Publications

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rna-binding of the human cytomegalovirus transactivator protein ul69, mediated by arginine-rich motifs, is not required for nuclear export of unspliced rna.the human cytomegalovirus protein pul69 belongs to a family of regulatory factors that is conserved within the herpesviridae and includes the proteins icp27 of herpes simplex virus type 1 and eb2 of epstein-barr virus. icp27 and eb2 have been shown to facilitate the nuclear export of viral mrnas via interacting with the cellular mrna export factor ref. furthermore, direct rna-binding of these proteins was found to be essential for their stimulating effects on mrna export. recently, we demonstrat ...200616500893
epitope mapping of herpes simplex virus type 2 gh/gl defines distinct antigenic sites, including some associated with biological function.the gh/gl complex plays an essential role in virus entry and cell-cell spread of herpes simplex virus (hsv). very few immunologic reagents were previously available to either identify important functional regions or gain information about structural features of this complex. therefore, we generated and characterized a panel of 31 monoclonal antibodies (mabs) against hsv type 2 (hsv-2) gh/gl. fourteen mabs bound to a conformation-dependent epitope of the gh2/gl2 complex, and all blocked virus spr ...200616501070
[herpes simplex virus type 1 and 2 (hsv-1,2) dna detection by pcr during genital herpes].the oligonucleotide primers for herpes simplex virus type 1 and 2 dna detection are developed. in examined group of patients with genital herpes the virus of type 2 and type 1 was detected in 63% and 26% cases, respectively. the mixed infection of both types is revealed in 11% of the patients.200616512611
anatomical mapping of human herpesvirus reservoirs of infection.following primary infection, all eight human herpesviruses persist lifelong in the human host. however, a mapping of all anatomic sites of human herpesvirus persistence is lacking. fresh tissue specimens representing approximately 40 major anatomic sites from eight autopsies were screened using a recently developed real-time pcr method for detection of all eight human herpesviruses. patients with evidence of active herpesvirus infection (herpes simplex 1 (hsv-1), herpes simplex 2 (hsv-2), varice ...200616528368
neonatal herpes simplex virus infection presenting as acute liver failure: prevalent role of herpes simplex virus type i.acute liver failure (alf) in neonates is rare but carries a high mortality without liver transplantation. herpes simplex virus (hsv) is one of the microbes that more commonly causes alf and is potentially treatable; hence, early diagnosis and treatment are important to avoid progression to liver failure.200616540797
incidence and prevalence of herpes simplex virus infections in adolescent women.we conducted this study to examine the incidence, prevalence, and risk factors for herpes simplex virus (hsv) 1 and hsv 2 infection in a cohort of young women who were closely followed for acquisition of sexually transmitted infections.200616540882
type specific seroprevalence of hsv-1 and hsv-2 in four geographical regions of poland.to examine the type specific seroprevalence of herpes simplex virus (hsv) types 1 and 2 infections, stratified by age and gender, and associated risk factors for hsv-2 seropositivity in poland.200616581747
prevalence of infection with herpes simplex virus types 1 and 2 in australia: a nationwide population based survey.studies demonstrating previous herpes simplex virus (hsv) type 2 infection as a risk factor for hiv transmission, and the development of a hsv vaccine candidate, have emphasised the need for worldwide population based studies of hsv seroprevalence. the only nationwide seroprevalence studies have been conducted in the united states.200616581748
degradation of fibrillar collagen in a human melanoma xenograft improves the efficacy of an oncolytic herpes simplex virus vector.oncolytic viral therapy provides a promising approach to treat certain human malignancies. these vectors improve on replication-deficient vectors by increasing the viral load within tumors through preferential viral replication within tumor cells. however, the inability to efficiently propagate throughout the entire tumor and infect cells distant from the injection site has limited the capacity of oncolytic viruses to achieve consistent therapeutic responses. here we show that the spread of the ...200616510565
induction of cytokine expression by herpes simplex virus in human monocyte-derived macrophages and dendritic cells is dependent on virus replication and is counteracted by icp27 targeting nf-kappab and irf-3.macrophages and dendritic cells (dcs) play essential roles in host defence against microbial infections. in the present study, it is shown that human monocyte-derived macrophages and dcs express both type i and type iii interferons (ifns) [ifn-alpha, ifn-beta and interleukin 28 (il-28), il-29, respectively], tumour necrosis factor alpha and the chemokines ccl5 and cxcl10 after herpes simplex virus 1 (hsv-1) infection. the cytokine-inducing activity of hsv-1 was dependent on viability of the viru ...200616603509
