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localization of herpes simplex virus type 1 ul37 in the golgi complex requires ul36 but not capsid structures.the herpes simplex virus type 1 (hsv-1) ul37 gene encodes a 120-kda polypeptide which resides in the tegument structure of the virion and is important for morphogenesis. the goal of this study was to use green fluorescent protein (gfp) to follow the fate of ul37 within cells during the normal course of virus replication. gfp was inserted in frame at the c terminus of ul37 to generate a fluorescent-protein-tagged ul37 polypeptide. a virus designated k37egfp, which replicated normally on vero cell ...200818787001
asymptomatic shedding of herpes simplex virus 1 and 2: implications for prevention of transmission. 200818783317
hsv-1 infection suppresses tgf-beta1 and smad3 expression in human corneal epithelial cells.the present study was undertaken to investigate whether transforming growth factor-beta (tgf-beta) isoforms (tgf-beta1, tgf-beta2, and tgf-beta3) and smads (smad2 and smad3) are involved in herpes simplex virus type 1 (hsv-1) corneal infection.200818776948
suppression of transcription factor early growth response 1 reduces herpes simplex virus lethality in mice.herpes simplex virus type 1 (hsv-1) infection is the most common cause of sporadic, fatal encephalitis, but current understanding of how the virus interacts with cellular factors to regulate disease progression is limited. here, we show that hsv-1 infection induced the expression of the cellular transcription factor early growth response 1 (egr-1) in a human neuronal cell line. egr-1 increased viral replication by activating promoters of viral productive cycle genes through binding to its corres ...200818769632
glutamine deprivation causes enhanced plating efficiency of a herpes simplex virus type 1 icp0-null mutant.isoleucine deprivation of cellular monolayers prior to infection has been reported to result in partial complementation of a herpes simplex virus type 1 (hsv-1) icp0 null (icp0(-)) mutant. we now report that glutamine deprivation alone is able to enhance the plating efficiency of an icp0(-) virus and that isoleucine deprivation has little or no effect. because a low glutamine level is associated with stress and because stress is known to induce reactivation, low levels of glutamine may be releva ...200818768961
a novel and highly efficient production system for recombinant adeno-associated virus vector.recombinant adeno-associated virus (raav) has proven to be a promising gene delivery vector for human gene therapy. however, its application has been limited by difficulty in obtaining enough quantities of high-titer vector stocks. in this paper, a novel and highly efficient production system for raav is described. a recombinant herpes simplex virus type 1 (rhsv-1) designated hsv1-rc/deltaul2, which expressed adeno-associated virus type2 (aav-2) rep and cap proteins, was constructed previously. ...200218763068
pet imaging of heat-inducible suicide gene expression in mice bearing head and neck squamous cell carcinoma xenografts.the ability to achieve tumor selective expression of therapeutic genes is an area that needs improvement for cancer gene therapy to be successful. one approach to address this is through the use of promoters that can be controlled by external means, such as hyperthermia. in this regard, we constructed a replication-deficient adenovirus that consists of a mutated herpes simplex virus 1 thymidine kinase (mtk) fused to enhanced green fluorescent protein (egfp) under the control of the full-length h ...200918758434
viral encephalitis and epilepsy.viral encephalitis presents with seizures not only in the acute stage but also increases the risk of late unprovoked seizures and epilepsy. acute symptomatic and late unprovoked seizures in different viral encephalitides are reviewed here. among the sporadic viral encephalitides, herpes simplex encephalitis (hse) is perhaps most frequently associated with epilepsy, which may often be severe. seizures may be the presenting feature in 50% patients with hse because of involvement of the highly epil ...200818754956
herpes simplex virus ge/gi and us9 proteins promote transport of both capsids and virion glycoproteins in neuronal axons.following reactivation from latency, alphaherpesviruses replicate in sensory neurons and assemble capsids that are transported in the anterograde direction toward axon termini for spread to epithelial tissues. two models currently describe this transport. the separate model suggests that capsids are transported in axons independently from viral envelope glycoproteins. the married model holds that fully assembled enveloped virions are transported in axons. the herpes simplex virus (hsv) membrane ...200818753205
role of cdk9 in the optimization of expression of the genes regulated by icp22 of herpes simplex virus 1.icp22 is a multifunctional herpes simplex virus 1 (hsv-1) regulatory protein that regulates the accumulation of a subset of late (gamma(2)) proteins exemplified by u(l)38, u(l)41, and u(s)11. icp22 binds the cyclin-dependent kinase 9 (cdk9) but not cdk7, and this complex in conjunction with viral protein kinases phosphorylates the carboxyl terminus of rna polymerase ii (pol ii) in vitro. the primary function of cdk9 and its partners, the cyclin t variants, is in the elongation of rna transcripts ...200818753202
