Publications

TitleAbstractYear
Filter
PMID
Filter
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
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
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
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
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
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
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
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
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
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
efficient dose-dependent and time-dependent protein transduction of pancreatic carcinoma cells in vitro and in vivo using purified vp22-egfp fusion protein.we constructed a prokaryotic vector expressing a truncated vp22-egfp gene and purified this fusion protein from escherichia coli cultures using nickel resin. application of purified vp22-egfp protein to human pancreatic carcinoma cells showed a highly efficient time-dependent and dose-dependent uptake and resulted in green fluorescence predominantly located in the nuclei of treated cells. purified vp22-egfp efficiently translocated into deeper layers of pancreatic tumor cell spheroids. homogeneo ...200312682729
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
viruses in the treatment of brain tumors.the grave outlook for malignant glioma patients in spite of improvements to current modalities has ushered in new approaches to therapy. viruses have emerged on the scene and gained attention for their ability to play essentially two roles: first, as vectors for therapeutic gene delivery and second, as engineered infectious agents capable of selectively lysing tumor cells. to date, clinical brain tumor trials using viruses for gene delivery have employed retroviral or adenoviral vectors to intro ...200212687911
correction of a rat model of parkinson's disease by coexpression of tyrosine hydroxylase and aromatic amino acid decarboxylase from a helper virus-free herpes simplex virus type 1 vector.we previously reported long-term biochemical and behavioral correction of the 6-hydroxydopamine (6-ohda) rat model of parkinson's disease (pd) by expression of tyrosine hydroxylase (th) in the partially denervated striatum, using a herpes simplex virus type 1 (hsv-1) vector. this study had a number of limitations, including the use of a helper virus packaging system, limited long-term expression, and expression of only th. to address these issues, we developed a helper virus-free packaging syste ...200312691607
[evaluation of the metabolic state and functional activity of immunocompetent cells in children with relapsing herpetic viral infection].specific features of the immune response were studied (during the clinical remission period) in 40 children (aged 3 to 6) with a relapsing herpes viral infection (rhvi). the following was established: an increased relative and absolute quantity of lymphocytes, a reduced percentage content of cd+ and an increased absolute count of cd+ in the peripheral blood. changes in the immunity humoral chain manifested themselves by an increased content of class g immunoglobulins and of circulating immune co ...200312688209
herpes simplex type i virus infection of cultured human vascular endothelial cells: expression of cell adhesion molecules and induction of interferon and cytokine production by blood mononuclear cells.the expression of cell adhesion molecules, p- and e-selectins, icam-1, and vcam-1, was studied in cultured human vascular endothelial cells (ecs) infected by herpes simplex type i virus (hsv-1). it was shown that ecs without any signs of the cytopathogenic effect (cpe) expressed on their surface p- and e-selectins as soon as 24 h after infection. no appearance of vcam-1 or increase in icam-1 expression was detected. peripheral blood mononuclear cells (pbmcs) isolated by gradient centrifugation a ...200112687235
long term antiviral suppression after treatment for neonatal herpes infection. 200312690281
analysis of the role of the membrane-spanning and cytoplasmic tail domains of herpes simplex virus type 1 glycoprotein d in membrane fusion.glycoprotein d (gd) of herpes simplex virus type 1 is a type 1 membrane protein in the virus envelope that binds to receptor molecules on the cell surface and which induces cell-cell fusion when co-expressed with gb, gh and gl. a chimeric gd molecule in which the membrane anchor and cytoplasmic tail domains were replaced with analogous regions from the human cd8 molecule was as competent as wild-type gd at mediating membrane fusion and virus entry. however, when gd was tethered to the membrane b ...200312692272
