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characterization of soluble glycoprotein d-mediated herpes simplex virus type 1 infection.herpes simplex virus type 1 (hsv-1) entry into permissive cells involves attachment to cell-surface glycosaminoglycans (gags) and fusion of the virus envelope with the cell membrane triggered by the binding of glycoprotein d (gd) to cognate receptors. in this study, we characterized the observation that soluble forms of the gd ectodomain (sgd) can mediate entry of gd-deficient hsv-1. we examined the efficiency and receptor specificity of this activity and used sequential incubation protocols to ...200717157347
synthesis of the 5-phosphono-pent-2-en-1-yl nucleosides: a new class of antiviral acyclic nucleoside phosphonates.a new class of acyclic nucleoside phosphonates, the 5-phosphono-pent-2-en-1-yl nucleosides and their hexadecyloxypropyl esters, were synthesized from butyn-1-ol. only the hexadecyloxypropyl esters showed antiviral activity against herpes simplex virus type 1, in vitro. hexadecyloxypropyl 1-(5-phosphono-pent-2-en-1-yl)-thymine was the most active and selective compound among the synthesized nucleotides with an ec50 value of 0.90 microm.200717166725
isolation of an enhancer from the rat tyrosine hydroxylase promoter that supports long-term, neuronal-specific expression from a neurofilament promoter, in a helper virus-free hsv-1 vector system.direct gene transfer into neurons, using a virus vector, has been used to study neuronal physiology and learning, and has potential for supporting gene therapy treatments for specific neurological diseases. many of these applications require high-level, long-term recombinant gene expression, in forebrain neurons. we previously showed that addition of upstream sequences from the rat tyrosine hydroxylase (th) promoter to a neurofilament heavy gene (nf-h) promoter supports long-term expression in f ...200717169349
antiviral activity obtained from aqueous extracts of the chilean soapbark tree (quillaja saponaria molina).natural, aqueous extracts of quillaja saponaria, the chilean soapbark tree, contain several physiologically active triterpenoid saponins that display strong adjuvant activity when used in either human or animal vaccines. in this paper, we describe studies that demonstrate a novel antiviral activity of quillaja extracts against six viruses: vaccinia virus, herpes simplex virus type 1, varicella zoster virus, human immunodeficiency viruses 1 and 2 (hiv-1, hiv-2) and reovirus. we demonstrate that m ...200717170461
coexpression of interleukin-2 enhances the immunization effect of a dna vaccine expressing herpes simplex 1 glycoprotein d.in this study, dna vaccines consisting of vector ires-gd expressing herpes simplex virus 1 (hsv-1) glycoprotein d (gd) and vector ires-gd-il-2 coexpressing hsv-1 gd and interleukin-2 (il-2), respectively, were constructed. after intramuscular inoculation, both vaccines induced in balb/c mice antibodies as assayed by elisa and virus neutralization. however, ires-gd-il-2 elicited significantly higher levels of igg (elisa) and neutralizing antibodies than ires-gd. isotyping of sera from mice inject ...200617177610
n1-substituted thymine derivatives as mitochondrial thymidine kinase (tk-2) inhibitors.novel n1-substituted thymine derivatives related to 1-[(z)-4-(triphenylmethoxy)-2-butenyl]thymine have been synthesized and evaluated against thymidine kinase-2 (tk-2) and related nucleoside kinases [i.e., drosophila melanogaster deoxynucleoside kinase (dm-dnk) and herpes simplex virus type 1 thymidine kinase (hsv-1 tk)]. the thymine base has been tethered to a distal triphenylmethoxy moiety through a polymethylene chain (n = 3-8) or through a (2-ethoxy)ethyl spacer. moreover, substitutions at p ...200617181158
acute retinal necrosis features, management, and outcomes.to determine the viral diagnosis and factors affecting the visual outcome of eyes with acute retinal necrosis.200717184841
visualization of the herpes simplex virus portal in situ by cryo-electron tomography.herpes simplex virus type 1 (hsv-1), the prototypical herpesvirus, has an icosahedral nucleocapsid surrounded by a proteinaceous tegument and a lipoprotein envelope. as in tailed bacteriophages, the icosahedral symmetry of the capsid is broken at one of the 12 vertices, which is occupied by a dodecameric ring of portal protein, ul6, instead of a pentamer of the capsid protein, ul19. the portal ring serves as a conduit for dna entering and exiting the capsid. from a cryo-em reconstruction of caps ...200717188319
synthesis and antiviral activity of c-fluoro-branched cyclopropyl nucleosides.a series of novel fluorocyclopropyl nucleosides were synthesized starting from acetol using the simmons-smith reaction as a key reaction. all the nucleosides synthesized were assayed against several viruses. among the compounds synthesized, the uracil analogue 22 showed moderate anti-hcmv activity (10.61 microg/ml, in ad-169).200717188402
[genital herpes]. 200617190019
antiherpetic flavones from the heartwood of artocarpus gomezianus.the heartwood of artocarpus gomezianus was investigated for anti-herpetic principles. during the course of the separation, a new compound, artogomezianone (1), was isolated, along with the known compounds cycloartocarpin (2), isocyclomorusin (3), artocarpin (4), norcycloartocarpin (5), norartocarpetin (6), and oxyresveratrol (7). evaluation of these isolates for inhibitory effects against herpes simplex virus (hsv) types 1 and 2 was carried out using the inactivation method. compounds 2, 3, 6 an ...200617193228
[investigation of the role of ribonuclease l gene in the response of tonsil tissues against viral infections].mutations or variants that impair function of ribonuclease l (rnase-l), particularly r462q, have been proposed as susceptibility factors for the innate antiviral response. the aim of this study was to investigate and compare the expression levels of rnase-l and mutation of r462q in the tonsils of tonsillectomy patients who were infected and not infected with herpes simplex virus type 1 (hsv-1), epstein-barr virus (ebv) and human herpes virus 6 (hhv-6). six tonsils were included in the study. one ...200617205688
construction and characterization of a herpes simplex virus type i recombinant expressing green fluorescent protein: acute phase replication and reactivation in mice.a recombinant hsv-1 virus expressing egfp from the hcmv major immediate early promoter (kos-cmvgfp) was constructed to monitor viral replication and spread in vitro and in mice. kos-cmvgfp replicated as efficiently as wild-type virus, strain kos, in single cycle growth experiments in vero cells indicating that the recombinant virus has no significant growth defects in vitro. following ocular inoculation of mice, kos-cmvgfp exhibited slight but statistically significant reductions in mouse tear f ...200717207829