mesenchymal stem cells are susceptible to human herpesviruses, but viral dna cannot be detected in the healthy seropositive individual.allogeneic stem cell transplantation is often complicated by reactivation of herpesviruses. mesenchymal stem cells (msc) are immunomodulatory and may be used to treat graft-versus-host disease. we investigated if herpesviruses infect and can be transmitted by msc, and if msc suppress immune responses to various infectious agents. mesenchymal stem cells from healthy seropositive donors were evaluated with polymerase chain reaction for the most common herpesviruses: cytomegalovirus (cmv), herpes s ...200616604097
[hsv genes and their function]. 200616615453
[molecular mechanisms for suppression of interferon system by hsv-1 infection]. 200616615462
[epidemiology of genital herpes]. 200616615470
[acute retinal necrosis due to herpesviridae infections]. 200616615476
[meningitis]. 200616615482
[development of conditionally replicating oncolytic hsv vector--targeted gene therapy for sarcoma by oncolytic viruses]. 200616615493
[new paradigm of herpes simplex virus type 1 thymidine kinase (hsv-tk)/ganciclovir (gcv)]. 200616615496
[herpes vector-mediated gene therapy]. 200616615499
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
evaluation of the cepheid herpes simplex virus typing real-time pcr assay using dermal and genital specimens.the cepheid herpes simplex virus (hsv) (cepheid, sunnyvale, ca) typing multiplex real-time polymerase chain reaction (pcr) assay was evaluated for its ability to detect hsv in dermal and genital specimens stored in m5 media. swab specimens (n = 114) for hsv testing were placed in m5 media and split between our laboratory and a highly experienced reference laboratory. aliquots for testing with the cepheid assay were processed using a simple boil-and-go procedure and then run in a smartcycler ii ( ...200616698214
a herpes simplex virus recombinant that exhibits a single-chain antibody to her2/neu enters cells through the mammary tumor receptor, independently of the gd receptors.the human epidermal growth factor receptor 2/neuregulin (her2/neu) receptor is overexpressed in highly malignant mammary and ovarian tumors and correlates with a poor prognosis. it is a target for therapy; humanized monoclonal antibodies to her2 have led to increased survival of patients with her2/neu-positive breast cancer. as a first step in the design of an oncolytic herpes simplex virus able to selectively infect her2/neu-positive cells, we constructed two recombinants, r-lm11 and r-lm11l, t ...200616699034
evaluation of herpes simplex detection in corneal scrapings by three molecular methods.herpes simplex virus (hsv)-1 keratitis (hsk) is a sight-threatening ocular infection with worldwide occurrence. a prompt laboratory diagnosis is often very useful. the purpose of this study was to evaluate molecular methods as rapid diagnostic tools compared with cell culture of hsk. corneal scrapings from patients with clinically suspected hsk were tested by direct immunofluorescence assay (ifa) for hsv-1 antigen and by polymerase chain reaction (pcr) for hsv-1 dna, and an attempt for viral iso ...200616586022
oas and pkr are not required for the antiviral effect of ad:ifn-gamma against acute hsv-1 in primary trigeminal ganglia cultures.three interferon-gamma (ifn-gamma)-induced antiviral pathways have been reported. involved antiviral proteins include: mx, rnase l/2',5'-oas, and protein kinase r (pkr). involvement of oas and pkr in ifn-gamma-induced anti-herpes simplex virus-1 (hsv-1) pathways has not been reported previously, but ifn-gamma induces oas and pkr when other viruses invade the nervous system. the aim of the current study was to determine if the absence of intact oas and pkr antiviral pathways affects the antiviral ...200616704298
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
genital hsv-1 infections. 200616731663
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
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
synthesis and antiviral evaluation of novel open-chain analogues of neplanocin a.novel acyclic nucleoside analogues were designed and synthesized as open-chain analogues of neplanocin a. the coupling of the allylic bromide with purine bases using cesium carbonate afforded a series of novel acyclic nucleosides. the synthesized compounds ia-ii were evaluated for their antiviral activity against various viruses such as hiv hsv-1, hsv-2, and ecmv.200616629127
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