therapeutic efficacy of a herpes simplex virus with radiation or temozolomide for intracranial glioblastoma after convection-enhanced delivery.the herpes simplex virus-1 (hsv-1)-infected cell protein 0 (icp0) is an e3 ubiquitin ligase implicated in cell cycle arrest and dna repair inhibition. convection-enhanced delivery (ced) of either the replication-defective, icp0-producing hsv-1 mutant, d106, or the recombinant d109, devoid of all viral genome expression, was performed to determine the in vivo efficacy of icp0 in combination with ionizing radiation (ir) or systemic temozolomide (tmz) in the treatment of glioblastoma multiforme (gb ...200818728637
surfen, a small molecule antagonist of heparan sulfate.in a search for small molecule antagonists of heparan sulfate, we examined the activity of bis-2-methyl-4-amino-quinolyl-6-carbamide, also known as surfen. fluorescence-based titrations indicated that surfen bound to glycosaminoglycans, and the extent of binding increased according to charge density in the order heparin > dermatan sulfate > heparan sulfate > chondroitin sulfate. all charged groups in heparin (n-sulfates, o-sulfates, and carboxyl groups) contributed to binding, consistent with th ...200818725627
analysis of the interaction between the ul11 and ul16 tegument proteins of herpes simplex virus.the ul11 and ul16 tegument proteins of herpes simplex virus are conserved throughout the herpesvirus family. previous studies have shown that these proteins interact, perhaps to link ul16-bound nucleocapsids to ul11, which resides on the cytoplasmic face of the trans-golgi network, where maturation budding occurs. little is known about the interaction except that it requires the leucine-isoleucine (li) and acidic cluster motifs in ul11 and that no other viral proteins are involved. in particular ...200818715918
characterization of a crm1-dependent nuclear export signal in the c terminus of herpes simplex virus type 1 tegument protein ul47.the herpes simplex virus type 1 tegument protein known as vp13/14, or hul47, localizes to the nucleus and binds rna. using fluorescence loss in photobleaching analysis, we show that hul47 undergoes nucleocytoplasmic shuttling during infection. we identify the hul47 nuclear export signal (nes) as a c-terminal 10-residue hydrophobic peptide and measure its efficiency relative to that of the classical human immunodeficiency virus type 1 rev nes. finally, we show that the hul47 nes is sensitive to t ...200818715912
fulminant hepatic failure for herpes simplex virus.although exceedingly rare, fulminant hepatic failure in immunocompetent patients can develop with primary or recurrent infection due to herpes simplex virus. the diagnosis is frequently obscured by the absence of mucocutaneous involvement. elevated transaminases with leucopenia and a relatively low bilirubin level may provide clues to the diagnosis. here a female patient, 43 years, presented with the complaints of increasing jaundice, anorexia, nausea, vomiting for one week duration. she had hep ...200818705269
tracing of the molecular remnants of herpes virus infections in necrotic skin tissue.we have established an assay system to detect herpesvirus-derived transcripts in lesional crusts. fifteen patients with herpes simplex (hs), 21 with herpes zoster (hz), 2 with varicella, and 20 with irrelevant diseases were enrolled in the present study. total rna was extracted from crusts or scales, and converted to cdna. virus-encoded transcripts were amplified using reverse transcriptase (rt)-pcr. housekeeping gene transcripts such as beta2-microglobulin (beta2-mg) and beta-actin (beta-actin) ...200818693150
prophylactic effects of echinacea purpurea polysaccharide against lethal ocular herpes simplex virus type i. 200818690323
human cytomegalovirus ul18 utilizes us6 for evading the nk and t-cell responses.human cytomegalovirus (hcmv) us6 glycoprotein inhibits tap function, resulting in down-regulation of mhc class i molecules at the cell surface. cells lacking mhc class i molecules are susceptible to nk cell lysis. hcmv expresses ul18, a mhc class i homolog that functions as a surrogate to prevent host cell lysis. despite a high level of sequence and structural homology between ul18 and mhc class i molecules, surface expression of mhc class i, but not ul18, is down regulated by us6. here, we desc ...200818688275
icp34.5-dependent and -independent activities of salubrinal in herpes simplex virus-1 infected cells.the small molecule salubrinal has antiviral activity against herpes simplex virus-1 (hsv-1) and inhibits dephosphorylation of eif2 alpha mediated by the hsv-1 protein icp34.5. we investigated whether salubrinal's activities in infected cells depend on icp34.5. an icp34.5 deletion mutant was as sensitive as wild type hsv-1 to salubrinal inhibition of plaque formation in vero cells. however, salubrinal induced formation of syncytia in infected vero cells, which was enhanced by icp34.5 mutations. e ...200818684481
