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the essential lesion of alzheimer disease: a surprise in retrospect.in the absence of any naturally occurring animal model of alzheimer's disease (ad), the british conviction in the 1970's that clinicopathological investigations of human cases offered the best approach to unraveling the pathogenesis of ad rapidly influenced clinical neuroscientists, neuropathologists and funding agencies in canada and the usa. but as with my confreres, years of our quantifying ad lesions in autopsy brains have yet to yield definitive conclusions about what is the most important ...200616914842
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
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
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
the ul4 gene of pseudorabies virus encodes a minor infected-cell protein that is dispensable for virus replication.although homologues of the open reading frame (orf) ul4 of herpes simplex virus 1 (human herpesvirus 1) have been found in the genomes of all hitherto-analysed alphaherpesviruses, little is known about their function. in a project to analyse systematically, in an isogenic and standardized assay system, the gene products of the alphaherpesvirus pseudorabies virus (prv; suid herpesvirus 1), the prv ul4 gene product was identified using a monospecific rabbit antiserum prepared against a bacterial f ...200616894189
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
herpes simplex infection--part ii: management of hsv infections.oral and perioral herpes simplex virus infections are commonly seen and managed by the dental practitioner. many topical and oral antiviral agents are available in israel. however, only a few regimens are based on solid evidence. the purpose of this study was to review the mode of action of antiviral agents and to present therapeutic regimens supported by randomized control trials.200616886871
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
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
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
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
comparative study of macrophage response in mice after dna immunization and infection with herpes simplex virus type 1.functional activity of macrophages and intensity of t cell immune response in mice were studied after intravaginal and intraperitoneal infection with herpes simplex virus type 1 and dna vaccination in combination with adjuvant treatment (recombinant granulocyte-macrophage colony-stimulating factor and glucosaminylmuramyl dipeptide). dna vaccination induced a virus-specific t cell immune response with no macrophagic inflammatory reaction. infection with herpes simplex virus type 1 was accompanied ...200516848234
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
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
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
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
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
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
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
hsv neutralizing antibodies further refinement in preventing neonatal herpes infection. 200616813741
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 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
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
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
[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
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
hsv-1 amplicon vectors are an efficient gene transfer system for skeletal muscle cells.hsv-1 amplicon vectors have been considered as a promising gene delivery system for gene therapy of skeletal muscle diseases, due to the ability to infect non-dividing cells such as differentiated muscle cells, and to accommodate large transgenes such as the 14-kb dystrophin cdna. studies revealed that hsv-1 amplicons can transduce cultured differentiated and undifferentiated muscle cells with high efficiency. studies also revealed that hsv-1 amplicons are capable of delivering at least 23-kb tr ...200616787188
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
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
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
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
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
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
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
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
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 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
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
genital hsv-1 infections. 200616731663
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
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
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
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 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
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
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
[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
[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
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
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
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
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
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
[herpes vector-mediated gene therapy]. 200616615499
[new paradigm of herpes simplex virus type 1 thymidine kinase (hsv-tk)/ganciclovir (gcv)]. 200616615496
[development of conditionally replicating oncolytic hsv vector--targeted gene therapy for sarcoma by oncolytic viruses]. 200616615493
[meningitis]. 200616615482
[acute retinal necrosis due to herpesviridae infections]. 200616615476
[epidemiology of genital herpes]. 200616615470
[molecular mechanisms for suppression of interferon system by hsv-1 infection]. 200616615462
[hsv genes and their function]. 200616615453
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
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
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
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
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
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
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
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
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
icp0 is not required for efficient stress-induced reactivation of herpes simplex virus type 1 from cultured quiescently infected neuronal cells.viral genes sufficient and required for herpes simplex virus type 1 (hsv-1) reactivation were identified using neuronally differentiated pc12 cells (nd-pc12 cells) in which quiescent infections with wild-type and recombinant strains were established. in this model, the expression of icp0, vp16, and icp4 from adenovirus vectors was sufficient to reactivate strains 17+ and kos. the transactivators induced similar levels of reactivation with kos; however, 17+ responded more efficiently to icp0. to ...200616537603
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
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
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
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
[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
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
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
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
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
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
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
interactions between dna viruses, nd10 and the dna damage response.nd10 are small nuclear substructures that are defined by the presence the promyelocytic leukaemia protein pml. many other proteins have been detected within nd10, a complexity that is reflected in reports of their involvement in multiple cellular pathways that include the regulation of gene expression, chromatin dynamics, protein modification, apoptosis, p53 function, senescence, dna repair, the interferon response and viral infection. this review summarizes recent evidence of similarities betwe ...200616469050
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
[autophagic host defense mechanism]. 200616457203
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
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
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
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
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
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
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
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
famciclovir for the treatment of recurrent genital and labial herpes lesions.famciclovir (famvir, novartis) is an effective treatment for herpes zoster and herpes simplex. two separate studies recently examined the effectiveness of single high doses of famciclovir for treating recurrent genital herpes and labial herpes (cold sores). in the randomized, placebo-controlled studies, patients initiated treatment at the first onset of symptoms. for the treatment of genital herpes, a 1,000 mg b.i.d. dose of famciclovir had significant advantages over the placebo, reducing the t ...200516408140
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
sexually transmitted infections, blood-borne viruses and risk behaviour in an australian senior high school population--the shlirp study.to determine the feasibility and acceptability of screening for sexually transmitted infections and blood-borne viruses and to study the profile of sexual activity and other risk behaviours in a senior high school population.200516402670
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
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
evaluation of antiviral activity of compounds isolated from ranunculus sieboldii and ranunculus sceleratus.nineteen compounds isolated from ranunculus sieboldii and ranunculus sceleratus were tested for inhibitory effects on hepatitis b virus (hbv) and herpes simplex virus type-1 (hsv-1). the results showed that apigenin 4'- o- alpha-rhamnopyranoside, apigenin 7- o- beta-glucopyranosyl-4'- o- alpha-rhamnopyranoside, tricin 7- o- beta-glucopyranoside, tricin, and isoscopoletin possessed inhibitory activity against hbv replication. protocatechuyl aldehyde exhibited an inhibiting activity on hsv-1 repli ...200516395649
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
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