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hunting for ion channel modulators with herpes simplex virus. 200717762875
role of 3-o-sulfated heparan sulfate in virus-induced polykaryocyte formation.one way herpes simplex virus type-1 (hsv-1) spreads in vivo is by polykaryocytes formation. here we demonstrate that polykaryocyte production during hsv-1 spread in cultured human corneal fibroblasts (cf) required heparan sulfate (hs) and more specifically 3-o sulfated hs (3-os hs). the polykaryocyte formation heavily depended on the expression of hs on target (cf) cells but not on glycoprotein expressing effector cells. furthermore, we provide the first visual evidence of 3-os hs and hsv-1 gd c ...200717765228
systemic delivery of (gamma1)34.5-deleted herpes simplex virus-1 selectively targets and treats distant human xenograft tumors that express high mek activity.deltagamma(1)34.5 mutant herpes simplex type 1 viruses are under active clinical investigation as oncolytic therapy for cancer. mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (mek) activity has been shown to suppress protein kinase r and thereby confer oncolytic susceptibility to some human tumors by r3616, a virus deleted for both copies of gamma(1)34.5. we report that systemic delivery of r3616 can selectively target and destroy human xenograft tumors that overex ...200717804745
lentiviral vector conferring resistance to mycophenolate mofetil and sensitivity to ganciclovir for in vivo t-cell selection.several clinical studies of gene-modified t cells have shown limited in vivo function of the cells, immunogenicity of the transgene, and lack of a selective advantage for gene-modified t cells. to address these problems, we developed a lentiviral vector (lv) that provides a selectable, proliferative advantage and potentially decreases immunogenicity for transduced t cells. the bicistronic vector expressed two genes linked with an internal ribosomal entry site. one gene is a variant of the inosin ...200717805303
susceptibility to hsv-1 infection and exercise stress in female mice: role of estrogen.exhaustive exercise has been associated with an increased risk for upper respiratory tract infections in mice and humans. we have previously shown (brown as, davis jm, murphy ae, carmichael md, ghaffer a, mayer ep. med sci sports exerc 36: 1290-1295, 2004) that female mice are better protected from the lethal effects of herpes simplex virus type 1 (hsv-1) infection, both at rest and following exercise stress, but little is known about possible mechanisms. this study tested the effects of estroge ...200717823297
development of an aciclovir implant for the effective long-term control of herpes simplex virus type-1 infection in vero cells and in experimentally infected skh-1 mice.human herpes simplex virus type-1 (hsv-1) is treatable with oral doses of an antiviral agent such as aciclovir (acv), a drug that has poor bioavailability. an alternative for delivering acv would employ a long-lived subcutaneous implant that would allow for near zero-order drug delivery kinetics. this study aimed to develop an implant composed of a matrix of silicone and acv that is capable of sustained long-term release of acv. once the implants had been created, release of acv from the implant ...200717851051
an oncolytic mutant of herpes simplex virus type-1 in which replication is governed by a promoter/enhancer of human papillomavirus type-16.although herpes simplex virus type-1 (hsv-1) can be used as an oncolytic virus it has the undesirable side effect of neurotoxicity. to create a virus with improved specificity for oral cancer we used a fragment of human papillomavirus type-16, which is frequently found in oral and cervical cancers, but not elsewhere. the upstream regulatory region, urr16, was shown to have a high level of transcriptional activity in three of four oral cancer cell lines but low activity in three cell lines derive ...200717853922
the varicella-zoster virus dna encapsidation genes: identification and characterization of the putative terminase subunits.the putative dna encapsidation genes encoded by open reading frames (orfs) 25, 26, 30, 34, 43, 45/42 and 54 were cloned from varicella-zoster virus (vzv) strain ellen. sequencing revealed that the ellen orfs were highly conserved at the amino acid level when compared to those of 19 previously published vzv isolates. additionally, rt-pcr provided the first evidence that orf45/42 was expressed as a spliced transcript in vzv-infected cells. all seven orfs were expressed in vitro and full length pro ...200717868947
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
effect of promoter strength on protein expression and immunogenicity of an hsv-1 amplicon vector encoding hiv-1 gag.helper-free herpes simplex virus type-1 (hsv-1) amplicon vectors elicit robust immune responses to encoded proteins, including human immunodeficiency virus type-1 (hiv-1) antigens. to improve this vaccine delivery system, seven amplicon vectors were constructed, each encoding hiv-1 gag under the control of a different promoter. gag expression levels were analyzed in murine and human cell lines, as well as in biopsied tissue samples from injected mice; these data were then compared with gag-speci ...200717145123
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
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