serial in vivo imaging of the lung metastases model and gene therapy using hsv1-tk and ganciclovir.noninvasive imaging in lung metastatic tumor models is used infrequently because of technical limitations in detecting metastases. we have previously used 2'-fluoro-2'-deoxy-5-iodo-1-beta-d-arabinofuranosyluracil labeled with (131)i ((131)i-fiau) and demonstrated the applicability of noninvasive imaging for monitoring cancer gene therapy in an experimental animal model of herpes simplex virus type 1 thymidine kinase (hsv1-tk)-expressing tumor xenografts. we have now used the same animal model to ...200616644759
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
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
glioma virotherapy: effects of innate immune suppression and increased viral replication capacity.oncolytic viruses are genetically altered replication-competent viruses that infect, and reproduce in, cancer cells but do not harm normal cells. on lysis of the infected cells, the newly formed viruses burst out and infect other tumor cells. experiments with injecting mutant herpes simplex virus 1 (hrr3) into glioma implanted in brains of rats show lack of efficacy in eradicating the cancer. this failure is attributed to interference by the immune system. initial pretreatment with immunosuppres ...200616489036
synthesis and biological evaluation of carboacyclic nucleosides with (z) and (e)-9-[4,4-bis(hydroxymethyl)]-2-butenyl side chain.a series of carboacyclic nucleosides with (z) and (e)-9-[4,4-bis(hydroxy-methyl)]-2-butenyl side chains were synthesized as ring open analogs of cyclohexene nucleosides 1 and bioisosteres of ganciclovir 3. the (e)-isomers were obtained to compare the side chain geometry effect on antiviral activity.200616759867
2-substituted furans from the roots of polyalthia evecta.four new 2-substituted furans, 19-(2-furyl)nonadeca-5,7-diynoic acid (1), 19-(2-furyl)nonadeca-5-ynoic acid (2), 1-(2-furyl)pentacosa-7,9-diyne (3), and ester 21-(2-furyl)heneicosa-14,16-diyne-19-(2-furyl)nonadeca-5,7-diynoate (4) have been isolated from the roots of polyalthia evecta. their structures were established by spectroscopic techniques. compounds 1 and 1a showed antiplasmodial activity. the acids 1 and 2 exhibited antiviral activity against herpes simplex type 1. in addition, 5 also s ...200616441071
advances in oncolytic viral therapy.viral oncolytic therapy is under intense investigation as a novel anticancer strategy. both alone and in combination with other conventional treatment modalities, viral oncolytics exploit the natural cytotoxicity of viruses to directly kill tumor cells. results from preclinical studies demonstrating the intricate interaction between oncolytic viruses, the targeted tumors and their hosts, has resulted in new strategies being developed to overcome the challenges of maximizing oncolytic viral effic ...200616784026
prenatal diagnosis of an exceptional intrauterine herpes simplex type 1 infection.to assess ultrasound findings of a fetus with intrauterine growth retardation (iugr) and skin damage, related to intrauterine herpes simplex virus (hsv) infection.200616463294
yatein from chamaecyparis obtusa suppresses herpes simplex virus type 1 replication in hela cells by interruption the immediate-early gene expression.inhibitory effects of methanolic extracts from nine chinese herbs on herpes simplex virus type 1 (hsv-1) replication were studied. by a bioassay-guided fractionation procedure, yatein (c(22)h(23)o(7); m.w.399) was isolated from chamaecyparis obtusa; yatein significantly suppressed hsv-1 multiplication in hela cells without apparent cytotoxicity. to further localize the point in the hsv-1 replication cycle where arrest occurred, a set of key regulatory events leading to the viral multiplication w ...200616540181
structural characterization of the ul25 dna-packaging protein from herpes simplex virus type 1.herpesviruses replicate their double stranded dna genomes as high-molecular-weight concatemers which are subsequently cleaved into unit-length genomes by a complex mechanism that is tightly coupled to dna insertion into a preformed capsid structure, the procapsid. the herpes simplex virus type 1 ul25 protein is incorporated into the capsid during dna packaging, and previous studies of a null mutant have demonstrated that its function is essential at the late stages of the head-filling process, e ...200616474137
human herpesvirus 1 ul24 gene encodes a potential pd-(d/e)xk endonuclease.using meta-basic, a highly sensitive method for detection of distant similarity between proteins, we have identified another potential pd-(d/e)xk endonuclease in human herpesvirus 1 (hhv-1) encoded by the ul24 gene. the universal presence of ul24 in completed herpesviral genomes of three major subfamilies, alphaherpesvirinae, betaherpesvirinae, and gammaherpesvirinae, suggests a fundamental role for this predicted pd-(d/e)xk endonuclease activity in the viral life cycle.200616474163