gene therapy using tissue-specific replication competent hsv.tissue- or cell-specific targeting of vectors is critical to the success of gene therapy. i describe a novel approach to viral-mediated gene therapy, where viral replication and associated cytotoxicity are limited to a specific cell-type by the regulated expression of an essential immediate-early viral gene product. this is illustrated with two herpes simplex virus type 1 vectors (g92a and d12.calp) whose growth are restricted to albumin- or calponin-expressing cells, respectively. g92a was cons ...200212703543
[herpes simplex virus type 1 and type 2]. 200312718030
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
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
[herpes simplex virus infection]. 200312722213
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
failure to genotype herpes simplex virus by real-time pcr assay and melting curve analysis due to sequence variation within probe binding sites.real-time pcr with melting curve analysis of pcr products is a rapid procedure for detecting and genotyping herpes simplex virus (hsv). when testing mucocutaneous samples for hsv by a real-time pcr assay targeting the dna polymerase gene, we found that some pcr products had atypical melting curves that did not conform to the expected melting temperatures for hsv type 1 or 2. sequence analysis showed that these strains had base-pair mismatches over the probe binding sites. an alternative assay is ...200312734260
[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
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
identification of herpes simplex virus type 1 latency-associated transcript sequences that both inhibit apoptosis and enhance the spontaneous reactivation phenotype.the herpes simplex virus type 1 (hsv-1) latency-associated transcript (lat) gene is essential for the high spontaneous and induced reactivation phenotype of hsv-1 in the rabbit ocular model and for the high induced reactivation phenotype in the mouse ocular model. recently we showed that lat has an antiapoptosis function, and we hypothesized that lat's ability to inhibit apoptosis played an important role in lat's ability to enhance the reactivation phenotype. expression of just the first 1.5 kb ...200312743314
homology modelling and docking studies on varicella zoster virus thymidine kinase.thymidine kinase (tk) is the key enzyme in antiviral and suicide gene therapies. while herpes simplex virus type 1 thymidine kinase has been widely studied and crystallised less is known on varicella zoster virus thymidine kinase (vzv tk) and its three-dimensional structure. in this paper we report the model of the three-dimensional structure of vzv tk resulting from a homology modelling study. subsequent docking studies of the natural substrate deoxythymidine (dt) and known antiviral drugs were ...200312750029
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
vaccines for viral diseases with dermatologic manifestations.vaccines against infectious diseases have been available since the 1800s, when an immunization strategy against smallpox developed by jenner gained wide acceptance. until recently, the only vaccination strategies available involved the use of protein-based, whole killed, and attenuated live virus vaccines. these strategies have led to the development of effective vaccines against a variety of diseases with primary or prominent cutaneous manifestations. effective and safe vaccines now used worldw ...200312757257
convergent synthesis of polyhalogenated quinoline c-nucleosides as potential antiviral agents.2,5,6-trichloro-1-(beta-d-ribofuranosyl)benzimidazole (tcrb) and 2-bromo-5,6-dichloro-1-(beta-d-ribofuranosyl)benzimidazole (bdcrb) are benzimidazole nucleosides that exhibit strong and selective anti-hcmv activity. we proposed to synthesize 2-halo-6,7-dichloro-4-(beta-d-ribofuranosyl)quinolines as 6 + 6 bicyclic analogues of tcrb. the synthesis used wittig reactions in two key steps. the first wittig reaction coupled a fully functionalized benzene with a ribofuranose derivative to provide (z)-6 ...200312762715
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
in vivo antiviral efficacy of a dipeptide acyclovir prodrug, val-val-acyclovir, against hsv-1 epithelial and stromal keratitis in the rabbit eye model.a dipeptide prodrug of the antiviral nucleoside acyclovir (acv), val-val-acv (vvacv), was evaluated in vivo as a potential drug candidate for improving antiviral efficacy against herpetic epithelial and stromal keratitis.200312766053
multiple determinants contribute to the virulence of hsv ocular and cns infection and identification of serine 34 of the us1 gene as an ocular disease determinant.the virulence of any given strain of herpes simplex virus (hsv) is probably due to the effects of the constellation of genes in that strain and how they act in concert to promote disease. the goal of this work was to develop a system to identify and study the role of multiple genes in hsv disease.200312766070