normal brain cells contribute to the bystander effect in suicide gene therapy of malignant glioma.lentiviral vectors pseudotyped with glycoproteins of the lymphocytic choriomeningitis virus (lcmv-gp) are promising candidates for gene therapy of malignant glioma, as they specifically and efficiently transduce glioma cells in vitro and in vivo. here, we evaluated the therapeutic efficacy of lcmv-gp and vesicular stomatitis virus glycoprotein (vsv-g) pseudotyped vectors.200718006778
effect of genital ulcer disease on hiv-1 coreceptor expression in the female genital tract.to examine the expression of human immunodeficiency virus type 1 (hiv-1) coreceptors (ccr5 and cxcr4) by monocytic cells within human genital ulcers.200718008231
sln as a topical delivery system for artemisia arborescens essential oil: in vitro antiviral activity and skin permeation study.the effect of sln incorporation on transdermal delivery and in vitro antiherpetic activity of artemisia arborescens essential oil was investigated. two different sln formulations were prepared using the hot-pressure homogenization technique, compritol 888 ato as lipid, and poloxamer 188 and miranol ultra c32 as surfactants. formulations were examined for their stability for two years by monitoring average size distribution and zeta potential values. the antiviral activity of free and sln incorpo ...200718019840
[radiograph patterns in herpes simples virus i pneumonia in the adult].the aim of this study is to describe epidemiology, patogénesis, pulmonary manifestations and rx findings in adult patients with varicella pneumonia (vp). four patients were studied. the diagnosis was established by clinical and radiologic criteria. all had fever , esanthem, 3 cough, 2 dyspnea. chest x-ray showed interstitial micronodular pattern at bases. 1 case developed airspace consolidation by staphylococcus aureus. 2 were admitted to icu. the four received iv acyclovir. we concluded that ad ...200718020880
infection of human endothelium in vitro by cytomegalovirus causes enhanced expression of purinergic receptors: a potential virus escape mechanism?human cytomegalovirus (cmv) uses different strategies to escape from human host defense reactions. previously we have observed that infection of endothelial cells with cmv in vitro leads to enhanced activity of endothelial ectonucleotidases. these ectoenzymes are responsible for hydrolysis of extracellular adenine nucleotides, resulting in the formation of adenosine. infection with cmv in vivo therefore may result in local increase of adenosine production, providing an anti-inflammatory and anti ...200718049120
intercellular trafficking of vp22, a herpes simplex virus type 1 tegument protein.the herpes simplex virus type 1 (hsv-1) tegument protein, vp22 has been reported to have the property of intercellular transport. the previous studies have shown that following expression of a fusion protein containing vp22; it spreads to every cell in a monolayer and concentrates in the nucleus. in spite of these reports, some studies have shown that vp22 trafficking and its nucleus accumulation is an artifact and no improvement in translocation of proteins fused to vp22 has been detected.200718051705
synthesis and evaluation of cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[(124)i]iodouracil: a new potential pet imaging agent for hsv1-tk expression.in our pursuit to find an appropriate reporter probe for herpes simplex virus type-1 thymidine kinase (hsv1-tk), a carbocyclic nucleoside analogue, cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[124i]iodouracil, has been efficiently synthesized. a pd(0)-catalyzed coupling reaction together with organotin and exchange reactions for radiolabeling gave more than 80% radiochemical yield with greater than 95% radiochemical purity and 1.15 gbq/mumol specific activity. biological data reveal that the ...200717960926
role of af6 protein in cell-to-cell spread of herpes simplex virus 1.af6 and its rat homologue afadin are multidomain proteins localized at cell junctions and involved in intercellular adhesion. af6 interacts via its pdz domain with nectin-1 at epithelial adherens junctions. nectin-1 serves as a mediator of cell-to-cell spread for herpes simplex virus 1 (hsv-1). we analyzed the role of af6 protein in the viral spread and nectin-1 clustering at cell-cell contacts by knockdown of af6 in epithelial cells. af6 knockdown reduced efficiency of hsv-1 spreading, however, ...200717967423
three consecutive episodes of acute retinal necrosis due to herpes simplex-1 over twelve years following herpetic encephalitis.to report a case of multiple delayed recurrence of acute retinal necrosis syndrome occurring in the same eye following initial herpetic encephalitis.200717972228
biophysical investigation of human heparan sulfate d-glucosaminyl 3-o-sulfotransferase-3a: a mutual effect of enzyme oligomerisation and glycosaminoglycan ligand binding.3-o-sulfation of heparan sulfate (hs) is the rarest modification within heparan sulfate biosynthesis resulting in unique biological activities. heparan sulfate d-glucosaminyl 3-o-sulfotransferase-3a (3-ost-3a) (ec 2.8.2.23) generates a binding site for the envelope glycoprotein d (gd) of herpes simplex virus 1. we have expressed the sulfotransferase domain of the human heparan sulfate 3-ost-3a isoform in escherichia coli and subsequently purified the active enzyme which was found to be present a ...200717936096