[the genes associated with geldanamycin inhibiting replication of herpes simplex virus type 1].geldanamycin (ga), an ansamycin antibiotic specifically binding heat shock protein 90 (hsp90), exhibits a broad-spectrum antiviral effect. herpes simplex virus type 1(hsv-1) replication in vitro was significantly inhibited by ga treatment. to explore the antiviral mechanism of ga against hsv-1, the 7267-spot human long oligonucleotide microarrays were applied to investigate the genes which might involved in the antiviral activity of ga in hela cells infected by hsv-1. meanwhile, the reverse regu ...200818683558
herpes simplex virus load in bronchoalveolar lavage fluid is related to poor outcome in critically ill patients.to evaluate the relationship between the hsv-1 and -2 loads in bal fluid (balf) and clinical outcome.200818679655
construction and production of recombinant herpes simplex virus vectors.virus vectors have been employed as gene transfer vehicles for various pre-clinical and clinical gene therapy applications. replication-competent herpes simplex virus (hsv) vectors that replicate specifically in actively dividing glial tumor cells have been used in phase i-ii human trials in patients with glioblastoma multiforme (gbm), a fatal form of brain cancer. research during the last decade on the development of hsv vectors has resulted in the engineering of recombinant vectors that are to ...200818679619
involvement of hvem receptor in activation of nuclear factor kappab by herpes simplex virus 1 glycoprotein d.the uv-inactivated herpes simplex virus 1 (hsv-1) and glycoprotein d (gd) of hsv-1 have been shown to activate nuclear factor kappab (nf-kappab) in u937 cells, but mechanisms involved in this activation have not been elucidated. here we report that: (i) uv-inactivated hsv-1 induced an increased nf-kappab activation in cells expressing human hvem (for herpesvirus entry mediator) at surface level, naturally or following stable transfection, but not in cells in which this receptor was not detected ...200818671825
ly49h is necessary for genetic resistance to murine cytomegalovirus.natural killer (nk) cells play critical roles in antiviral immunity. while the importance of effector mechanisms such as interferons has been demonstrated through knockout mice, specific mechanisms of how viruses are recognized and controlled by nk cells are less well defined. previous genetic studies have mapped the resistance genes for murine cytomegalovirus (mcmv), herpes simplex virus-1 (hsv-1), and ectromelia virus to the nk gene complex on murine chromosome 6, a region containing the polym ...200818668236
gender-dependent hla-dr-restricted epitopes identified from herpes simplex virus type 1 glycoprotein d.in recent clinical trials, a herpes simplex virus (hsv) recombinant glycoprotein d (gd) vaccine was more efficacious in woman than in men. here we report six hla-dr-restricted t-cell gd epitope peptides that bind to multiple hla-dr (dr1, dr4, dr7, dr13, dr15, and drb5) molecules that represent a large proportion of the human population. four of these peptides recalled naturally primed cd4(+) t cells in up to 45% of the 46 hsv-seropositive, asymptomatic individuals studied. for the gd(49-82), gd( ...200818667634
lymphoid-related cd11c+ cd8alpha+ dendritic cells are involved in enhancing herpes simplex virus type 1 latency.the mechanism(s) by which herpes simplex virus type 1 (hsv-1) latency is established in neurons is not known. in this study, we examined the effect of dendritic cells (dcs) on the level of hsv-1 latency in trigeminal ganglia (tgs) of ocularly infected balb/c and c57bl/6 mice. we found that immunization of wild-type mice with fms-like tyrosine kinase 3 ligand (flt3l) dna, which increases the number of dcs, increased the amount of latency in infected mice. conversely, depletion of dcs was associat ...200818667491
thymidine kinase sequence analysis of herpes simplex virus type 1 strains present in different compartments in an atypical impetiginous rash on the lesional skin of a burn patient.we report the case of a 23-year-old male burn patient with an unusual herpes simplex virus (hsv) skin manifestation. the clinical symptoms and results of hsv type 1 (hsv-1) ul23 polymorphism analysis from saliva and lesional skin underscores the need for performing molecular analysis of hsv-1 infections in burned patients presenting unusual skin lesions.200818632917
exercise stress increases susceptibility to influenza infection.exercise stress is associated with an increased risk for upper respiratory tract infection (urti) while moderate exercise has been associated with a decreased risk. we have shown that exercise stress can increase susceptibility (morbidity, symptom severity and mortality) to hsv-1 respiratory infection, but there is little evidence on the effects of stressful exercise on susceptibility to the principal etiological agents of human respiratory infections, including influenza viruses. this study exa ...200818616997