structure-function analysis of herpes simplex virus type 1 gd and gh-gl: clues from gdgh chimeras.in alphaherpesviruses, glycoprotein b (gb), gd, gh, and gl are essential for virus entry. a replication-competent gl-null pseudorabies virus (prv) (b. g. klupp and t. c. mettenleiter, j. virol. 73:3014-3022, 1999) was shown to express a gdgh hybrid protein that could replace gd, gh, and gl in cell-cell fusion and null virus complementation assays. to study this phenomenon in herpes simplex virus type 1 (hsv-1), we constructed four gdgh chimeras, joining the first 308 gd amino acids to various gh ...200312767993
glycoproteins m and n of human herpesvirus 8 form a complex and inhibit cell fusion.glycoproteins m (gm) and n (gn) are well conserved across the herpesvirus family and their involvement in virus penetration and egress is well described, especially for alphaherpesviruses. because there was no previous study on the homologues of human herpesvirus 8 glycoproteins m (gm8) and n (gn8), we analysed their biochemical and functional characteristics. we found that: (i) gm8 aggregated following heat treatment; (ii) gm8 was a virion component; (iii) gm8 and gn8 were n-glycosylated; (iv) ...200312771417
[study of herpes viruses in the blood of patients with cardiovascular pathology].the association between cytomegalovirus (cmv) and herpes simplex (hsv-1), on the one hand, and the coronary heart disease and chronic venous insufficiency (cvi), on the other hand, was studied; besides the infection rate by the above viruses in different age groups of donors was examined. the following methods--immune-enzyme analysis and detection of viral dna by means of the polymerase chain reaction (pcr) as well as immune-fluorescence scanning of atherosclerotic plaques--were made use in the ...200312774672
efficacy of lentivirus-mediated and muc1 antibody-targeted vp22-tk/gcv suicide gene therapy for ovarian cancer.transfer of the herpes simplex virus type 1 thymidine kinase (hsv-tk) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (gcv) exposure provides a potential gene therapy strategy for the treatment of cancer. effective gene therapy depends on the efficient transfer and specific targeting of therapeutic genes and their protein products to target cells. the purpose of this study was to investigate the anti-tumor effect of lentivirus-mediated and muc1 antibody-targeted v ...200312792977
transformation of human trabecular meshwork cells with sv40 tag alters promoter utilization.to compare promoter usage in primary differentiated and sv40 tag transformed human trabecular meshwork cells (htm and tm1 cells).200212789541
total vascular exclusion of the liver enhances the efficacy of retroviral-mediated associated thymidine kinase and interleukin-2 genes transfer against multiple hepatic tumors in rats.recent advances in gene transfer technology render gene therapy an attractive treatment of disseminated liver metastases for which other treatments remain disappointing. in this setting, total vascular exclusion of the liver could improve gene transfer to cancer cells and prevent extrahepatic vector spreading during portal infusion of therapeutic genes. we evaluate the efficiency of combined herpes simplex virus type-1 thymidine kinase (hsv1-tk) and interleukin-2 retrovirus-mediated gene transfe ...200312796736
relationship of herpes simplex virus genome configuration to productive and persistent infections.infection of susceptible cells by herpes simplex virus (hsv) can lead to productive infection or to latency, where the genomes persist in the nuclei of peripheral neurons in a quiescent state. using the hsv strain d109, which does not express any viral genes and thus establishes a quiescent state in most cells, we observed that a fraction of genomes circularized upon infection. the expression of infected cell protein (icp) 0, which is known to be involved in reactivation from latency and the pro ...200312796511
in vitro thymidine kinase/ganciclovir-based suicide gene therapy using replication defective herpes simplex virus-1 against leukemic b-cell malignancies (mcl, hcl, b-cll).a replication defective herpes simplex virus-1 was evaluated as a therapeutic vector. mantle cell lymphoma (mcl), hairy cell leukemia (hcl), and b-cell chronic lymphocytic leukemia (b-cll) were chosen because leukemic cells were collectable from peripheral bloods in these diseases. cells from six mcl, one hcl, and nine b-cll were infected in vitro with t0z.1 at 3 multiplicity of infection (moi). herpes simplex virus thymidine kinase (hsv-tk)/ganciclovir (gcv)-mediated suicide gene therapy showed ...200312801527
non-hiv antivirals - a review of the recent patent literature.this review covers the non-hiv antiviral patent literature from december 2001 to april 2002. most of the patent applications describe new compounds for the treatment of hepatitis c virus (hcv) by inhibition of the ns3 serine protease. several examples of both nucleoside and non-nucleoside inhibitors of the hcv polymerase ns5b have been reported. hepatitis b virus (hbv) therapy continues to be dominated by nucleoside analogs, but several non-nucleoside hbv polymerase inhibitors have also been rep ...200212802698