direct interaction between the n- and c-terminal portions of the herpes simplex virus type 1 origin binding protein ul9 implies the formation of a head-to-tail dimer.ul9, a superfamily ii helicase, is a multifunctional protein required for herpes simplex virus type 1 replication in vivo. although the c-terminal 317-amino-acid dna binding domain of ul9 exists as a monomer, the full-length protein behaves as a dimer in solution. thus, it has been assumed that the n-terminal 534 residues contain a region necessary for efficient dimerization and that ul9 dimers are in a head-to-head configuration. we recently showed, however, that residues in the n terminus coul ...200717942532
human herpes simplex labialis.humans are the natural host for eight of more than 80 known herpes viruses. infections with herpes simplex virus type 1 (hsv-1) are ubiquitous worldwide and highly transmissible. herpes simplex labialis (hsl) is the best-recognized recrudescent infection of the lips and perioral tissues caused by hsv-1. facial lesions of hsl may be unsightly, frequent outbreaks unpleasant, and the infection itself more severe locally and systemically in immunocompromised people. this article highlights the patho ...200717953630
the impact of dental surgery on hsv-1 reactivation in the oral mucosa of seropositive patients.herpes simplex virus type 1 (hsv-1) is a member of the human herpes virus family. most of the population (90%) has antibodies to hsv-1, and as many as 40% of these individuals may develop secondary herpes. shedding of hsv-1 in the oral mucosa can be induced by many factors, including stress, sunlight, menstruation, and physical trauma. the aim of the present study was to evaluate the impact of dental surgical procedures on hsv-1 shedding in the oral mucosa.200717954324
hiv-1/hsv-2 co-infected adults in early hiv-1 infection have elevated cd4+ t cell counts.hiv-1 is often acquired in the presence of pre-existing co-infections, such as herpes simplex virus 2 (hsv-2). we examined the impact of hsv-2 status at the time of hiv-1 acquisition for its impact on subsequent clinical course, and total cd4+ t cell phenotypes.200717957262
epidemiology of orofacial herpes simplex virus infections in the general population in france: results of the herpimax study.prevalence of clinically manifest orofacial herpes in the general population is poorly characterized. objectives to establish the lifetime prevalence of clinically manifest orofacial herpes and its relationship with herpes simplex virus (hsv) serotype in the french general population.200717958848
murine gammaherpesvirus 68 serum antibodies in general human population.previous studies using elisa and virus neutralization test (vnt) have proved the presence of murine gammaherpesvirus 68 (mhv-68) serum antibodies in sera of laboratory staff working with mhv-68, as well as in the general population. in this study, we investigated the incidence of serum antibodies to mhv-68 and to human herpesviruses presumably antigenically similar to mhv-68, as herpes simplex virus 1 (hsv-1), human cytomegalovirus (hcmv), and epstein-barr virus (ebv), in general population usin ...200718197737
peripheral herpes simplex keratitis following lasik. 200717985792
genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans.herpes simplex encephalitis is a rare complication of herpes simplex virus 1 infection that strikes otherwise healthy individuals. its pathogenesis has long remained elusive. we highlight the investigations dealing with the genetic basis of herpes simplex encephalitis in mice and humans.200717989525
systemic therapy of spontaneous prostate cancer in transgenic mice with oncolytic herpes simplex viruses.oncolytic viruses are an innovative therapeutic strategy for cancer, wherein viral replication and cytotoxicity are selective for tumor cells. here we show the efficacy of systemically administered oncolytic viruses for the treatment of spontaneously arising tumors, specifically the use of oncolytic herpes simplex viruses (hsv) administered i.v. to treat spontaneously developing primary and metastatic prostate cancer in the transgenic tramp mouse, which recapitulates human prostate cancer progre ...200717909046
antiviral activity of esterified alpha-lactalbumin and beta-lactoglobulin against herpes simplex virus type 1. comparison with the effect of acyclovir and l-polylysines.the antiviral activity of methylated alpha-lactalbumin (met-ala), methylated and ethylated beta-lactoglobulins (met- and et-blg) was evaluated against acyclovir (acv)-sensitive and -resistant strains of herpes simplex virus type 1 (hsv-1) and compared to that of acv and l-polylysines (4-15 kda) using fixed or suspended vero cell lines. esterified whey proteins and their peptic hydrolyzates displayed protective action against hsv-1, which was relatively lower than that induced by acv or l-polylys ...200717990848
the prevalence of human herpesvirus 6 in human sensory ganglia and its co-occurrence with alpha-herpesviruses.human herpesvirus 6 (hhv-6) persists in the central nervous system, but its prevalence in the peripheral nervous system, a preferred latency site for herpesviruses, has not been studied. using nested polymerase chain reaction (pcr), the authors determined the distribution of hhv-6 in human sensory ganglia. hhv-6 was present in 30% of trigeminal, 40% of geniculate, 25% of vestibular, and 55% of dorsal root ganglia. it co-occurred with alpha-herpesviruses (herpes simplex virus type 1 or varicella- ...200717994431