comprehensive characterization of extracellular herpes simplex virus type 1 virions.the herpes simplex virus type 1 (hsv-1) genome is contained in a capsid wrapped by a complex tegument layer and an external envelope. the poorly defined tegument plays a critical role throughout the viral life cycle, including delivery of capsids to the nucleus, viral gene expression, capsid egress, and acquisition of the viral envelope. current data suggest tegumentation is a dynamic and sequential process that starts in the nucleus and continues in the cytoplasm. over two dozen proteins are as ...200818596102
the enhanced dna replication fidelity of a mutant herpes simplex virus type 1 dna polymerase is mediated by an improved nucleotide selectivity and reduced mismatch extension ability.we previously demonstrated that a recombinant herpes simplex virus containing a mutation within the finger domain of dna polymerase replicated dna with increased fidelity. in this study, we demonstrate that, compared with wild-type polymerase, the mutant enzyme exhibited improved nucleotide selectivity and a reduced ability to extend from mismatched primer termini, which would contribute to the increased dna replication fidelity.200818596099
identification of a novel higher molecular weight isoform of usp7/hausp that interacts with the herpes simplex virus type-1 immediate early protein icp0.the herpes simplex virus type-1 (hsv-1) regulatory protein icp0, a ring-finger e3 ubiquitin ligase, stimulates the onset of viral lytic replication and the reactivation of quiescent viral genomes from latency. like many ubiquitin ligases icp0 induces its own ubiquitination, a process that can lead to its proteasome-dependent degradation. icp0 counteracts this activity by recruiting the cellular ubiquitin-specific protease usp7/hausp. here we show that icp0 can also interact with a previously uni ...200818590780
ocular hsv-1 latency, reactivation and recurrent disease.ocular infection with hsv-1 continues to be a serious clinical problem despite the availability of effective antivirals. primary infection with hsv-1 can involve ocular and adenaxial sites and can manifest as blepharitis, conjunctivitis, or corneal epithelial keratitis. after initial ocular infection, hsv-1 can establish latent infection in the trigeminal ganglia for the lifetime of the host. during latency, the viral genome is retained in the neuron without producing viral proteins. however, ab ...200818584563
comparison of nested-polymerase chain reaction and virus culture for the diagnosis of genital herpes simplex virus infection.this study was performed to compare nested-polymerase chain reaction (pcr) with viral culture as a diagnostic tool for genital herpes simplex virus (hsv) infection in a sexually transmitted infection (sti) clinic in singapore.200818581019
inhibition of herpes simplex virus types 1 and 2 in vitro infection by sulfated derivatives of escherichia coli k5 polysaccharide.herpes simplex virus type 1 (hsv-1) and hsv-2 are neurotropic viruses and common human pathogens causing major public health problems such as genital herpes, a sexually transmitted disease also correlated with increased transmission and replication of human immunodeficiency virus type 1 (hiv-1). therefore, compounds capable of blocking hiv-1, hsv-1, and hsv-2 transmission represent candidate microbicides with a potential added value over that of molecules acting selectively against either infect ...200818573926
influenza virus infection and risk of acute myocardial infarction.increasing evidences have shown that pathogens might promote atherosclerosis and trigger acute myocardial infarction (ami). but the conclusions from various studies on the correlation between previous influenza virus (iv) infection and ami were inconsistent. we conducted a case-control study to assess the association of previous iv infection and ami. questionnaire survey was conducted to collect information about demographic characteristics and heart disease risk factors. fasting blood sample wa ...200818568394
prevalence of human herpes virus types 1-7 in the semen of men attending an infertility clinic and correlation with semen parameters.to determine the prevalence of herpes viruses in the semen of an asymptomatic male cohort with and without infertility problems and its association with altered semen parameters.200918565516
detection and quantitative analysis of human herpesvirus in pilocytic astrocytoma.we investigated the hypothetical role of human herpesviruses (hhvs) in tumour formation of the cerebellum. thirty-five samples of pilocytic astrocytoma and 10 control samples of cerebellum from patients who died of unrelated diseases were examined. presence of the 8 known hhvs was first studied using specific real-time quantitative polymerase chain reaction (qpcr) targeting viral dna polymerase. hhv's dna polymerase was found present in 20 samples (7 controls, 13 astrocytomas) and was absent in ...200818565499