use of fourier transform infrared microscopy for the evaluation of drug efficiency.fourier transform infrared (ftir) spectroscopy has been used by chemists as a powerful tool to characterize inorganic and organic compounds. in this study, we examine the potential of ftir microspectroscopy for early evaluation of therapy efficiency. for this purpose, we examine the effect of acyclovir (a known antiherpetic drug) on the development of herpes simplex virus type 1 (hsv-1) infection in cell culture. also, we examine spectral changes in lymphocytes obtained from leukemia patients af ...200617212532
the infected cell protein 0 encoded by bovine herpesvirus 1 (bicp0) induces degradation of interferon response factor 3 and, consequently, inhibits beta interferon promoter activity.the icp0 protein (bicp0) encoded by bovine herpesvirus 1 is the major viral regulatory protein because it stimulates all viral promoters and, consequently, productive infection. like other icp0 analogues encoded by alphaherpesvirinae subfamily members, bicp0 contains a zinc ring finger near its amino terminus that is necessary for activating transcription, regulating subcellular localization, and inhibiting interferon-dependent transcription. in this study, we discovered that sequences near the ...200717215277
short-course therapy for recurrent genital herpes and herpes labialis. 200717217895
sialic acid on herpes simplex virus type 1 envelope glycoproteins is required for efficient infection of cells.herpes simplex virus type 1 (hsv-1) envelope proteins are posttranslationally modified by the addition of sialic acids to the termini of the glycan side chains. although gc, gd, and gh are sialylated, it is not known whether sialic acids on these envelope proteins are functionally important. digestion of sucrose gradient purified virions for 4 h with neuraminidases that remove both alpha2,3 and alpha2,6 linked sialic acids reduced titers by 1,000-fold. digestion with a alpha2,3-specific neuramin ...200717229687
maintenance of endoplasmic reticulum (er) homeostasis in herpes simplex virus type 1-infected cells through the association of a viral glycoprotein with perk, a cellular er stress sensor.in the efforts of viruses to dominate and control critical cellular pathways, viruses generate considerable intracellular stress within their hosts. in particular, the capacity of resident endoplasmic reticulum (er) chaperones to properly process the acute increase in client protein load is significantly challenged. such alterations typically induce the unfolded protein response, one component of which acts through ire1 to restore er homeostasis by expanding the folding capabilities, whereas the ...200717229688
infectious delivery and expression of a 135 kb human frda genomic dna locus complements friedreich's ataxia deficiency in human cells.friedreich's ataxia (fa) is the most common recessive ataxia, affecting 1-2 in 50,000 caucasians, and there is currently no effective cure or treatment. fa results from a deficiency of the mitochondrial protein frataxin brought about by a repeat expansion in intron 1 of the frda gene. the main areas affected are the central nervous system (particularly the spinocerebellar system) and cardiac tissue. therapies aimed at alleviating the neurological degeneration have proved unsuccessful to date. he ...200717235301
seroprevalence of herpes simplex virus types 1 and 2 in pregnant women in the united states.the purpose of this study was to determine seroprevalence of herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) in a national cross-sectional sample of pregnant women.200717240228
blocks to herpes simplex virus type 1 replication in a cell line, tsbn2, encoding a temperature-sensitive rcc1 protein.circularization of the herpes simplex virus type 1 (hsv-1) genome is thought to be an important early event during the lytic cycle. previous studies from another laboratory using a cell line, tsbn2, that carries a temperature-sensitive mutation in the gene encoding the regulator of chromatin condensation 1 (rcc1) indicated that functional rcc1 was required for hsv-1 genome circularization and subsequent viral dna synthesis. here, hsv-1 infection of tsbn2 cells has been re-examined by utilizing b ...200717251553
concurrent cmv and ebv dnaemia is significantly correlated with a delay in the response to haart in treatment-naive hiv type 1-positive patients.the purpose of this study was to assess the qualitative single and multiple herpes virus dnaemia in the peripheral blood leukocytes (pbls) of hiv-1-positive patients and its impact on the response to highly active antiretroviral therapy (haart) and immune reconstitution. all (163) hiv-1-positive patients attending "syngros aids referral center" from november 2000 to february 2001 were recruited. cmv, hsv-1, hsv-2, ebv, and hhv-8 dna were detected in pbls by polymerase chain reaction (pcr). patie ...200717263627
acute retinal necrosis.acute retinal necrosis (arn) is a rare disease that is usually caused by one of the three neurotropic human herpesviruses - herpes simplex virus type 1(hsv-1), hsv-2 and varicella-zoster virus (vzv). although much is known about the clinical course of the disease and its treatment and about the viruses that cause it, comparatively little is known about its pathogenesis. this article will review the history of arn, the typical clinical findings, and methods of diagnosis. information from studies ...200717264500
nonimmune hydrops fetalis due to herpes simplex virus type 1. 200717266163
induction of strong antitumor immunity by an hsv-2-based oncolytic virus in a murine mammary tumor model.oncolytic viruses have shown considerable promise for the treatment of solid tumors. in previous studies, we demonstrated that a novel oncolytic virus (fuson-h2), constructed by replacing the serine/threonine protein kinase (pk) domain of the icp10 gene of type 2 herpes simplex virus (hsv-2) with the gene encoding the green fluorescent protein, can selectively replicate in and thus lyse tumor cells. 4t1 tumor cells are weakly immunogenic and the mammary tumors derived from them aggressively meta ...200717266169
ctcf-dependent chromatin boundary element between the latency-associated transcript and icp0 promoters in the herpes simplex virus type 1 genome.cells latently infected with herpes simplex virus (hsv) contain nucleosomal dna similar to that of host cell chromatin. recent studies have demonstrated that histones in the latency-associated transcript (lat) promoter and intron regions contain histone modifications permissive for transcription. however, those histones associated with the lytic-specific icp0 gene, which lies only 5 kb away, contain modifications typical of silenced chromatin. how this active chromatin is kept separate from the ...200717267480
[suicidal cancer vaccine enhances anti-tumor immunotherapeutic effect and its safety in the treatment of ovarian cancer].to study the anti-tumor immunotherapeutic effect induced by the suicidalcancer vaccine fc/tk, and to evaluate the safety of this vaccine.200617274368