alphaherpes viral genes and their functionsin this chapter the emphasis is on viral replication and on the viral gene products that define the outcome of the interaction of the alphaherpesviruses with their host. viral replicative and host management functions account for some of the rnas and a large number of proteins encoded by the viruses. there are, however, numerous viral gene products whose functions have not been identified or which do not play a prominent role in viral replication in the systems in which t ...200721348062
molecular basis of hsv latency and reactivationprimary infection with hsv-1 or hsv-2 results in productive replication of the virus at the site of infection, following the pattern of gene expression described elsewhere in this volume. during this initial phase, virus enters sensory neurons via their termini and retrograde transport takes the genome to the neuronal nuclei in the sensory ganglia that innervate the infected dermatome. at early times after infection, virus replication occurs in ganglionic neurons but with ...200721348106
antiviral therapy of hsv-1 and -2the discovery of effective antiviral agents has been facilitated by advances in the fields of molecular biology and virology. in the pre-antiviral era, the widely held belief was that any therapeutically meaningful interference with viral replication would destroy the host cell upon which viral replication was dependent. a growing understanding of host cell–virus interactions and viral replication, however, has led to the development of safe and effective antivirals. thes ...200721348126
persistence in the population: epidemiology, transmissionherpes simplex viruses are among the most ubiquitous of human infections. the frequency of hsv infection has been measured by testing various populations for the presence of antibody, as both virus and the immune response are thought to persist after infection for the life of the host. worldwide, ∼90% of people have one or both viruses. hsv-1 is the more prevalent virus, with 65% of persons in the united states having antibodies to hsv-1 (xu et al., 2002). the epidemiology in ...200721348128
trapped: a molecular-level look at how herpes disables its immune destroyer. 200620076586
risk factors of herpes simplex virus type 2 among std clinic attenders in delhi, india.the present study was conducted to determine the seroprevalence and risk factors associated with hsv-2 infection among sexually transmitted diseases (std) clinic attenders of delhi in india. out of 128 patients included, 76 were males and 52 were females. antibodies to hsv 1 and 2 and hiv infection were determined by elisa. syphilis seropositivity was determined by vdrl test and confirm by tpha test. ulcer scrapping were stained by giemsa for herpes progenitalis and donovan bodies and grams for ...200617913210
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
synthesis and biological evaluation of some pyrrolo[2,3-d]pyrimidines.pyrrolo[2,3-d]pyrimidine and tetrazolopyrimidine derivatives 2a, b-5a, b were prepared. also, acyclic and cyclic c-nucleosides 7a, b-12a, b were prepared by treating compound 6 with some aldoses. all prepared products were tested for antiviral activity against hepatitis-a virus (hav, mbb-cell culture adapted strain) and herpes simplex virus type-1 (hsv-1). plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with tested compounds. compound 2a sh ...200617149793
super paramagnetic clustering of dna sequences.an unsupervised clustering of 4541 dna sequences containing active promoter regions from vertebrate and arthropod classes (including their viral genes) was performed. all necessary information was solely gathered a priori from the dna sequences by measuring frequencies of tri-nucleotides and tetra-nucleotides. we employed super paramagnetic clustering, a novel clustering algorithm based on physical properties of an inhomogeneous granular ferromagnet. this method utilizes swendsen-wang cluster mo ...200619669432
a cluster of nosocomial herpes simplex virus type 1 pneumonia in a medical intensive care unit.we report a cluster of 3 cases of nosocomial herpes simplex virus type 1 (hsv-1) pneumonia occurring in close temporal and physical proximity during a 1-week period, which suggested a common source. hsv-1 nosocomial pneumonia occurs in immunocompetent intubated patients and presents as otherwise unexplained profound and/or prolonged hypoxemia (decreased f(io2), increased p(o2), and decreased a-a gradient) and "failure to wean." the diagnosis of hsv-1 pneumonia is determined by demonstration of c ...200617080387
immunological profiles of patients with chronic myeloid leukaemia. i. state before the start of treatment.in view of the increasing interest in the immunotherapy of cml it seems highly desirable to broaden the present knowledge on the immune reactivity of cml patients. a group of 24 patients and 24 healthy controls were studied for the total of 15 immunological parameters, including the prevalence of antibodies against human herpesviruses and papillomaviruses. to clearly discriminate between changes associated with the disease and those induced by the therapy, all patients were enrolled prior to the ...200617089915
latency of alpha-herpes viruses is accompanied by a chronic inflammation in human trigeminal ganglia but not in dorsal root ganglia.the immune response to latent herpesvirus infections was compared in human trigeminal ganglia (tg) and dorsal root ganglia (drg) of 15 dead individuals. on the basis of our previous findings, we hypothesized that t-cells would be attracted to sensory neurons latently infected with herpes simplex virus type 1 (hsv-1), but not to those harboring latent varicella zoster virus (vzv). we showed that the tg contain a positive hybridization signal for hsv-1 latency-associated transcript (lat), whereas ...200617021407