cationic liposomes as potential carriers for ocular administration of peptides with anti-herpetic activity.in the present study the preparation, characterization and activity of cationic liposomes containing the secretory form of herpes simplex virus type 1 (hsv-1) glycoprotein b (gb1s) or two related polylysine rich peptides, namely dtk1 and dtk2, were described. the immunotherapeutic potential of these hsv antigens containing liposomes was examined with a rabbit ocular model of hsv-1 infection. our study indicates that the liposomes (i) are able to encapsulate quantitatively gb1s and around 30% the ...200616600535
characterization of the varicella zoster virus (vzv)-specific intra-ocular t-cell response in patients with vzv-induced uveitis.varicella zoster virus (vzv) is a well-known cause of infectious uveitis. the aim of this study was to characterize the vzv-specific t-cell response in eyes of patients with vzv-induced uveitis. t-cell lines (tcl) were generated by mitogenic stimulation of intra-ocular fluid (iof) samples obtained from eight patients with vzv-induced uveitis. two patients with herpes simplex virus (hsv)-induced uveitis were included as disease controls. characterization of individual t-cells in the tcl was perfo ...200616530754
synergistic antiviral activity of acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus.acyclovir and vidarabine both exhibit anti-herpetic activity. because different mechanisms of action of vidarabine and acyclovir have been reported, we analyzed their combined anti-herpetic activity on plaque formation of herpes simplex virus (hsv)-1, hsv-2, and varicella-zoster virus (vzv) by isobolograms. the results indicate that acyclovir and vidarabine have a synergistic effect on wild type hsv-1, hsv-2, and vzv. the susceptibility of thymidine kinase-deficient hsv-1 to vidarabine was not a ...200616797734
varicella-zoster virus open reading frame 10 is a virulence determinant in skin cells but not in t cells in vivo.the open reading frame 10 (orf10) of varicella-zoster virus (vzv) encodes a tegument protein that enhances transactivation of vzv genes and has homology to herpes simplex virus type 1 (hsv-1) vp16. while vp16 is essential for hsv replication, orf10 is dispensable for vaccine oka (voka) growth in vitro. we used parent oka (poka) cosmids to delete orf10, producing poka delta10; point mutations that disrupted the acidic activation domain and the putative motif for binding human cellular factor 1 (h ...200616537591
caspase 3 activation during herpes simplex virus 1 infection.during herpes simplex virus 1 (hsv-1) infection, apoptosis is initiated by immediate early gene transcription and is later modulated by proteins synthesized in infected cells. we have previously shown that procaspase 3 levels are reduced during hsv-1 replication. we now demonstrate that a replication-defective hsv-1 recombinant virus which is incapable of packaging viral dna into capsids activated caspase 3 but retained the ability to prevent the apoptotic process from killing the infected cells ...200616621101
site-specific proteolysis of the transcriptional coactivator hcf-1 can regulate its interaction with protein cofactors.limited proteolytic processing is an important transcriptional regulatory mechanism. in various contexts, proteolysis controls the cytoplasmic-to-nuclear transport of important transcription factors or removes domains to produce factors with altered activities. the transcriptional coactivator host cell factor-1 (hcf-1) is proteolytically processed within a unique domain consisting of 20-aa reiterations. site-specific cleavage within one or more repeats generates a family of amino- and carboxyl-t ...200616624878
hsv neutralizing antibodies further refinement in preventing neonatal herpes infection. 200616813741
the long-term but not the short-term antiviral effect of ifn-alpha depends on flt3 ligand and pdc.the cooperation between ifn-alpha/beta and fl, the ligand of fms-like tyrosine kinase 3 (flt3), plays an important role in the defense against herpes simplex virus type 1 (hsv-1) in neonates. treatment of neonatal mice with recombinant ifn-alpha has a short-term, fl-independent and a long-term, fl-dependent protective effect against hsv-1. in mice lacking fl, neonatal resistance against hsv-1 is very low and dc numbers in the spleen are reduced. the treatment of these mice with rifn-alpha at day ...200616639711
protective immunity to genital herpes simplex virus type 1 and type 2 provided by self-adjuvanting lipopeptides that drive dendritic cell maturation and elicit a polarized th1 immune response.genital herpes simplex virus type 1 and type 2 (hsv-1 and hsv-2) infections are a significant health problem worldwide. while it is believed that cd4+ th1 cells are among the effectors to herpes immunity, developing an epitope-based clinical vaccine capable of inducing an effective anti-herpes cd4+ th1-mediated protection is still under investigation. few molecules achieve this target without the aid of external immuno-adjuvant. the present study was undertaken to examine the immunogenicity in m ...200616817765