human breast tumor cells express multimodal imaging reporter genes.human zr75-1 cells were among the first few characterized estrogen-dependent mammary gland carcinoma cell lines and had been utilized in various studies for the pro- or antitumor effect of xenoestrogens and antiestrogens. the objective of this study was to establish a breast tumor model in zr75-1 cells bearing multimodal reporter genes to allow noninvasive imaging of tumor growth using fluorescence and nuclear imaging platforms.200818560942
the ul15 protein of herpes simplex virus type 1 is necessary for the localization of the ul28 and ul33 proteins to viral dna replication centres.the ul15, ul28 and ul33 proteins of herpes simplex virus type 1 (hsv-1) are thought to comprise a terminase complex responsible for cleavage and packaging of the viral genome into pre-assembled capsids. immunofluorescence studies confirmed that shortly after infection with wild-type hsv-1 these three proteins localize to viral dna replication compartments within the nucleus, identified by the presence of the single-stranded dna-binding protein, icp8. in cells infected with either ul28- or ul33-n ...200818559942
herpes simplex virus type 1 induces filopodia in differentiated p19 neural cells to facilitate viral spread.herpes simplex virus type-1 (hsv-1) is a neurotropic virus with significant potential as a viral vector for central nervous system (cns) gene therapy. this study provides visual evidence that recombinant green fluorescent protein (gfp)-expressing hsv-1 travel down dendrites in differentiated p19 neuronal-like cells to efficiently reach the soma. the virus also promotes cytoskeletal rearrangements which facilitate viral spread in vitro, including often dramatic increases in dendritic filopodia. v ...200818554796
the high prevalence of herpes simplex virus type 1 dna in human trigeminal ganglia is not a function of age or gender.the purpose of this study was to determine the presence and copy numbers of herpes simplex virus type 1 (hsv-1) dna in human trigeminal ganglia (tg) with respect to age, gender, and postmortem interval (pmi). human tg (n = 174, obtained from the oregon brain bank, with data on age, gender, and pmi) were analyzed for hsv-1 dna copies (hsv-1 dna polymerase gene) by using real-time pcr. we found that 89.1% (131/147) of subjects and 90.1% (155/174) of tg contained hsv-1 dna. the copy numbers of hsv- ...200818550674
[the role of cyclin-dependent protein kinase 2 in the replication of herpes simplex virus].cyclin-dependent protein kinase (cdk) plays an important role in the replication of herpes simplex virus (hsv) and other important human disease viruses. but which kinds of cdk are required in the replication of hsv is still not clear. in this study, we infected dominant negative cdk2 cell line with different multiplicity of infection (moi) of hsv-1-kos strain (abbreviated as hsv below), and the results showed that the yield of hsv depended on the moi; the replication of hsv delayed about 3 h as ...200818533340
the many roles of the regulatory protein icp27 during herpes simplex virus infection.herpes simplex virus type 1 (hsv-1) protein icp27 is a multifunctional regulator of gene expression that assumes different roles during the course of infection. early in infection, icp27 mediates the inhibition of cellular splicing, whereas, later it helps to recruit cellular rna polymerase ii (rnap ii) to viral replication sites and to facilitate viral rna export. icp27 has also been shown to stimulate translation of viral transcripts. icp27 performs its activities by interacting with rna and w ...200818508584
ccl3 protects mice from corneal pathology during recurrent hsv-1 infection.ccl2 and ccl3 are proinflammatory chemokines that are produced during the early stages of inflammation and are known to stimulate the migration of mononuclear cells to the site of inflammation,. previous studies addressing the role of these chemokines during primary herpetic stromal keratitis (hsk), have suggested that ccl2 is involved in reducing corneal disease and that ccl3 is involved in promoting this disease. we addressed the role that these chemokines play in a recurrent model of hsk. res ...200818508519
role for a-type lamins in herpesviral dna targeting and heterochromatin modulation.posttranslational modification of histones is known to regulate chromatin structure and transcriptional activity, and the nuclear lamina is thought to serve as a site for heterochromatin maintenance and transcriptional silencing. in this report, we show that the nuclear lamina can also play a role in the downregulation of heterochromatin and in gene activation. herpes simplex virus dna initiates replication in replication compartments near the inner edge of the nucleus, and histones are excluded ...200818497856
subconjunctival antisense oligonucleotides targeting tnf-alpha influence immunopathology and viral replication in murine hsv-1 retinitis.to investigate the role of tumor necrosis factor-alpha (tnf-alpha) in immunopathology and viral replication in the contralateral eye in the von szily model of herpes simplex virus (hsv)-1 acute retinitis.200818491128