treatment of schwannomas with an oncolytic recombinant herpes simplex virus in murine models of neurofibromatosis type 2.gene therapy for schwannomas was evaluated in two mouse models of neurofibromatosis type 2 (nf2): (1) a transgenic model in which mice express a dominant mutant form of merlin and spontaneously develop schwannomas, and (2) a xenograft model in which human schwannoma tissue is implanted subcutaneously into immune- compromised mice. in both models, schwannoma volumes were monitored by magnetic resonance imaging (mri) and showed strong gadolinium enhancement typical of these tumors in humans. both ...200616409122
the inner tegument promotes herpes simplex virus capsid motility along microtubules in vitro.after viral fusion, capsids of the neurotropic herpes simplex virus are transported along microtubules (mt) to the nuclear pores for viral genome uncoating, nuclear transcription and replication. after assembly and egress from the nucleus, cytosolic capsids are transported to host membranes for secondary envelopment or to the axon terminal for further viral spread. using gfp-tagged capsids, cy3-labelled mt and cytosol, we have reconstituted viral capsid transport in vitro. in the presence of atp ...200616420530
dynamic expression of chemokines and the infiltration of inflammatory cells in the hsv-infected cornea and its associated tissues.the chemotactic signals regulating cell trafficking in the herpes simplex virus type 1 (hsv-1) infected cornea are well documented, however, those in the cornea-associated tissues, such as the trigeminal ganglion (tg) and draining lymph nodes (lns), are largely unknown.200617056459
receptor cross-linking on human plasmacytoid dendritic cells leads to the regulation of ifn-alpha production.plasmacytoid dendritic cells (pdc) are the natural type i ifn-producing cells that produce large amounts of ifn-alpha in response to viral stimulation. during attempts to isolate pdc from human pbmc, we observed that cross-linking a variety of cell surface receptors, including blood dc ag (bdca)-2, bdca-4, cd4, or cd123 with abs and immunobeads on pdc leads to inhibition of ifn-alpha production in response to hsv. to understand the mechanisms involved, a number of parameters were investigated. c ...200617056507
cytobiological consequences of calcium-signaling alterations induced by human viral proteins.since calcium-signaling regulates specific and fundamental cellular processes, it represents the ideal target of viral proteins, in order for the virus to control cellular functions and favour its persistence, multiplication and spread. a detailed analysis of reports focused on the impact of viral proteins on calcium-signaling has shown that virus-related elevations of cytosolic calcium levels allow increased viral protein expression (hiv-1, hsv-1/2), viral replication (hbx, enterovirus 2b, htlv ...200617059849
[intrathecal administration of hsv-i amplicon vector-mediated hppe gene therapy of nocicepion in rats with formalin pain].to investigate the antinociceptive effect of intrathecal administration of hsv-i amplicon vector-mediated hppe.200617062943
[the first genetic basis of herpetic encephalitis]. 200617063654
the stability of herpes simplex virus type i genomes in infected vero cells undergoing viral induced apoptosis.maintaining the viral genome intact following infection and prior to replication is critical to the virus life cycle. here we report an analysis of the stability of herpes simplex virus type 1 (hsv-1) genomes, relative to host chromosomal dna, in infected cells as a function of viral induced apoptosis. the results show that, in the absence of dna replication, the input genomes of wild-type (kos), and replication compromised icp27 deleted (d27-1) virus are remarkably stable. intracellular half-li ...200617065130
integerrimides a and b, cyclic heptapeptides from the latex of jatropha integerrima.two new cyclic heptapeptides, integerrimides a and b, have been isolated from the latex of jatropha integerrima. their structures were elucidated by using extensive 1d and 2d nmr, ms, and chemical degradation. at 50 microm both peptides 1 and 2 significantly inhibited neurite outgrowth in neuronal cell culture. they also partially inhibited proliferation of human ipc-298 melanoma cells as well as migration of human capan ii pancreatic carcinoma cells, but were inactive in hsv-1, antifungal, and ...200617067157
herpes simplex virus type 1 and respiratory disease in critically-ill patients: real pathogen or innocent bystander?herpes simplex virus type 1 (hsv-1) has been associated with pulmonary disease, mostly in severely immunocompromised patients. after reactivation and shedding in the oropharynx, the virus may reach the lower respiratory tract by aspiration or by contiguous spread. hsv-1 can be detected in clinical specimens by virus culture or quantitatively by nucleic acid amplification techniques. with these techniques, hsv-1 is often detected in the respiratory secretions of critically-ill patients. however, ...200617002604