characterization of the ifn-gamma t-cell responses to immediate early antigens in humans with genital herpes.the ifn-gamma elispot assay has been used to examine the t-cell repertoire for many disease states in humans but, as yet, not genital herpes. using overlapping synthetic peptide libraries, an ifn-gamma elispot assay was established that could measure cd4 and cd8 t-cell responses to hsv-2 antigens in patients with genital herpes.200616822314
high prevalence of multiple human herpesviruses in saliva from human immunodeficiency virus-infected persons in the era of highly active antiretroviral therapy.human immunodeficiency virus (hiv) infection is associated with an increased risk for human herpesviruses (hhvs) and their related diseases. methods for limiting the transmission of hhvs require a better understanding of the prevalence and infectiousness of oral hhvs in hiv-infected patients. we performed quantitative pcr to investigate the prevalence, quantity, risk, and correlates of salivary hhvs from 58 hiv-seropositive individuals in a case control study. hhvs were significantly more preval ...200616825357
[experimental study of the facial nerve paralysis induced by herpes simplex virus type 1 infection in mice].to establish an animal model of bell palsy induced by type i herpes simplex virus (hsv-1) infection and to assess the role and site of hsv-1 in the pathogenesis of facial paralysis.200616646235
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
[animal model of facial neuritis induced by herpes simplex virus].to study the role of herpes simplex virus type 1 ( hsv-1 ) in facial paralysis by developing an experimental animal model of viral facial paralysis.200616646236
construction and characterization of bacterial artificial chromosomes containing hsv-1 strains 17 and kos.bacterial artificial chromosomes (bacs) were constructed containing full-length, infectious dna of hsv-1 strains 17 and kos. to generate bacs without altering viral genes, sequences required for selection and propagation of the bac were placed between the u(l)37 and u(l)38 genes, and flanked by loxp sites. the system was tested by studying multiple properties of these hsv-1 bac constructs in vitro and in vivo following propagation in bacteria, virus reconstitution from hsv-bac dna in eukaryotic ...200616647145
4-1bb costimulation enhances hsv-1-specific cd8+ t cell responses by the induction of cd11c+cd8+ t cells.since 4-1bb plays a predominant role in cd8+ t cell responses, we investigated the effects of 4-1bb triggering on the primary and memory cd8+ t responses to hsv-1 infection. 4-1bb was detected on 10-15% of cd4+ and cd8+ t cells following the infection. 4-1bb-positive t cells were in the proliferative mode and showed the enhanced expression of anti-apoptotic proteins. agonistic anti-4-1bb treatment exerted preferential expansion of cd8+ t cells and gb/h-2kb-positive cd8+ t cells, and enhanced cyt ...200616524567
anti-apoptotic function of a microrna encoded by the hsv-1 latency-associated transcript.micrornas (mirnas) are a class of small rna molecules that regulate the stability or the translational efficiency of target messenger rnas (mrnas). the latency-associated transcript (lat) of herpes simplex virus-1 (hsv-1) is the only viral gene expressed during latent infection in neurons. lat inhibits apoptosis and maintains latency by promoting the survival of infected neurons. no protein product has been attributed to the lat gene and the mechanism by which lat protects cells from apoptosis i ...200616738545
non-invasive bioluminescence imaging for monitoring herpes simplex virus type 1 hematogenous infection.traditional studies on viral neuroinvasiveness and pathogenesis have generally relied on murine models that require the sacrifice of infected animals to determine viral distributions and titers. the present paper reports the use of in vivo bioluminescence imaging to monitor the replication and tropism of kos strain hsv-1 viruses expressing the firefly luciferase reporter protein in hematogenously infected mice. following intraperitoneal injection, a comparison was made between real-time pcr dete ...200616682243
seroprevalence of herpes simplex virus types 1 and 2, epstein-barr virus, and cytomegalovirus in children with acute lymphoblastic leukemia in egypt.viral infection, especially caused by herpes viruses, is now recognized as an important cause of morbidity and mortality in immunocompromised cancer patients. this study aimed at studying seroprevalence of 3 herpes viruses herpes simplex virus types 1 and 2 (hsv 1 and 2), epstein-barr virus (ebv), and cytomegalovirus (cmv) in children with acute lymphoblastic leukemia (all).200616883441
a strategy for selective, cd4+ t cell-independent activation of virus-specific memory b cells for limiting dilution analysis.complete characterization of the b cell response to infection or vaccination is dependent on accurate quantitation of the memory b cell (mbc) pool. an established method for measuring mbc frequencies is limiting dilution analysis based on in vitro stimulation of mbcs to divide and differentiate into antibody-secreting cells (ascs). the presence of specific antibody then serves to identify cultures positive for precursor mbcs. the sensitivity of this approach is critically dependent on optimal in ...200616730022