anti-inflammatory effects of fty720 against viral-induced immunopathology: role of drug-induced conversion of t cells to become foxp3+ regulators.fty720 has been used to control inflammatory lesions, but the mechanisms by which the drug acts in vivo are poorly understood. such mechanisms may result primarily from effects on lymphocyte and dendritic cell homing to lymphoid and inflammatory sites. we demonstrate that fty720 may also act by causing the conversion of tcr-stimulated nonregulatory cd4(+) t cells to foxp3(+)cd4(+) regulatory t cells and by enhancing their suppressive activity. in a model in which mice were ocularly infected with ...200818490766
glycoprotein-dependent and tlr2-independent innate immune recognition of herpes simplex virus-1 by dendritic cells.innate immune recognition is an important early event in the host response to herpes simplex virus-1 (hsv-1) infection. dendritic cells (dc) play an important sentinel role in this recognition. previous studies have shown that monocyte-derived dc (mddc) respond to hsv-1 by up-regulation of costimulatory molecules and type i ifn release, but the molecular targets on the virus recognized by the dc have not been defined. in this study we show that mddc recognize and respond to the four essential vi ...200818490753
neutrophils protect the retina of the injected eye from infection after anterior chamber inoculation of hsv-1 in balb/c mice.to determine whether infiltrating polymorphonuclear leukocytes pmns play a role in preventing early direct anterior-to-posterior spread of herpes simplex virus (hsv)-1 and/or in preventing the spread of hsv-1 from the brain back to the retina of the injected eye after anterior chamber (ac) inoculation.200818487377
[infantile perianal herpes simplex virus infection]. 200818456479
inhibition of hsv cell-to-cell spread by lactoferrin and lactoferricin.the milk protein lactoferrin (lf) has multiple functions, including immune stimulation and antiviral activity towards herpes simplex virus 1 and 2 (hsv-1 and hsv-2); antiviral activity has also been reported for the n-terminal pepsin-derived fragment lactoferricin (lfcin). the anti-hsv mode of action of lf and lfcin is assumed to involve, in part, their interaction with the cell surface glycosaminoglycan heparan sulfate, thereby blocking of viral entry. in this study we investigated the ability ...200818456345
host strain-dependent difference in susceptibility in a rat model of herpes simplex type 1 encephalitis.herpes simplex encephalitis (hse) is characterized by severe focal brain inflammation leading to substantial loss of nervous tissue. the authors established a model of herpes simplex virus type 1 (hsv)-1-induced acute encephalitis in the rat by injecting into the whiskers' area a virus strain isolated from a fatal human hse case. the model might resemble natural propagation of hsv-1 in humans; spreading from the mouth and lips via the trigeminal nerve to trigeminal ganglia and subsequently enter ...200818444082
overview of gene delivery into cells using hsv-1-based vectors.this overview describes the considerations involved in the preparation and use of herpes simplex virus type 1 (hsv-1) as a vector for gene transfer into neurons. strategies for gene delivery into neurons, either to study the molecular biology of brain function or for gene therapy, must utilize vectors that persist stably in postmitotic cells and that can be targeted both spatially and temporally in the nervous system in vivo. this unit describes the biology of hsv-1 along with a discussion cover ...200118428476
il-10 and natural regulatory t cells: two independent anti-inflammatory mechanisms in herpes simplex virus-induced ocular immunopathology.two prominent anti-inflammatory mechanisms involved in controlling hsv-1-induced corneal immunopathology (stromal keratitis or sk) are the production of the cytokine il-10 and the activity of natural regulatory t cells (ntregs). it is not known whether, under in vivo conditions, il-10 and ntregs influence the corneal pathology independently or in concert. in the current study using wild-type and il-10(-/-) animals, we have assessed the activity of ntregs in the absence of il-10 both under in vit ...200818424753
from infectious diseases to primary immunodeficiencies.the field of primary immunodeficiencies has expanded, thanks to the exploration of novel clinical phenotypes and their connection with morbid genotypes, and the subsequent exploration of new patients who have known primary immunodeficiency-defining clinical phenotypes and their connection with novel morbid genotypes. this two-way process is becoming increasingly active, particularly for patients who have infectious diseases in whom the underlying immunologic and genetic causes remain mostly unex ...200818424331