common and specific properties of herpesvirus ul34/ul31 protein family members revealed by protein complementation assay.the proteins encoded by the ul34 and ul31 genes of herpes simplex virus are conserved among herpesviruses. they form a complex that is essential for the egress of the herpesvirus nucleocapsids from the nucleus. in previous work on the homologous protein complex in murine cytomegalovirus (mcmv), we defined their mutual binding domains. here, we started to map binding domains within the ul34/ul31 proteins of alpha-, beta-, and gammaherpesviruses and to locate other functional properties. a protein ...200617005637
prevalence of herpes simplex virus types 1 and 2 among children and adolescents attending a sexual abuse clinic.children and adolescents with a history of sexual abuse are at risk for acquiring herpes simplex virus (hsv) type 2. we evaluated the prevalence of hsv-1 and hsv-2 and the usefulness for this population of 2 commercially available tests.200617006285
revolt: radiation-enhanced viral oncolytic therapy.viral oncolytic therapy has been pursued with renewed interest as the molecular basis of carcinogenesis and viral replication has been elucidated. genetically engineered, attenuated viruses have been rationally constructed to achieve a therapeutic index in tumor cells compared with surrounding normal tissue. many of these attenuated mutant viruses have entered clinical trials. here we review the preclinical literature demonstrating the interaction of oncolytic viruses with ionizing radiation and ...200617011442
antiviral property and mechanisms of a sulphated polysaccharide from the brown alga sargassum patens against herpes simplex virus type 1.a sulphated polysaccharide (sp-2a) from the brown alga sargassum patens (kütz.) agardh (sargassaceae) was found to significantly inhibit the in vitro replication of both the acyclovir (acv)-sensitive and -resistant strains of herpes simplex virus type 1 (hsv-1), in dose-dependent manners, with 50% inhibitions occurring with 1.5-5.3 microg/ml of the polysaccharide. sp-2a exhibited extracellular virucidal activity only against the acv-sensitive strains, but not the resistant strain, at the concent ...200616427262
triple combination of oncolytic herpes simplex virus-1 vectors armed with interleukin-12, interleukin-18, or soluble b7-1 results in enhanced antitumor efficacy.conditionally replicating herpes simplex virus-1 (hsv-1) vectors are promising therapeutic agents for cancer. insertion of therapeutic transgenes into the viral genome should confer desired anticancer functions in addition to oncolytic activities. herein, using bacterial artificial chromosome and two recombinase-mediated recombinations, we simultaneously created four "armed" oncolytic hsv-1, designated vhsv-b7.1-ig, vhsv-interleukin (il)-12, vhsv-il-18, and vhsv-null, which express murine solubl ...200616428511
transgenic reporter mouse for bioluminescence imaging of herpes simplex virus 1 infection in living mice.bioluminescence imaging allows spatial and temporal progression of viral infection to be detected and quantified in living mice, thereby providing a new approach for studies of viral-host pathogenesis. it has been necessary to construct and validate recombinant reporter viruses that express firefly luciferase to investigate viral replication and spread with this imaging technology. this strategy greatly limits the ability to analyze multiple strains of virus and/or existing viral mutants, and re ...200616430938
characterization of a spliced exon product of herpes simplex type-1 latency-associated transcript in productively infected cells.the latency-associated transcripts (lats) of herpes simplex virus type-1 (hsv-1) are the only viral rnas accumulating during latent infections in the sensory ganglia of the peripheral nervous system. the major form of lat that accumulates in latently infected neurons is a 2 kb intron, spliced from a much less abundant 8.3 primary transcript. the spliced exon mrna has been hard to detect. however, in this study, we have examined the spliced exon rna in productively infected cells using ribonuclea ...200616938324
role for 3-o-sulfated heparan sulfate as the receptor for herpes simplex virus type 1 entry into primary human corneal fibroblasts.herpes simplex virus type 1 (hsv-1) infection of the corneal stroma remains a major cause of blindness. primary cultures of corneal fibroblasts (cf) were tested and found susceptible to hsv-1 entry, which was confirmed by deconvolution imaging of infected cells. plaque assay and real-time pcr demonstrated viral replication and hence a productive infection of cf by hsv-1. a role for glycoprotein d (gd) receptors in cultured cf was determined by gd interference assay. reverse transcription-pcr ana ...200616940509
herpes simplex virus type 1 latently infected neurons differentially express latency-associated and icp0 transcripts.during the latent phase of herpes simplex virus type 1 (hsv-1) infection, the latency-associated transcripts (lats) are the most abundant viral transcripts present in neurons, but some immediate-early viral transcripts, such as those encoding icp0, have also been reported to be transcribed in latently infected mouse trigeminal ganglia (tg). a murine oro-ocular model of herpetic infection was used to study icp0 gene expression in the major anatomical sites of hsv-1 latency, including the tg, supe ...200616940542
