status is altered. over the past 20 years, a variety of antiviral compounds (acyclovir, penciclovir, famciclovir, valacyclovir) have been introduced that may r ...200312954137
comparison of adjuvant efficacy of herpes simplex virus type 1 recombinant viruses expressing th1 and th2 cytokine genes.the adjuvant effects of cytokines in humoral and cell-mediated immunity to herpes simplex virus type 1 (hsv-1) have been examined in mice using hsv-1 recombinant viruses expressing murine interleukin-2 (il-2), il-4, or gamma interferon (ifn-gamma) gene. groups of naive balb/c mice were immunized intraperitoneally with one or three doses of the hsv-1 recombinant viruses expressing il-2, il-4, or ifn-gamma or with parental control virus. despite similar replication kinetics, these three recombinan ...200312719570
a single amino acid substitution in the cytoplasmic tail of the glycoprotein b of herpes simplex virus 1 affects both syncytium formation and binding to intracellular heparan sulfate.herpes simplex virus 1 (hsv-1) (s) is a spontaneous syncytial mutant derived from the prototype hsv-1(f) after extensive plaque purification, and produces large syncytial plaques on vero cells. marker transfer experiments and dna sequence analysis mapped the syncytial phenotype to a t-c base substitution at codon 787 of the cytoplasmic domain of mature gb, that results in leu to pro substitution and consequently belongs to the syn 3 locus. both the cytoplasmic and the extracellular domains of gb ...200312727347
anti-herpesvirus activity of an extract of ribes nigrum l.an extract of ribes nigrum l., known as blackcurrant in europe and kurokarin(r) in japan, has been used as an ingredient in a variety of foods and folk medicine. in this study, the anti-herpesvirus activity of this extract was examined in vitro. the extract inhibited herpes simplex virus type 1 attachment on the cell membrane completely at a 100-fold dilution, as well as the plaque formation of herpes simplex virus types 1 and 2, and varicella-zoster virus by 50% at a 400-fold dilution or lower ...200312820226
association between infections and signs and symptoms of 'atopic' hypersensitivity--results of a cross-sectional survey among first-year university students in germany and spain.this study assessed the hypothesis that a decreased exposure to childhood infectious diseases is associated with signs and symptoms of 'atopic' hypersensitivity diseases.200312823114
[antiherpetic activity of l-lysine-alpha-oxidase in different dosage forms].the antiviral effect of different medicinal forms on base of l-lysin-alpha-oxidase (lo) in treatment of experimental keratits and skin diseases induced by herpes simplex virus type 1 (hsv-1) at the rabbits was examined. treatment with gel form of lo was more effective in comparison with water solution form of lo. this effect was tested by morphological, histological and immunoblotting methods in dynamics of viral disease.200312741316
identification of a novel human sand family protein in human fibroblasts induced by herpes simplex virus 1 binding.studies on interaction between herpes simplex virus 1 (hsv-1) and human fibroblasts kmb-17 have demonstrated that hsv-1 binding to the cell surface could induce a specific gene response. in this study, the hsv-1 stimulation-related gene 1 (hsrg1), a new so far unknown gene function of cellular response induced by a specific stimulation with hsv-1, was cloned from the cdna library established from mrna of early gene response of kmb-17 cells. the gene product consisted of 547 amino acids and had a ...200312828340
the stress-inducible immediate-early responsive gene iex-1 is activated in cells infected with herpes simplex virus 1, but several viral mechanisms, including 3' degradation of its rna, preclude expression of the gene.the accumulation of cellular transcripts from cells infected with herpes simplex virus 1 (hsv-1) as measured with the aid of affymetrix microchips has been reported elsewhere. among these transcripts were genes that respond to stress and that could have a noxious effect on viral replication. we have selected the stress-inducible cellular gene encoding the immediate-early response protein iex-1 to verify and determine the significance of the accumulation of these transcripts in infected cells. we ...200312743274
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