role of metapneumovirus in viral respiratory infections in young children.the contribution of human metapneumovirus (hmpv) relative to that of other respiratory viruses as a cause of respiratory infections in children less than 1 year old has been evaluated. from october 2003 to april 2004, nasopharyngeal samples from 211 children less than 1 year old were analyzed to detect respiratory viruses. respiratory syncytial virus (rsv) was the predominant virus isolated (96 children [45.5%]), followed by influenza a virus, parainfluenza virus, adenovirus, cytomegalovirus, an ...200616891486
[protective effects of trichosanthin in herpes simplex virus-1 encephalitis in mice].trichosanthin (tcs), a ribosome-inactivating protein extracted from the root tuber of chinese medicinal herb trichosanthes kirilowii maximowicz, has various pharmacological properties including abortifacient, anti-tumor and anti-virus. this study aimed to evaluate the effects of tcs on infectious brain injury induced by herpes simplex virus-1 (hsv-1) in mice.200616787600
toll-like receptors, innate immunity and hsv pathogenesis.in the last decade, substantial progress has been made in understanding the molecular mechanisms involved in initial host responses to viral infections, and how viral recognition leads to the innate responses that ultimately shape the adaptive immune response. viruses, including herpes simplex virus (hsv) types 1 and 2, trigger toll-like receptors (tlrs) that elicit cytokine and chemokine production. in turn, this can create local resistance and modulate t- and b-cell-mediated immunity. tlr acti ...200616895653
transmission of herpes simplex virus types 1 and 2 in a prospective cohort of hiv-negative gay men: the health in men study.despite increasing reports of herpes simplex virus (hsv) type 1 (hsv-1)-associated anogenital herpes, there are very limited data comparing the seroepidemiological profile of and risk factors for hsv-1 and hsv type 2 (hsv-2) infection.200616897652
effects of topical anaesthetics and fluorescein on the real-time pcr used for the diagnosis of herpesviruses and acanthamoeba keratitis.the early microbiological diagnosis of corneal infections may prevent the condition from worsening.200616899529
herpes simplex virus regulatory proteins vp16 and icp0 counteract an innate intranuclear barrier to viral gene expression.hsv regulatory proteins vp16 and icp0 play key roles in launching the lytic program of viral gene expression in most cell types. however, these activation functions are dispensable in u2os osteosarcoma cells, suggesting that this cell line either expresses an endogenous activator of hsv gene expression or lacks inhibitory mechanisms that are inactivated by vp16 and icp0 in other cells. to distinguish between these possibilities, we examined the phenotypes of somatic cell hybrids formed between u ...200616750236
packaging determinants in the ul11 tegument protein of herpes simplex virus type 1.the ul11 gene of herpes simplex virus type 1 encodes a 96-amino-acid tegument protein that is myristylated, palmitylated, and phosphorylated and is found on the cytoplasmic faces of nuclear, golgi apparatus-derived, and plasma membranes of infected cells. although this protein is thought to play a role in virus budding, its specific function is unknown. purified virions were found to contain approximately 700 copies of the ul11 protein per particle, making it an abundant component of the tegumen ...200616928743
cancer-specific targeting of an adenovirus-delivered herpes simplex virus thymidine kinase suicide gene using translational control.two technical hurdles, gene delivery and target specificity, have hindered the development of effective cancer gene therapies. in order to circumvent the problem of tumor specificity, the suicide gene, hsv-1 thymidine kinase (hsv-tk), was modified with a complex 5' upstream-untranslated region (5'-utr) that limits efficient translation to cells expressing high levels of the translation initiation factor, eif4e. since previous studies have shown that most tumor cells express elevated levels of ei ...200616802401
wanderings of a dna enzymologist: from dna polymerase to viral latency.i am a member of what has been called, perhaps too grandiosely, "the greatest generation." i grew up during the great depression and served in the u.s. army during world war ii. because of my military service and the benefits of the gi bill, i was able to attend college and, later, graduate school. early in my graduate studies, i became fascinated with enzymes and the biochemical reactions that they catalyze. this fascination has never left me during the 50 years i have been a "dna enzymologist. ...200616756482