invader plus method detects herpes simplex virus in cerebrospinal fluid and simultaneously differentiates types 1 and 2.we report here on the development and validation of a prototype invader plus method for the qualitative detection of herpes simplex virus types 1 and 2 in cerebrospinal fluid (csf). the method combines pcr and invader techniques in a single, closed-tube, continuous-reaction format that gives an analytical sensitivity of approximately 10 copies per reaction. the clinical sensitivity and specificity were 100.0% and 98.6%, respectively, when the results of the method were validated against the resu ...200616954297
ctl response compensation for the loss of an immunodominant class i-restricted hsv-1 determinant.the t-cell response to even complex pathogens is often focused on only a handful of immunodominant determinants. such narrow responses provoke a selective pressure that can drive the emergence of ctl escape variants, raising the question of whether a broader response, targeting multiple non-dominant peptides may be more beneficial. to examine the ability of the t-cell repertoire to respond to non-dominant determinants, we have investigated how mutating the dominant peptide in hsv affects the mag ...200616956387
reactivation from quiescence does not coincide with a global induction of herpes simplex virus type 1 transactivators.herpes simplex virus type 1 (hsv-1) reactivates from a small fraction of latently infected neurons in vivo and neuronally differentiated (nd), quiescently infected (qif)-pc12 cells in vitro. this may be the result of reactivation initiating in only a few cells, or reactivation followed by premature termination of the productive virus life cycle in many or even a majority of cells. to examine the viral stress response, hsv-1 promoters of representative alpha, beta, and gamma class genes were exam ...200616972030
long-term monitoring of transplanted islets using positron emission tomography.islet transplantation can restore glucose homeostasis in those with type 1 diabetes; however, most recipients eventually lose graft function. a noninvasive method to monitor islets following transplantation would enable assessment of their survival and aid the development of therapeutics to prolong graft survival. here, we show that recombinant lentivirus can be used to engineer human islets to express a positron emission tomography (pet) reporter gene. following transplantation into mice, trans ...200616982215
improved hsv-1 amplicon packaging using virion host shutoff mutants lacking mrnase activity.given their generous transgene capacity and inherent neurotropism, herpes simplex virus (hsv-1)-based viral vectors are promising tools for gene delivery to the central nervous system. despite their widespread pre-clinical use, vector toxicity remains a concern with regard to the use of herpes vectors in humans. one potential source of toxicity stems from the tegument-associated virion host shutoff protein (vhs), which induces translational arrest in the host cell through non-specific mrnase act ...200616989006
primary treatment of acute retinal necrosis with oral antiviral therapy.to explore the possibility of oral antiviral therapy in lieu of intravenous acyclovir for treating acute retinal necrosis (arn), a necrotizing retinopathy caused by herpes simplex virus type 1 or 2 or by varicella zoster virus.200616996614
broad spectrum antimicrobial activity of leukocyte extracts from the american alligator (alligator mississippiensis).leukocytes were isolated from whole blood of wild alligators by differential sedimentation. the leukocytes were disrupted in 5% acoh and the crude extracts processed by ultrafiltration. the extracts were subjected to solvent exchange (0.1% acoh) and the fraction that contained macromolecules between 1 and 10 kda were subjected to further analyses. the acid extracts of the alligator leukocytes exhibited substantial antimycotic activities against six of eight species of candida yeast tested. in ad ...200616298430
development of the loop-mediated isothermal amplification method for rapid detection of cytomegalovirus dna.cytomegalovirus (cmv) loop-mediated isothermal amplification (lamp) was performed on dna extracted from cmv (ad-169)-, herpes simplex virus (hsv) 1 (kos)-, hsv-2 (186)-, varicella-zoster virus (oka-vaccine)-, human herpesvirus (hhv)-6 a (u1102)-, hhv-6 b (z29)-, and hhv-7 (rk)-infected cells. although amplified cmv demonstrated typical ladder patterns, no lamp product was detected in reactions performed with other viral dnas. the sensitivity of the cmv lamp was 500 copies/tube, as determined by ...200616289345
point mutations in herpes simplex virus type 1 oril, but not in oris, reduce pathogenesis during acute infection of mice and impair reactivation from latency.in vitro studies of herpes simplex virus type 1 (hsv-1) viruses containing mutations in core sequences of the viral origins of dna replication, oril and oris, that eliminate the ability of these origins to initiate viral-dna synthesis have demonstrated little or no effect on viral replication in cultured cells, leading to the conclusion that the two types of origins are functionally redundant. it remains unclear, therefore, why origins that appear to be redundant are maintained evolutionarily in ...200616352568
the herpes simplex virus type 1 vhs-ul41 gene secures viral replication by temporarily evading apoptotic cellular response to infection: vhs-ul41 activity might require interactions with elements of cellular mrna degradation machinery.we have previously shown that herpes simplex virus type 1 (hsv-1) infection is associated with early destabilization/degradation of infected cell mrnas and consequent shutoff of host protein synthesis by the activity of the virion-associated host shutoff (vhs) ul41 protein. wild-type (wt) virus destabilized/degraded the housekeeping beta-actin and alpha-tubulin mrnas as well host stress functions, like the heat shock 70 protein induced postinfection. vhs mutants did not degrade the mrnas. elabor ...200616352574