epithelial herpetic simplex keratitis recurrence and graft survival after corneal transplantation in patients with and without atopy.to compare the incidence of herpes simplex virus (hsv) epithelial recurrence and graft survival after penetrating keratoplasty (pk) in patients with and without self-reported atopy.200717276382
delayed but not early glucocorticoid treatment protects the host during experimental herpes simplex virus encephalitis in mice.glucocorticoids (gcs) have not been established as an evidence-based therapy for herpes simplex virus (hsv) encephalitis. we sought to evaluate the effects of early versus delayed gc administration in a model of hsv-1 encephalitis.200717299711
quantitative demonstration of intrathecal synthesis of high affinity immunoglobulin g in herpes simplex encephalitis using affinity-mediated immunoblotting.three paired serial samples of csf and serum (from days 8, 13 and 22) were taken from a patient referred to the national hospital for neurology and neurosurgery with what was duly confirmed as having herpes simplex encephalitis using pcr. the samples were investigated using affinity-mediated immunoblotting followed by incubation with sodium thiocyanate. digitisation of the blots enabled further analysis. we showed that the clones of antigen-specific igg, which were produced intrathecally, were o ...200717303253
clinical experiment of mutant herpes simplex virus hf10 therapy for cancer.we reviewed our clinical trial using mutant herpes simplex virus "hf10". we have evaluated the safety and effect of hf10 against recurrent breast cancer since 2003 and also applied hf10 to non-resectable pancreatic cancer since 2005. an oncolytic herpes simplex virus type 1, mutant hf10, has been isolated and evaluated for anti-tumor efficacy in syngeneic immunocompetent mouse models. from long time before clinical trial, we have found that the mutant virus can have remarkable potential to effec ...200717346108
modulation of microglia and cd8(+) t cell activation during the development of stress-induced herpes simplex virus type-1 encephalitis.the central nervous system (cns) has been shown to be vulnerable to a variety of insults in animals exposed to glucocorticoids. for example, psychological stress, a known inducer of glucocorticoid production, enhances the susceptibility of mice to herpes simplex virus type-1 (hsv-1) infection and results in the development of hsv-1 encephalitis (hse). to determine the immune mechanisms by which stress promotes the development of hse, we examined the role of the glucocorticoid receptor (gr) and t ...200717349776
antiviral triterpenoids from the medicinal plant schefflera heptaphylla.schefflera heptaphylla (l.) frodin is a principal ingredient of an herbal tea formulation widely used for the treatment of common cold in southern china. an extract of the long leafstalk of the compound leaf of s. heptaphylla exhibited the most potent antiviral activity against respiratory syncytial virus (rsv). further antiviral-guided fractionation and isolation of the leafstalk extract of s. heptaphylla led to obtain two highly active pure triterpenoids, namely 3alpha-hydroxylup-20(29)-ene-23 ...200717357972
selective retention of herpes simplex virus-specific t cells in latently infected human trigeminal ganglia.primary infection with herpes simplex virus 1 (hsv-1) and varicella zoster virus (vzv) results in lifelong latent infections of neurons in sensory ganglia such as the trigeminal ganglia (tg). it has been postulated that t cells retained in tg inhibit reactivation of latent virus. the acquisition of tg specimens of individuals within hours after death offered the unique opportunity to characterize the phenotype and specificity of tg-resident t cells in humans. high numbers of activated cd8(+) t c ...200717360672
combined antiherpetic effect of complex preparation "viferon-eye drops" and modified nucleosides.ready dosage form (eye drops) prepared on the basis of recombinant alpha2-ifn exhibits high activity towards herpes simplex type 1 virus in vitro. systematic study of the antiherpesvirus effect of this drug in combination with modified nucleosides showed an inhibitory effect of the synergic type. combination of ifn preparation with some nucleosides, including ribavirin, proved to be highly effective towards drug-resistant herpes virus.200617364060
effects of bicistronic lentiviral vector-mediated herpes simplex virus thymidine kinase/ganciclovir system on human lens epithelial cells.posterior capsule opacification (pco) is the most common complication after phacoemulsification cataract surgery. hyperplasia of the lens epithelial cell after phacoemulsification is thought to be an important feature contributing to pco. in this study,we investigated the feasibility of killing the human lens epithelial cells (hlecs) by lentivirus-mediated herpes simplex virus thymidine kinase (hsv-tk) gene/ganciclovir (gcv) in hlecs and studied the bystander effect. hlecs were infected with len ...200717364733
the human cytomegalovirus mhc class i homolog ul18 inhibits lir-1+ but activates lir-1- nk cells.the inhibitory leukocyte ig-like receptor 1 (lir-1, also known as ilt2, cd85j, or lilrb1) was identified by its high affinity for the human cmv (hcmv) mhc class i homolog gpul18. the role of this lir-1-gpul18 interaction in modulating nk recognition during hcmv infection has previously not been clearly defined. in this study, lir-1(+) nkl cell-mediated cytotoxicity was shown to be inhibited by transduction of targets with a replication-deficient adenovirus vector encoding ul18 (rad-ul18). fibrob ...200717372005
presence of herpes simplex virus on the oral mucosa in patients undergoing chemotherapy.the aim of this study was to confirm the presence of herpes simplex virus type 1 and 2 on the oral mucosa, in patients undergoing chemotherapy, by means of polymerase chain reaction (pcr).200717373422
role of tumor invasiveness, the extracellular matrix, and chromatin sequestration in the susceptibility of uveal melanoma to herpes simplex virus type 1.to better understand determinants of susceptibility/resistance of uveal melanomas to herpes simplex virus type 1 (hsv-1) oncolytic therapy, uveal melanoma cell lines of low (ocm1a) and of high (m619, mum2b) invasive potential were infected with hsv-1 either in the presence or absence of a laminin-rich extracellular matrix (matrigel). ocm1a cultures were destroyed faster by hsv-1 than m619 and mum2b cultures. in the presence of matrigel, all melanoma cultures demonstrated delayed destruction by h ...200717386925
molecular pet imaging of hsv1-tk reporter gene expression using [18f]feau.non-invasive imaging of transgene expression requires the appropriate combination of a reporter gene and a reporter probe. [18f]feau positron emission tomography (pet) is used for the assessment of herpes simplex virus type-1 thymidine kinase gene expression. hybrid aav phage (termed aavp) can be adapted to transduce mammalian cells by targeting to a specific receptor. we evaluated a targeted aavp vector using [18f]feau pet. this protocol describes [18f]feau production and dosing, micro-pet imag ...200717406603