a new acycloguanosine-specific supermutant of herpes simplex virus type 1 thymidine kinase suitable for pet imaging and suicide gene therapy for potential use in patients treated with pyrimidine-based cytotoxic drugs.the herpes simplex virus type 1 thymidine kinase (hsv1-tk) gene is widely used as a suicide gene in combination with ganciclovir (gcv) and as a nuclear imaging reporter gene with an appropriate reporter probe. wild-type hsv1-tk recognizes a variety of pyrimidine and acycloguanosine nucleoside analogs, including clinically used antiviral drugs. pet of hsv1-tk reporter gene expression will be compromised in patients receiving nucleoside-based antiviral treatment. with the use of an acycloguanosine ...200818413388
use of multiplex pcr and real-time pcr to detect human herpes virus genome in ocular fluids of patients with uveitis.to measure the genomic dna of human herpes viruses (hhv) in the ocular fluids and to analyse the clinical relevance of hhv in uveitis.200818408082
partial functional complementation of a pseudorabies virus ul25 deletion mutant by herpes simplex virus type 1 pul25 indicates overlapping functions of alphaherpesvirus pul25 proteins.homologs of the ul25 gene product of herpes simplex virus 1 (hsv-1) are highly conserved among the herpesviridae. however, their exact function during viral replication is unknown. current evidence suggests that in the alphaherpesvirus pseudorabies virus (prv) the capsid-associated pul25 plays a role in primary envelopment of dna-containing mature capsids at the inner nuclear membrane. in the absence of pul25, capsids were found in close association with the inner nuclear membrane, but nuclear e ...200818400859
herpes simplex type 1 versus herpes simplex type 2 in anogenital herpes; a 10 year study from the waikato region of new zealand.to determine the proportion of herpes simplex type 1 vs herpes simplex type 2, as a cause of anogenital herpes in the waikato region. we specifically looked for changes in the proportions over time, and for gender or age group associations.200818392061
activated inflammatory infiltrate in hsv-1-infected corneas without herpes stromal keratitis.to investigate herpes stromal keratitis (hsk) immunopathology by studying hsv-1-infected corneas that fail to develop hsk.200818385067
a fusogenic segment of glycoprotein h from herpes simplex virus enhances transfection efficiency of cationic liposomes.low cellular uptake and endosomal escape are regarded as major limitations for nonviral gene delivery. in the present study, we use cationic liposomes incorporating fusogenic peptides from glycoprotein h of herpes simplex virus to improve cellular internalization and endosomal release of cationic liposome-dna complexes.200818383507
an intranasal heat shock protein based vaccination strategy confers protection against mucosal challenge with herpes simplex virus.herpes simplex virus-1 (hsv-1) represents a significant obstacle for vaccine designers, despite decades of investigation. the virus primarily infects the host at vulnerable mucosal surfaces that progresses to lesion development, latency in nervous tissue, and possible reactivation. therefore, protection at the site of infection is crucial. mucosal adjuvants are critical for the development of an effective vaccine approach and heat-shock protein 70 (hsp70) represents an attractive candidate for t ...200818382144
[pharmacological treatment of bell's palsy: favourable effects of prednisolone-based therapy now demonstrated].bell's palsy accounts for two-thirds ofall acute facial palsies. presumed reactivation of the herpes simplex virus and concurrent swelling of the facial nerve prompted the use of antivirals in combination with corticosteroids, although evidence supporting the effectiveness of this approach was weak. a recently published randomized placebo-controlled clinical trial assessed the effectiveness of adding valacyclovir to prednisolone; another larger primary-care-based study compared treatment with pr ...200818380381
escherichia coli nissle 1917 facilitates tumor detection by positron emission tomography and optical imaging.bacteria-based tumor-targeted therapy is a modality of growing interest in anticancer strategies. imaging bacteria specifically targeting and replicating within tumors using radiotracer techniques and optical imaging can provide confirmation of successful colonization of malignant tissue.200818369089
a-5021: a new acyclovir analogue inhibits murine herpetic keratitis.to determine the efficacy of a-5021, a new analogue of acyclovir, on murine herpetic keratitis.200818362663
pilralpha is a herpes simplex virus-1 entry coreceptor that associates with glycoprotein b.glycoprotein b (gb) is one of the essential components for infection by herpes simplex virus-1 (hsv-1). although several cellular receptors that associate with glycoprotein d (gd), such as herpes virus entry mediator (hvem) and nectin-1, have been identified, specific molecules that mediate hsv-1 infection by associating with gb have not been elucidated. here, we found that paired immunoglobulin-like type 2 receptor (pilr) alpha associates with gb, and cells transduced with pilralpha become susc ...200818358807