icp0 antagonizes stat 1-dependent repression of herpes simplex virus: implications for the regulation of viral latency.the herpes simplex virus type 1 (hsv-1) icp0 protein is an e3 ubiquitin ligase, which is encoded within the hsv-1 latency-associated locus. when icp0 is not synthesized, the hsv-1 genome is acutely susceptible to cellular repression. reciprocally, when icp0 is synthesized, viral replication is efficiently initiated from virions or latent hsv-1 genomes. the current study was initiated to determine if icp0's putative role as a viral interferon (ifn) antagonist may be relevant to the process by whi ...200616764725
herpes simplex virus capsid structure: dna packaging protein ul25 is located on the external surface of the capsid near the vertices.ul25 is one of seven herpes simplex virus-encoded proteins involved specifically in dna encapsidation. its role appears to be to stabilize the capsid so that dna is prevented from escaping once it has entered. to clarify the function of ul25, we have examined capsids with the goal of defining where it is located. analysis of trypsin-treated capsids showed that ul25 is sensitive to cleavage like other proteins such as the major capsid and portal proteins that are exposed on the capsid surface. in ...200616775316
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
icp0 and the us3 protein kinase of herpes simplex virus 1 independently block histone deacetylation to enable gene expression.sk-n-sh cells exposed to low ratios of icp0-null (deltaicp0) mutants of herpes simplex virus per cell express the viral alpha proteins, but the progression to beta and gamma gene expression does not ensue. in these restrictive cells, post-alpha gene expression can be induced after exposure of the infected cells to sodium butyrate, an indication that vp16 brought into cells by the virus and the alpha gene products made after infection cannot block the silencing of viral post-alpha genes by histon ...200616785443
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
chimeric herpes simplex virus/adeno-associated virus amplicon vectors.chimeric or hybrid herpes simplex virus type 1/adeno-associated virus amplicon vectors combine the large transgene capacity of hsv-1 with the potential for site-specific genomic integration and stable transgene expression of aav. these chimeric vectors have been demonstrated to support transgene expression for significantly longer periods than standard hsv-1 amplicons. moreover, hsv/aav hybrid vectors can mediate integration at the aavs1 pre-integration site on human chromosome 19 at a relativel ...200616787183
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
icp0 gene expression is a herpes simplex virus type 1 apoptotic trigger.apoptosis is a highly regulated programmed cell death process which is activated during normal development and by various stimuli, such as viral infection, which disturb cellular metabolism and physiology. that herpes simplex virus type 1 (hsv-1) induces apoptosis but then prevents its killing of infected cells is well-established. however, little is known about the viral factor/event which triggers the apoptotic process. we previously reported that infections with either (i) a temperature-sensi ...200616809287
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
amplicon vectors as outstanding tools to study and modify cognitive functions.this review summarizes recent data on the use of hsv-1-based amplicon vectors for in vivo gene delivery to the brains of rats and mice to study and modify behaviour. here we describe studies that have focused on cognitive functions like learning and memory. in addition, the use of amplicons in other behavioural studies, like addiction, social interaction, anxiety and stress, will be briefly updated. several remarkable findings have been achieved, thanks to the use of these very efficient and non ...200616787186
resistance of mrna translation to acute endoplasmic reticulum stress-inducing agents in herpes simplex virus type 1-infected cells requires multiple virus-encoded functions.via careful control of multiple kinases that inactivate the critical translation initiation factor eif2 by phosphorylation of its alpha subunit, the cellular translation machinery can rapidly respond to a spectrum of environmental stresses, including viral infection. indeed, virus replication produces a battery of stresses, such as endoplasmic reticulum (er) stress resulting from misfolded proteins accumulating within the lumen of this organelle, which could potentially result in eif2alpha phosp ...200616840316
oral and perioral herpes simplex virus type 1 (hsv-1) infection: review of its management.herpes simplex virus type 1 (hsv-1) gives rise to a variety of clinical disorders and is a major cause of morbidity and mortality worldwide. hsv-1 infections are common in oral and perioral area. the aim of the present report was to critically examine the published literature to evaluate the advantages and limitations of therapy of hsv-1 infection in both immunocompetent and immunocompromised patients. systemic antiviral therapy has been widely accepted as effective for primary herpetic gingivos ...200616700734