a role for plasmacytoid dendritic cells in the rapid il-18-dependent activation of nk cells following hsv-1 infection.natural killer (nk) cells play a crucial role in the initial response to viral infections but the mechanisms controlling their activation are unclear. we show a rapid and transient activation of nk cells that results in the production of ifn-gamma immediately following infection with herpes simplex virus type 1 (hsv-1). activation of nk cells leading to synthesis of ifn-gamma was not mediated by a direct interaction with virus but required the presence of additional cell types and was largely de ...200717407097
antiapoptotic activity of bovine herpesvirus type-1 (bhv-1) ul14 protein.viruses have evolved different strategies to interfere with apoptotic pathways in order to halt cellular responses to infection. one previous study showed that transient transfection of bovine herpesvirus type-1 (bhv-1) ul14 protein is efficient in protecting madin darby kidney (mdbk) and human chronic myelogenous leukemia (k562) cells from sorbitol-induced apoptosis. this protein corresponds to a putative protein of bhv-1, which shares aminoacid sequence with a part of the peptide-binding domai ...200717408888
in vivo fitness and virulence of a drug-resistant herpes simplex virus 1 mutant.two important issues regarding a virus mutant that is resistant to an antiviral drug are its ability to replicate in animal hosts (in vivo fitness) relative to other genetic variants, including wild type, and its ability to cause disease. these issues have been investigated for a herpes simplex virus 1 mutant that is resistant to thiourea compounds, which inhibit encapsidation of viral dna. following corneal inoculation of mice, the mutant virus replicated very similarly to its wild-type parent ...200717412967
perineal herpes simplex infection in bedridden geriatric patients.herpes simplex virus (hsv) lesions are prone to reactivation and recurrence in response to various local or systemic triggering factors.200717428112
us3 of herpes simplex virus type 1 encodes a promiscuous protein kinase that phosphorylates and alters localization of lamin a/c in infected cells.the herpes simplex virus type 1 (hsv-1) us3 gene encodes a serine/threonine kinase that, when inactivated, causes capsids to aggregate aberrantly between the inner and outer nuclear membranes (inm and onm, respectively) within evaginations/extensions of the perinuclear space. in both hep2 cells and an engineered cell line derived from hep2 cells expressing lamin a/c fused to enhanced green fluorescent protein (egfp-lamin a/c), lamin a/c localized mostly in a reticular pattern with small regions ...200717428859
a novel double-stable t-rex/gb cell line expressing glycoprotein b of herpes simplex virus 1.we established and characterized a new stable t-rex/gb cell line expressing gb of hsv-1 under tetracycline (tet) control. the expression of complete gb (120 k) in t-rex/gb cells was detected by western blot analysis with anti-hsv-1/ang/gb monoclonal antibody as early as 2 days after tet induction. inducibility and tightness of tet-regulated gb expression in t-rex/gb cell line was shown to be preserved after long-term culture (2 months) and after numerous freezing/thawing cycles as well. in this ...200717432944
sculpting the bicyclo[3.1.0]hexane template of carbocyclic nucleosides to improve recognition by herpes thymidine kinase.the replacement of the furanose ring by a cyclopentane in nucleosides generates a group of analogues known generically as carbocyclic nucleosides. these compounds have increased chemical and enzymatic stability due to the absence of a true glycosyl bond that characterizes conventional nucleosides. the additional fusion of a cyclopropane ring to the cyclopentane produces a bicyclo[3.1.0]hexane system that depending on its location relative to the nucleobase is able to lock the embedded cyclopenta ...200717451242
aquaporin 4 regulation during acute and long-term experimental herpes simplex virus encephalitis.structural damage of the central nervous system (cns) often leads to severely disabling residual symptoms despite effective antiviral therapy during herpes simplex virus encephalitis (hsve). edematous space-occupying lesions are pathological and neuroradiological well-known phenomena for this disease. the molecular mechanisms of brain edema development in hsve are poorly understood, the regulation of water brain-blood barrier (bbb) permeability might be disturbed. aquaporin 4 (aqp4) is the predo ...200717454447
performance of focus elisa tests for hsv-1 and hsv-2 antibodies among university students with no history of genital herpes.to define the performance characteristics of the focus elisa hsv-1 and hsv-2 assay among 100 university students.200717457239
diverse herpes simplex virus type 1 thymidine kinase mutants in individual human neurons and ganglia.mutations in the thymidine kinase gene (tk) of herpes simplex virus type 1 (hsv-1) explain most cases of virus resistance to acyclovir (acv) treatment. mucocutaneous lesions of patients with acv resistance contain mixed populations of tk mutant and wild-type virus. however, it is unknown whether human ganglia also contain mixed populations since the replication of hsv tk mutants in animal neurons is impaired. here we report the detection of mutated hsv tk sequences in human ganglia. trigeminal a ...200717459924
role of anti-glycoproteins d (anti-gd) and k (anti-gk) iggs in pathology of herpes stromal keratitis in humans.to assess the relative impact of antibodies specific for hsv-1 glycoproteins on eye disease in response to hsv-1 infection, the composition of antibodies specific for 10 of the viral glycoproteins, and the effect of anti-glycoprotein (g)d and anti-gk antibodies on antibody-dependent enhancement (ade).200717460278
dual infection with polyomavirus bk and acyclovir-resistant herpes simplex virus successfully treated with cidofovir in a bone marrow transplant recipient.a hematopoietic stem cell transplant recipient developed a mucosal herpes simplex virus-1 (hsv-1) infection while under acyclovir (acv) treatment (hsv was later shown to be resistant to acv). concomitantly, the patient presented a hemorrhagic cystitis (hc) due to polyomavirus bk, for which intravenous cidofovir (cdv) was prescribed. the patient benefited from the broad-spectrum anti-dna virus activity of cdv, and not only the hc resolved without signs of nephrotoxicity but also the hsv-1 lesions ...200717461998
isolation, identification and function of a novel anti-hsv-1 protein from grifola frondosa.a novel antiviral protein was purified from an extract of grifola frondosa fruiting bodies using a procedure that included 40% ammonium sulfate precipitation and deae-cellulose ion exchange chromatography, and designated gfahp. this protein inhibited herpes simplex virus type 1 (hsv-1) replication in vitro with an ic(50) value of 4.1 microg/ml and a therapeutic index >29.3. higher concentrations of gfahp (125 and 500 microg/ml) also significantly reduced the severity of hsv-1 induced blepharitis ...200717475344