acute limbic encephalitis: a new entity?clinical cases similar to herpes simplex virus (hsv) encephalitis have accumulated in japan. detailed examinations have failed to demonstrate hsv infection. recently, these cases have been named "non-herpetic acute limbic encephalitis". only a single autopsy case was so far reported in an abstract form, because many cases showed a good prognosis. the case presented here was that following fever, a 59-year-old woman developed disturbance of consciousness and uncontrollable generalized seizures. b ...200616364542
differential susceptibility of equine and mouse brain microvascular endothelial cells to equine herpesvirus 1 infection.equine herpesvirus 1 (ehv-1) shows endotheliotropism in the central nervous system (cns) of infected horses. however, infection of endothelial cells has not been observed in the cns of infected mice. to explore the basis for this difference in endotheliotropism, we compared the susceptibility of equine brain microvascular endothelial cells (ebmecs) and mouse brain microvascular endothelial cells (mbmecs) to ehv-1 infection. the kinetics of viral growth in ebmecs was typical of a fully productive ...200616328147
synthesis and antiviral evaluation of cyclic and acyclic 2-methyl-3-hydroxy-4-pyridinone nucleoside derivatives.a series of cyclic and acyclic nucleoside analogues derived from 3-hydroxy-4-pyridinone were synthesized using the vorbrüggen reaction. iron chelation studies, and antiviral evaluation against a broad panel of viruses, were performed. the pk(a) value of ligand 25 and the stability constant of the corresponding iron(iii) complex were compared to those of deferiprone. the pfe(3+) values were found to be similar. some compounds showed moderate activity against both wild-type hsv-1 and hsv-2, as wel ...200616392791
the kaposi's sarcoma-associated herpesvirus g protein-coupled receptor as a therapeutic target for the treatment of kaposi's sarcoma.the kaposi's sarcoma-associated herpesvirus (kshv) encodes a g protein-coupled receptor (vgpcr) that has been implicated in the initiation of kaposi's sarcoma, identifying vgpcr as an attractive target for preventing kaposi's sarcoma. however, as only a fraction of cells in advanced kaposi's sarcoma lesions express vgpcr, it is unclear whether this unique viral oncogene contributes to kaposi's sarcoma progression. we therefore set out to determine whether the few cells that express vgpcr in esta ...200616397229
etiology of aseptic meningitis and encephalitis in an adult population.to investigate the etiology of aseptic meningitis and encephalitis in an adult population using modern microbiologic methods.200616401850
herpes simplex virus disrupts nf-kappab regulation by blocking its recruitment on the ikappabalpha promoter and directing the factor on viral genes.herpes simplex viruses (hsvs) are able to hijack the host-cell ikappab kinase (ikk)/nf-kappab pathway, which regulates critical cell functions from apoptosis to inflammatory responses; however, the molecular mechanisms involved and the outcome of the signaling dysregulation on the host-virus interaction are mostly unknown. here we show that in human keratinocytes hsv-1 attains a sophisticated control of the ikk/nf-kappab pathway, inducing two distinct temporally controlled waves of ikk activity ...200616407234
pilot study of oncolytic viral therapy using mutant herpes simplex virus (hf10) against recurrent metastatic breast cancer.an oncolytic herpes simplex virus type 1 mutant (hf10) has been isolated and evaluated for antitumor efficacy in a syngeneic immunocompetent mouse model, where it was effective against cancer and conferred resistance to rechallenge with tumor cells in all surviving mice. several studies have shown that hf10 is effective and safe for use against localized or peritoneally disseminated nonneuronal malignant tumors in animals.200616865590
eclipse phase of herpes simplex virus type 1 infection: efficient dynein-mediated capsid transport without the small capsid protein vp26.cytoplasmic dynein,together with its cofactor dynactin, transports incoming herpes simplex virus type 1 (hsv-1) capsids along microtubules (mt) to the mt-organizing center (mtoc). from the mtoc, capsids move further to the nuclear pore, where the viral genome is released into the nucleoplasm. the small capsid protein vp26 can interact with the dynein light chains tctex1 (dynlt1) and rp3 (dynlt3) and may recruit dynein to the capsid. therefore, we analyzed nuclear targeting of incoming hsv1-delta ...200616873277
interferon alpha in the establishment of latency by herpes simplex virus type 1 strain tr.the effect of interferon (ifn) alpha on the establishment and maintenance of neuronal latency and viral reactivation is still not known. using cell culture methods and sensitive rt-pcr methods, we show that the presence of antiserum to ifn alpha promotes the establishment of hsv-1 tr latent infection. we suggest that ifn alpha is an important tool not only for the control of productive but also latent hsv-1 infection.200616878604
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