amplicons as vaccine vectors.hsv-1 amplicon vectors efficiently transduce cultured antigen-presenting cells (apc), including both human and murine dendritic cells as well as primary human chronic lymphocytic leukemia (cll) b cells. helper-free amplicons have been shown to be especially well-suited for this purpose, since they do not impair the antigen-presenting functions of these target cells. in vivo, amplicon vectors have been used in preclinical studies aimed at the development of therapeutic cancer vaccines, as well as ...200616787189
endonuclease g: a role for the enzyme in recombination and cellular proliferation.our earlier studies had suggested that endonuclease g (endog), a member of the evolutionarily conserved dna/rna nonspecific betabetaalpha-me-finger nuclease family, functioned in the a sequence-mediated segment inversion observed during herpes simplex virus 1 replication. to test this hypothesis, we used rna interference to reduce the level of endog in mammalian cells in culture. reduction of endog produced a small but statistically significant decrease in a sequence-mediated recombination, sugg ...200616754849
herpes simplex keratitis.herpes simplex keratitis (hsk) results from an infection with the herpes simplex virus type 1 (hsv-1) also known as human herpesvirus type 1 (hhv-1). primary infection may involve an ocular or non-ocular site, following which latency might be established principally in the trigeminal ganglion but also in the cornea. during latency, the virus appears as a circular episome associated with histones with active transcription only from the region encoding the latency-associated transcript (lat). the ...200616807055
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
human red blood cell polymorphisms and malaria.genetic factors are a major determinant of child survival in malaria endemic countries. identifying which genes are involved and how they affect the malaria disease risk potentially offers a powerful mechanism through which to learn more about the host-parasite relationship. the past few years have seen significant progress towards achieving this goal for some of the best-known malaria resistance genes that determine the structure or function of red blood cells: gerbich blood group antigen negat ...200616815736
structure of complex viruses and virus-infected cells by electron cryo tomography.in microbiology, and in particular in virus research, electron microscopy (em) is an important tool, offering a broad approach for investigating viral structure throughout their intracellular and extracellular life cycles. currently, molecular tools and rapid developments in advanced light microscopy dominate the field and supply an enormous amount of information concerning virus biology. in recent years, numerous fascinating high-resolution em structures obtained by single-particle electron cry ...200616829161
crystal structure of glycoprotein b from herpes simplex virus 1.glycoprotein b (gb) is the most conserved component of the complex cell-entry machinery of herpes viruses. a crystal structure of the gb ectodomain from herpes simplex virus type 1 reveals a multidomain trimer with unexpected homology to glycoprotein g from vesicular stomatitis virus (vsv g). an alpha-helical coiled-coil core relates gb to class i viral membrane fusion glycoproteins; two extended beta hairpins with hydrophobic tips, homologous to fusion peptides in vsv g, relate gb to class ii f ...200616840698
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
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
trapped: a molecular-level look at how herpes disables its immune destroyer. 200620076586
synthesis and antiviral activity of some 2-substituted 3-formyl- and 3-cyano-5,6-dichloroindole nucleosides.a series of dichlorinated indole nucleosides has been synthesized and tested for activity against human cytomegalovirus (hcmv) and herpes simplex virus type-1 (hsv-1) and for cytotoxicity. the isopropylidene-protected analogs of the previously reported 3-formyl-2,5,6-trichloro-1-(beta-dribofuranosyl)indole (ftcri) and 3-cyano-2,5, 6-trichloro-1-(beta-d-ribofuranosyl)indole (ctcri) were modified by nucleophilic displacement of the 2-chloro substituent using secondary amines. deprotection of the i ...200516438038
herpes simplex virus type 1 in peptic ulcer disease: an inverse association with helicobacter pylori.to assess the frequency of herpes simplex virus type i in upper gastrointestinal tract ulcers and normal mucosa with the modern and better assays and also with a larger number of well characterized patients and controls and its relationship to helicobacter pylori(h pylori).200516425358
dipeptide monoester ganciclovir prodrugs for treating hsv-1-induced corneal epithelial and stromal keratitis: in vitro and in vivo evaluations.the aim of this study was to evaluate a series of dipeptide monoester ganciclovir (gcv) prodrugs with the goal of improving ocular bioavailability of gcv from topical ophthalmic solutions.200516386088
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