the herpes simplex virus type 1 bgkl variant, unlike the bgol variant, shows a higher association with orolabial infection than with infections at other sites, supporting the variant-dispersion-replacement hypothesis.the identification and geographic distribution of the herpes simplex virus type 1 (hsv-1) bglii restriction fragment length polymorphism (rflp) variants named bgk(l) and bgo(l) in clinical isolates from orolabial and cutaneous sites were described in our previous reports, in which the dispersion and replacement of hsv-1 variants were proposed. the base substitution sites deduced from the bgk(l) multiple rflp variations were mapped to the u(l)12 (dnase), r(l)2 (alpha0 transactivator), and latency ...200717475752
topical treatment with nerve growth factor in an animal model of herpetic keratitis.in vitro and in vivo studies demonstrated the antiviral efficacy of nerve growth factor (ngf) and its cyto-protective effect in herpes simplex virus (hsv)-infected cells. the aims of this study were to evaluate the role of endogenous ngf in hsv corneal infection, and the effects of topical ngf treatment on herpetic keratitis.200817479276
glycoprotein i of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region.glycoprotein i (gi) of herpes simplex virus type 1 (hsv-1) contains a tandem repeat (tr) region including the amino acids serine and threonine, residues that can be utilized for o-glycosylation. the length of this tr region was determined for 82 clinical hsv-1 isolates and the results revealed a polymorphic distribution of two to six or eight repeated blocks with a majority harbouring between two and four repeats. assessment of the o-glycosylation capacity of an acceptor peptide (stpstttstpsttt) ...200717485527
activation of endogenous retrovirus reverse transcriptase in multiple sclerosis patient lymphocytes by inactivated hsv-1, hhv-6 and vzv.human endogenous retroviruses (hervs) and herpesviruses have been associated with the development of multiple sclerosis (ms). these virus groups interact with each other and have been shown to induce synergistic immune responses. here, we focus on the possible role of herpesviruses as contributing factors in herv activation. we demonstrate the ability of hsv-1, hhv-6, and vzv antigens to induce higher rt activity in peripheral lymphocytes from ms patients vs. controls during the first 6 days pos ...200717493688
hsv-1 amplicon-mediated post-transcriptional inhibition of rad51 sensitizes human glioma cells to ionizing radiation.standard treatment for glioblastoma multiforme and other brain tumors consists of surgical resection followed by combined radio-/chemotherapy. however, radiation resistance of tumor cells limits the success of this treatment, and the tumors invariably recur. therefore, the selective inhibition of molecular mediators of radiation resistance may provide therapeutic benefit to the patient. one of these targets is the rad51 protein, which is a key component of the homologous recombinational repair o ...200717495946
epitope mapping of hsv-1 glycoprotein k (gk) reveals a t cell epitope located within the signal domain of gk.glycoprotein k (gk) is a virion envelope component of herpes simplex virus types 1 (hsv-1) and 2 (hsv-2), which plays an important role in virion morphogenesis and egress. we previously demonstrated that immunization of mice with gk, but not with any of the 10 other hsv-1 glycoproteins, resulted in exacerbation of corneal scarring and herpetic dermatitis following ocular hsv-1 infection. however, little is known about the gk epitope(s) that is (are) involved in t cell activities in vitro or in v ...200717499382
antigen-presenting particle technology using inactivated surface-engineered viruses: induction of immune responses against infectious agents.developments in cell-based and gene-based therapies are emerging as highly promising areas to complement pharmaceuticals, but present day approaches are too cumbersome and thereby limit their clinical usefulness. these shortcomings result in procedures that are too complex and too costly for large-scale applications. to overcome these shortcomings, we described a protein delivery system that incorporates over-expressed proteins into viral particles that are non-infectious and stable at room temp ...200717504532
effects of g207, a conditionally replication-competent oncolytic herpes simplex virus, on the developing mammalian brain.viral oncolytic therapy for malignant brain tumors involves local intratumoral delivery of a genetically engineered virus with tumor cell-specific lytic activity. promising preliminary results have been achieved in preclinical models with g207, a replication-competent herpes simplex virus type 1 constructed with multiple directed mutations. although the safety of g207 has been demonstrated in adults, application of viral oncolytic therapy to children with brain tumors has been delayed because of ...200717505980
listeria monocytogenes encephalitis mimicking herpes simplex virus encephalitis: the differential diagnostic importance of cerebrospinal fluid lactic acid levels.listeria monocytogenes is a common cause of bacterial meningitis in elderly patients and in those with impaired cellular immunity. the most common central nervous system infection caused by l. monocytogenes is acute bacterial meningitis; meningoencephalitis is uncommon and encephalitis is rare. early diagnosis of l. monocytogenes meningitis is difficult because only 50% of cerebrospinal fluid (csf) gram stains are negative. l. monocytogenes is one of the few central nervous system pathogens asso ...200717509430
[comparative study of several methods for producing experimental animal model of viral facial palsy].to select the optimal method for developing experimental animal model of viral facial paralysis by comparing several inoculation methods.200717511177
acute retinal necrosis as a late sequela of herpes simplex type 1 encephalitis in a child.herpes simplex virus (hsv) is a common infection that occasionally presents with destructive lesions. two of the most feared presentations of hsv are encephalitis and acute retinal necrosis. although there are numerous reports of acute retinal necrosis presenting after hsv-2 infection in children, it has been rarely reported in children after hsv-1 infection. herein we report a child who developed acute retinal necrosis 17 months after hsv-1 encephalitis.200717512230
two-color fluorescence analysis of individual virions determines the distribution of the copy number of proteins in herpes simplex virus particles.we present a single virion method to determine absolute distributions of copy number in the protein composition of viruses and apply it to herpes simplex virus type 1. using two-color coincidence fluorescence spectroscopy, we determine the virion-to-virion variability in copy numbers of fluorescently labeled tegument and envelope proteins relative to a capsid protein by analyzing fluorescence intensity ratios for ensembles of individual dual-labeled virions and fitting the resulting histogram of ...200717513380