isolation of the enhanced neurovirulent hsv-1 strains from korean patients.herpes simplex virus type 1 (hsv-1) is a neurotropic dna virus which has latency in human. in this study, we isolated various hsv-1 strains, named khs, from the skin lesions of korean patients and characterized the specific features of each strain. we found that khs strains produced small, cell associated and nonsyncycial plaques in vero cells. we classified khs strains into two substrains, khs 1 which had highly condensed plaques and khs 2 which had less condensed plaques. since gd protein of h ...200312803462
the herpes simplex virus type 1 alkaline nuclease and single-stranded dna binding protein mediate strand exchange in vitro.the replication of herpes simplex virus type 1 (hsv-1) dna is associated with a high degree of homologous recombination. while cellular enzymes may take part in mediating this recombination, we present evidence for an hsv-1-encoded recombinase activity. hsv-1 alkaline nuclease, encoded by the ul12 gene, is a 5'-->3' exonuclease that shares homology with redalpha, commonly known as lambda exonuclease, an exonuclease required for homologous recombination by bacteriophage lambda. the hsv-1 single-s ...200312805441
potentiated gene delivery to tumors using herpes simplex virus/epstein-barr virus/rv tribrid amplicon vectors.the development and use of gene transfer techniques creates an opportunity to achieve better treatment modalities for numerous disease entities. promising results for treatment in tumor cells in culture and in small animal models have been reported. nevertheless, the lack of widespread vector distribution throughout tumor tissue is one of the current limitations for successful clinical application of gene therapy paradigms. the use of migratory tumor cells themselves as vector delivery vehicles ...200312804144
immune evasion by herpes simplex virus type 1, strategies for virus survival.many viruses capable of persistent or recurrent infections have evolved strategies to evade host immunity. viral evasion molecules target components of innate and acquired immunity, including complement proteins, natural killer cells, mhc class i or class ii molecules and antibody. our work focuses on hsv-1 glycoproteins gc and ge that impair antibody and complement responses. gc inhibits complement activation by binding c3b and blocking activities mediated by this pivotal complement protein, wh ...200312813914
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
gadd34 functional domains involved in growth suppression and apoptosis.gadd34 (also known as myd116) was originally described as a growth arrest and dna damage-inducible gene. increased expression of gadd34 was subsequently found to correlate with apoptosis, and forced overexpression of the protein leads to apoptosis. gadd34 protein modulates protein phosphatase type 1 activity through both direct binding to the protein, as well as through binding to other proteins that also modulate phosphatase activity. in addition, gadd34 has a region of homology with the herpes ...200312813455
a novel apoptotic interaction between hsv-1 and human corneal epithelial cells.herpes simplex virus type 1 (hsv-1) infects the cornea possibly causing blindness. the specific mechanisms of herpetic keratitis are unclear. we aimed to investigate whether hsv-1 would up- or down-regulate the apoptotic pathway of human corneal epithelial (hce) cells.200312815544
apoptosis and increased expression of fas ligand after uniocular anterior chamber (ac) inoculation of hsv-1.to determine if apoptosis occurs in the eyes and brain following uniocular anterior chamber (ac) inoculation of hsv-1 and if expression of fas ligand (fasl) or fas is altered by virus infection.200312815547
synthesis and antiherpetic activity of acyclovir phosphonates.phosphonate derivatives of acyclovir containing phosphorous acid and ethoxycarbonylphosphonic acid residues as well as their isopropyl esters were prepared. they selectively inhibited the herpes simplex virus 1 reproduction in vero cell culture, the efficacy of esters being 3-4 times higher than that of acv. the hydrolysis of the synthesized compounds was studied in the pbs buffer and human blood serum.200312816390
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
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
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
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 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
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
acute retinal necrosis following epidural steroid injections.to report a side effect of epidural corticosteroid injections for back pain.200312834695
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
[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
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