virus inactivation by protein denaturants used in affinity chromatography.virus inactivation by a number of protein denaturants commonly used in gel affinity chromatography for protein elution and gel recycling has been investigated. the enveloped viruses sindbis, herpes simplex-1 and vaccinia, and the non-enveloped virus polio-1 were effectively inactivated by 0.5 m sodium hydroxide, 6 m guanidinium thiocyanate, 8 m urea and 70% ethanol. however, ph 2.6, 3 m sodium thiocyanate, 6 m guanidinium chloride and 20% ethanol, while effectively inactivating the enveloped vir ...200717517521
a herpes simplex virus gd-yfp fusion glycoprotein is transported separately from viral capsids in neuronal axons.two models describing how alphaherpesviruses exit neurons differ with respect to whether nucleocapsids and envelope glycoproteins travel toward axon termini separately or as assembled enveloped virions. recently, a pseudorabies virus glycoprotein d (gd)-green fluorescent protein fusion was found to colocalize with viral capsids, supporting anterograde transport of enveloped virions. previous antibody staining experiments demonstrated that herpes simplex virus (hsv) glycoproteins and capsids are ...200717522199
synthesis of neutral and cationic tripyridylporphyrin-d-galactose conjugates and the photoinactivation of hsv-1.neutral and cationic tripyridylporphyrin-d-galactose conjugates were synthesized and their antiviral activity against herpes simplex virus type 1 (hsv-1) was evaluated. at non-cytotoxic concentrations the studied compounds show significant antiviral activity after photoactivation. the influence of photoactivation on drug treated cells was also analyzed, at different times of infection with hsv-1, for a neutral (1b) and a cationic glycoporphyrin (3b) derivative. the results show that the inhibiti ...200717524654
adenoviral gene transfer in bovine adrenomedullary and murine pheochromocytoma cells: potential clinical and therapeutic relevance.recombinant adenoviruses (rad) have been widely used as gene transfer vectors both in the laboratory and in human clinical trials. in the present study, we investigated the effects of adenoviral-mediated gene transfer in primary bovine adrenal chromaffin cells (bacc) and a murine pheochromocytoma cell line (mpc). cells were infected with one of three nonreplicating e1/e3-deleted (e1(-)/e3(-)) rad vectors: ad.gfp, expressing a green fluorescent protein (gfp); ad.null, expressing no transgene; or ...200717525127
ménétrier's disease associated with herpes infection: response to treatment with acyclovir. 200717531647
herpes simplex virus type-1 meningoencephalitis showing disseminated cortical lesions.we report a 41-year-old man with meningoencephalitis associated with herpes simplex virus type 1 (hsv-1). the patient developed fever, headache and dysuria followed by generalized convulsion and neck stiffness, and the csf showed pleocytosis. the titers of enzyme-linked immunosorbent assay against hsv measured 6 days after onset showed a significant rise; igg antibody 4.89 (<0.2) and igm antibody 1.45 (<0.8) in csf, igg antibody 46.1 (<2.0) and igm antibody 1.76 (<0.8) in the serum. the antibody ...200717541231
herpes simplex virus glycoproteins gb and gh function in fusion between the virion envelope and the outer nuclear membrane.herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm and, ultimately, to exit cells. it is believed that herpesvirus nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane (nm). to reach the cytoplasm these enveloped particles must fuse with the outer nm and the unenveloped capsids then acquire a second envelope in the trans-golgi network. little is known about the process by which herpesviruses virions fuse with the outer nm. here we ...200717548810
a mutation in the human herpes simplex virus type 1 ul52 zinc finger motif results in defective primase activity but can recruit viral polymerase and support viral replication efficiently.herpes simplex virus type 1 (hsv-1) encodes a heterotrimeric helicase/primase complex consisting of ul5, ul8, and ul52. ul5 contains conserved helicase motifs, while ul52 contains conserved primase motifs, including a zinc finger motif. although hsv-1 and hsv-2 ul52s contain a leucine residue at position 986, most other herpesvirus primase homologues contain a phenylalanine at this position. we constructed an hsv-1 ul52 l986f mutation and found that it can complement a ul52 null virus more effic ...200717553899
susceptibility of cancer cells to herpes simplex virus-dependent apoptosis.apoptosis has recently been associated with herpes simplex virus 1 (hsv-1) latency and disease severity. there is an intricate balance between pro- and anti-apoptotic processes during hsv-1 infection. when anti-apoptotic pathways are suppressed, this balance is upset and the cells die by apoptosis, referred to here as hsv-1-dependent apoptosis (hdap). it has been observed previously that hela cancer cells exhibit an enhanced sensitivity to hdap. here, a series of specific patient-derived cancer ...200717554017
treatment of inflamed pancreas with enkephalin encoding hsv-1 recombinant vector reduces inflammatory damage and behavioral sequelae.this study assessed the efficacy of pancreatic surface delivered enkephalin (enk)-encoding herpes simplex virus type 1 (hsv-1) on spontaneous behaviors and spinal cord and pancreatic enkephalin expression in an experimental pancreatitis model. replication-defective hsv-1 with proenkephalin complementary dna (cdna) (hsv-enk) or control beta-galactosidase cdna (hsv-beta-gal), or media vehicle (veh) was applied to the pancreatic surface of rats with dibutyltin dichloride (dbtc)-induced pancreatitis ...200717565349
neuroimaging of herpesvirus infections in children.six members of the herpesvirus family cause well-described neurologic disease in children: herpes simplex virus-1 (hsv-1), herpes simplex virus-2 (hsv-2), varicella-zoster (vzv), epstein-barr (ebv), cytomegalovirus (cmv), and human herpes virus-6 (hhv-6). when herpesviruses infect the central nervous system (cns), the clinical presentation is non-specific and often confounding. the clinical urgency is often underscored by progressive neurologic deficits, seizures, or even death, and prompt diagn ...200717572889
enzymatic therapeutic index of acyclovir. viral versus human polymerase gamma specificity.we have examined the kinetics of incorporation of acyclovir triphosphate by the herpes simplex virus-1 dna polymerase holoenzyme (pol-ul42) and the human mitochondrial dna polymerase using transient kinetic methods. for each enzyme, we compared the kinetic parameters for acyclovir to those governing incorporation of dgtp. the favorable ground state dissociation constant (6 microm) and rate of polymerization (10 s(-1)) afford efficient incorporation of acyclovir triphosphate by the pol-ul42 enzym ...200717573351
asymptomatic shedding of hsv-1 in patients undergoing oral surgical procedures and attending for noninvasive treatment.oral surgery and stress can trigger and/or increase asymptomatic shedding of herpes simplex virus type-1 (hsv-1) into human saliva. in this investigation we examined the frequency of hsv-1 shedding in 32 patients undergoing an oral surgery procedure compared with 40 control patients attending for noninvasive treatment. control patients comprised 18 migraine patients and 22 patients with temporomandibular (tmd) joint problems. nested-pcr was carried out on oral rinses collected from each patient ...200717577329
psychological stress compromises cd8+ t cell control of latent herpes simplex virus type 1 infections.recurrent hsv-1 ocular disease results from reactivation of latent virus in trigeminal ganglia, often following immunosuppression or exposure to a variety of psychological or physical stressors. hsv-specific cd8+ t cells can block hsv-1 reactivation from latency in ex vivo trigeminal ganglia cultures through production of ifn-gamma. in this study, we establish that either cd8+ t cell depletion or exposure to restraint stress permit hsv-1 to transiently escape from latency in vivo. restraint stre ...200717579052
effect of temperature, medium composition, and cell passage on production of herpes-based viral vectors.our work uses replication-defective genomic herpes simplex virus type-1 (hsv-1)-based vectors to transfer therapeutic genes into cells of the central nervous system and other tissues. obtaining highly purified high-titer vector stocks is one of the major obstacles remaining in the use of these vectors in gene therapy applications. we have examined the effects of temperature and media conditions on the half-life of hsv-1 vectors. the results reveal that hsv stability is 2.5-fold greater at 33 deg ...200217590937
type i interferon subtypes produced by human peripheral mononuclear cells from one normal donor stimulated by viral and non-viral inducing factors.through the activation of toll-like receptors (tlrs) or cytosolic rna helicases, a large number of pathogenic or synthetic components can induce the transcription of genes coding for type i interferons (ifns). this family of related cytokines includes notably, a single ifn-beta protein and 13 different ifn-alpha subtypes, whose biological activities are probably not the same. the aim of this study was to characterize the type i ifn subtypes produced in vitro by human peripheral blood mononuclear ...200717594944
evaluation of antiviral activity of south american plant extracts against herpes simplex virus type 1 and rabies virus.this paper describes the screening of different south american plant extracts and fractions. aqueous and organic extracts were prepared and tested for antiherpetic (hsv-1, kos and 29r strains) and antirabies (pv strain) activities. the evaluation of the potential antiviral activity of these extracts was performed by using an mtt assay for hsv-1, and by a viral cytopathic effect (cpe) inhibitory method for rabies virus (rv). the results were expressed as 50% cytotoxicity (cc(50)) for mtt assay an ...200717604374
oral topical cidofovir: novel route of drug delivery in a severely immunosuppressed patient with refractory multidrug-resistant herpes simplex virus infection.we present a case of serious treatment-refractory acyclovir- and foscarnet-resistant herpes simplex virus (hsv) type-1 orolingual infection that responded to oral cidofovir rinses after failure of acyclovir and foscarnet therapy. the use of 3% cidofovir in a saline rinse for refractory mucosal hsv infection appears promising but needs prospective evaluation.200717605730
treatment of herpes simplex virus infection: rationale for occlusion.orofacial herpes is a widespread benign malady that is also commonly known as herpes labialis or cold sores. herpes of this type is generally caused by herpes simplex virus type 1 (hsv-1) and, to a lesser degree, herpes simplex virus type 2 (hsv-2), both of which are dna viruses. the clinical presentation of herpetic lesions is normally located on mucocutaneous areas of the face and may eventually erode and ulcerate, leaving wounds that are known to be difficult to successfully treat. focus of t ...200717620742
the cysteine protease inhibitors cystatins inhibit herpes simplex virus type 1-induced apoptosis and virus yield in hep-2 cells.the role of cystatins in herpes simplex virus (hsv)-induced apoptosis and viral replication has been studied. human epithelial (hep-2) cells infected with wild-type hsv-1 (f), with a deletion virus lacking the anti-apoptotic gene us3 (r7041) or with a deletion virus lacking the anti-apoptotic genes us3 and icp4 (d120) were treated with cystatin a, c or d. cells and culture media were studied at different time points for replicating hsv-1 and for apoptosis. cystatins c and d inhibited the yield o ...200717622610
structural features and antiviral activity of sulphated fucans from the brown seaweed cystoseira indica.natural compounds offer interesting pharmacological perspectives for antiviral drug development. in this study, we have analysed sulphated-fucan-containing fractions isolated from the brown seaweed cystoseira indica. the crude water extract (ciwe) and the main fraction (cif3) obtained by anion exchange chromatography had potent antiviral activity against herpes simplex virus types 1 (hsv-1) and 2 (hsv-2) without cytotoxicity for vero cell cultures. furthermore, they had no direct inactivating ef ...200717626599
herpes simplex virus type 1 c-terminal variants of the origin binding protein (obp), obpc-1 and obpc-2, cooperatively regulate viral dna levels in vitro, and obpc-2 affects mortality in mice.two in-frame, c-terminal isoforms of the herpes simplex virus type 1 (hsv-1) origin binding protein (obp), obpc-1 and obpc-2, and a unique c-terminal transcript, ul8.5, are specified by hsv-1 dna. as the first isoform identified, obpc-1 was initially assumed to be the product of the ul8.5 transcript. recent evidence has demonstrated, however, that obpc-1 is a cathepsin b-mediated cleavage product of obp, suggesting that obpc-2 is the product of the ul8.5 transcript. because both obpc-1 and -2 co ...200717634223
genital co-infection with herpes simplex viruses type 1 and 2: comparison of real-time pcr assay and traditional viral isolation methods.we report the clinical case of a genital outbreak with both herpes simplex type 1 (hsv-1) and herpes simplex type 2 (hsv-2) during pregnancy. herpes was presumptively identified by clinical presentation of lesion and tzanck smear while serotypes were identified by cell culture and polymerase chain reaction (pcr). this case report highlights the need for increased surveillance of both serotypes in genital infection of pregnant women for effective disease management and reduced risk of transmissio ...200717635649