genotyping of herpes simplex virus type 1 strains isolated from ocular materials of patients with herpetic keratitis.herpes simplex virus type 1 (hsv-1) is the etiological agent of herpetic keratitis. the epithelial form ("epithelial keratitis") is attributed mainly to destruction of the epithelium through active viral replication within the epithelium. the stromal form ("stromal keratitis") is associated with immune reactions within the stroma and is the common cause of human blindness. in the present study, 29 hsv-1 strains isolated from human ocular materials of herpetic keratitis were classified into 14 ge ...200312858412
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
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
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
antiviral activity of n-benzoylphenylisoserinates of lactarius sesquiterpenoid alcohols in vitro.cytotoxic, antiviral, antibacterial and antifungal properties of a new, originally synthesised group of compounds: the n-benzoylphenylisoserinates of sesquiterpenoid alcohols - derivatives of taxol and various sesquiterpenes of lactarius origin were evaluated in vitro. among 16 compounds tested, 6 decreased hsv-1 titres. selectivity indices ranged from 13.9 to 31.7. no activity against rna viruses (parainfluenza 3, coxsackie b3, vesicular stomatitis virus, and encephalomyocarditis virus), bacter ...200312865976
[inhibition effects of rhubarb ethanol extract on herpes simplex virus infection in vivo].to know the anti-viral effects of rhubarb ethanol extract (ree) on herpes simplex virus(hsv) infection in vivo.200312870003
[evaluation on reducing effect of eye drop on herpes simplex virus-i in vitro].to observe the effect of herbal eye drop reduqing (clearing toxic heat) on herpes simplex virus (hsv) on the cytopathic effect in cell culture in vitro.200312870006
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
hsv-1 amplicon vector-mediated expression of atm cdna and correction of the ataxia-telangiectasia cellular phenotype.ataxia-telangiectasia (a-t) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, genome instability, and radiation sensitivity. previous research has shown that it is possible to correct the hereditary deficiency a-t by dna transfection in cell culture, but the large size of the atm cdna (9 kb) limits the use of many vector types for gene replacement. hsv-1 amplicon vectors provide a means to deliver large genes to cells efficiently and ...200312883528
cellular localization of nectin-1 and glycoprotein d during herpes simplex virus infection.during viral entry, herpes simplex virus (hsv) glycoprotein d (gd) interacts with a specific cellular receptor such as nectin-1 (prr1/hvec/cd111) or the herpesvirus entry mediator a (hvem/hvea). nectin-1 is involved in cell-to-cell adhesion. it is located at adherens junctions, where it bridges cells through homophilic or heterophilic interactions with other nectins. binding of hsv gd prevents nectin-1-mediated cell aggregation. since hsv gd affects the natural function of nectin-1, we further i ...200312885915
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
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
herpes simplex encephalitis. 200312892957
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
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
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
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
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
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
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
immunopathogenesis and prevention of uveitis with the behçet's disease-specific peptide linked to cholera toxin b. 200312918685
in vitro and in vivo characterization of a dual-function green fluorescent protein--hsv1-thymidine kinase reporter gene driven by the human elongation factor 1 alpha promoter.toward the goal of monitoring activity of native mammalian promoters with molecular imaging techniques, we stably transfected du145 prostate carcinoma cells with a fusion construct of enhanced green fluorescent protein (egfp) and wild-type herpes simplex virus-1 thymidine kinase (hsv1-tk) as a reporter gene driven by the promoter for human elongation factor 1 alpha (ef-1 alpha-egfp-tk). using this model system, expression of egfp was quantified by flow cytometry and fluorescence microscopy, whil ...200212920846
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
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
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
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
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
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
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
[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
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
herpesvirus entry: an update. 200312970403
Displaying items 1701 - 1800 of 2956