on the influence of neutrophils in corneas with necrotizing hsv-1 keratitis following amniotic membrane transplantation.necrotizing herpetic stromal keratitis (hsk) in mice rapidly improved after amniotic membrane transplantation (amt). in this study we determined the fate of polymorphonuclear neutrophils (pmn) after amt. amt or tarsorrhaphy (t) was performed in balb/c mice with ulcerative hsk. after 2 days, corneas were studied histologically and by transmission electron microscopy (tem). cd11b, gr-1, and tunel-positive cells were identified. macrophages were depleted by subconjunctival injection of dichlorometh ...200717637463
an importin alpha/beta-recognized bipartite nuclear localization signal mediates targeting of the human herpes simplex virus type 1 dna polymerase catalytic subunit pul30 to the nucleus.although the 1235 amino acids human herpes simplex virus type 1 (hsv-1) dna polymerase catalytic subunit, pul30, is essential for hsv-1 replication in the nucleus of host cells, little information is available regarding its nuclear import mechanism. the present study addresses this issue directly, characterizing pul30's nuclear import pathway for the first time using quantitative confocal laser scanning microscopy (clsm) on living cells, and fluorescent binding assays. in addition to a previousl ...200717640102
emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both ul34 and us3.cells infected with wild-type herpes simplex virus type 1 (hsv-1) show disruption of the organization of the nuclear lamina that underlies the nuclear envelope. this disruption is reflected in changes in the localization and phosphorylation of lamin proteins. here, we show that hsv-1 infection causes relocalization of the lem domain protein emerin. in cells infected with wild-type virus, emerin becomes more mobile in the nuclear membrane, and in cells infected with viruses that fail to express u ...200717652388
characterization of ebv gb indicates properties of both class i and class ii viral fusion proteins.to gain insight into epstein-barr virus (ebv) glycoprotein b (gb), recombinant, secreted variants were generated. the role of putative transmembrane regions, the proteolytic processing and the oligomerization state of the gb variants were investigated. constructs containing 2 of 3 c-terminal hydrophobic regions were secreted, indicating that these do not act as transmembrane anchors. the efficiency of cleavage of the gb furin site was found to depend on the nature of c-terminus. all of the gb co ...200717655906
hippomanin a from acetone extract of phyllanthus urinaria inhibited hsv-2 but not hsv-1 infection in vitro.phyllanthus urinaria linnea (euphorbiaceae) is a commonly used traditional medicinal plant in oriental countries and has been reported to possess various biological activities. previously, the acetone extract and some pure compounds from p. urinaria were found to suppress herpes simplex virus (hsv). in this study, another two pure compounds were isolated from acetone extract of p. urinaria and were tested for their in vitro anti-hsv-1 and hsv-2 activities. the results showed that hippomanin a im ...200717661333
neuronal apoptosis in herpes simplex virus - 1 encephalitis (hse).herpes simplex virus infections are encountered often due to their ubiquitous nature. common sites involved include skin, mucous membrane, genitalia, eye and the nervous system. hsv infection of the central nervous system can be life threatening. little is known about the pathogenesis of this cataclysmic disease, at the cellular level. virus induced apoptosis may play a role in the molecular pathogenesis of encephalitis. this study aims to detect the presence of apoptosis: a) in the brain tissue ...200117664814
complexes between herpes simplex virus glycoproteins gd, gb, and gh detected in cells by complementation of split enhanced green fluorescent protein.the interactions between herpes simplex virus gd and its nectin1 receptor or between gd, gb, and gh were analyzed by complementation of the n and c portions of split enhanced green fluorescent protein (egfp) fused to the glycoproteins. the gd(n)-nect(c) complex was readily detected; the gd(n)-gc(c) complex was undetectable, highlighting the specificity of the assay. split egfp complementation was detected between proteins designated gd(n)+gh(c), gd(n)+gb(c), and gh(n)+gb(c)+wtgd (gb was deleted ...200717670828
acute oral ulcers. 200717670868
an s/mar-based infectious episomal genomic dna expression vector provides long-term regulated functional complementation of ldlr deficiency.episomal gene expression vectors offer a safe and attractive alternative to integrating vectors. here we describe the development of a high capacity episomal vector system exploiting human episomal retention sequences to provide efficient vector maintenance and regulated gene expression through the delivery of a genomic dna locus. the ibac-s/mar vector is capable of the infectious delivery and retention of large genomic dna transgenes by exploiting the high transgene capacity of herpes simplex v ...200717675302
an hsv vector system for selection of ligand-gated ion channel modulators.pathological alterations of ion channel activity result from changes in modulatory mechanisms governing receptor biology. here we describe a conditional herpes simplex virus (hsv) replication-based strategy to discover channel modulators whereby inhibition of agonist-induced channel activation by a vector-expressed modulatory gene product prevents ion flux, osmotic shock and cell death. inhibition of channel activity, in this case, the rat vanilloid (trpv1 or the glycine receptor (glyralpha1), c ...200717676048
intracellular trafficking and maturation of herpes simplex virus type 1 gb and virus egress require functional biogenesis of multivesicular bodies.the biogenesis of multivesicular bodies (mvbs) is topologically equivalent to virion budding. hence, a number of viruses exploit the mvb pathway to build their envelope and exit from the cell. by expression of dominant negative forms of vps4 and vps24, two components of the mvb pathway, we observed an impairment in infectious herpes simplex virus (hsv) assembly/egress, in agreement with a recent report showing the involvement in hsv envelopment of vps4, the mvb-specific atpase (c. m. crump, c. y ...200717686835
search for evidence of recurring or persistent viruses in crohn's disease.new-onset crohn's disease and acute flares are often associated with viral infections. the aim of this study was to search for evidence of persistent or recurrent viruses in patients. tissue blocks were obtained from surgical specimens from patients and a control population. 111 samples were tested by pcr or rt-pcr, for ebv, cmv, hsv 1, hsv 2, hhv 8, pestiviruses, and enteroviruses. additionally, seven sets of serum samples, including pre-operative and post-operative samples, from cd patients we ...200717696953
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