[zao "ekolab" enzyme immunoassay systems for the diagnosis of herpes simplex].the laboratory diagnosis of herpes has recently ranked among the most topical problems of modern public health care since the role of the above infection, as other torch-group infections, is constantly increasing in the development of maternal and infant diseases. for the laboratory diagnosis of herpes, zao "ekolab" has proposed the enzyme immunoassay systems "eia-hsv-1-igg", "eia-hsv-2-igg", and "eia-hsv-1,2-igm" that allow for making type-specific diagnosis of herpes and for determining the ch ...200818354919
entry of herpesviruses into mammalian cells.the mechanism that herpesviruses use to enter cells is one of the most complex viral entry mechanisms studied so far. this complexity seems to mount as new participants, both cellular receptors and viral glycoproteins, are identified. recent structural work on entry glycoproteins gd and gb from herpes simplex virus (hsv) 1 has illuminated the functional roles of these glycoproteins in the process of entry. in doing so, it provided information on the mechanism of two critical steps of hsv entry: ...200818351291
[the n1-18 terminus of marek's disease virus vp22 is essential for protein transduction].we previously showed some differences in marek's disease virus (mdv) vp22 gene between virulent and avirulent strains, in the deletion from 201aa to 206aa, namely 201tksert206. in this study, vp22 genes were amplified from strains: cvi988/rispens and ga. and then the fragments were subcloned into pcdna3.1/zeo(+), respectively, which were co-expressed with an enhancer green fluorescent protein (egfp) after transfection into cos-1 cells. as with both human herpesvirus 1 and bovine herpesvirus 1 vp ...200818338583
live visualization of herpes simplex virus type 1 compartment dynamics.we have constructed a recombinant herpes simplex virus type 1 (hsv-1) that simultaneously encodes selected structural proteins from all three virion compartments-capsid, tegument, and envelope-fused with autofluorescent proteins. this triple-fluorescent recombinant, rhsv-ryc, was replication competent, albeit with delayed kinetics, incorporated the fusion proteins into all three virion compartments, and was comparable to wild-type hsv-1 at the ultrastructural level. the vp26 capsid fusion protei ...200818337577
genotypic detection of acyclovir-resistant hsv-1: characterization of 67 acv-sensitive and 14 acv-resistant viruses.infections due to herpes simplex virus (hsv) resistant to acyclovir (acv) represent an important clinical concern in immunocompromised patients. in order to switch promptly to an appropriate treatment, rapid viral susceptibility assays are required. we developed herein a genotyping analysis focusing on thymidine kinase gene (tk) mutations in order to detect acyclovir-resistant hsv in clinical specimens. a total of 85 hsv-1 positive specimens collected from 69 patients were analyzed. tk gene coul ...200818336925
the in vitro anti-herpes simplex virus type-1 and type-2 activity of long dan xie gan tan, a prescription of traditional chinese medicine.long dan xie gan tan (ldxgt), a decoction of radix gentianae for purging the pathogenic inflammation of the liver, is a widely used prescription among many in traditional chinese medicine. the prescription is primarily used to treat the disorders induced by damp-heat in the liver and the gall bladder.200818332627
alzheimer's disease-like changes in herpes simplex virus type 1 infected cells: the case for antiviral therapy. 200818328007
evaluation of real-time polymerase chain reaction assays for the detection of herpes simplex virus in swab specimens.an in-house herpes simplex virus (hsv) real-time polymerase chain reaction (pcr) hydrolysis probe assay and three commercial real-time hsv assays were evaluated for the detection of hsv from genital, oral, ocular and dermal clinical samples. five hundred and sixty samples from patients displaying signs and symptoms of hsv infection were used to evaluate the in-house hsv assay. a representative 151 samples were processed using the artus hsv-1/2 tm pcr kit, smartcycler non-typing and smartcycler t ...200818322714
uniocular anterior chamber inoculation of a tumor necrosis factor alpha-expressing recombinant of herpes simplex virus type 1 results in more rapid destruction and increased viral replication in the retina of the uninoculated eye.tumor necrosis factor alpha (tnf-alpha) has been shown to have a protective role in the eyes and brains of herpes simplex virus type 1 (hsv-1)-infected mice. to determine whether overexpression of tnf-alpha affected the course of virus infection following uniocular anterior chamber inoculation, a recombinant of hsv-1 that produces tnf-alpha constitutively (kostnf) was constructed. balb/c mice were injected with the tnf-alpha recombinant, a recombinant containing the pci plasmid, a recombinant re ...200818321975
phenoxazine derivatives inactivate human cytomegalovirus, herpes simplex virus-1, and herpes simplex virus-2 in vitro.we examined whether phenoxazine derivatives, 2-amino-4,4alpha-dihydro-4alpha-7-dimethyl-3h-phenoxazine-3-one (phx-1), 3-amino-1,4alpha-dihydro-4alpha-8-dimethyl-2h-phenoxazine-2-one (phx-2), and 2-amino-phenoxazine-3-one (phx-3) may have antiviral activity against herpes family viruses: human cytomegalovirus (hcmv), herpes simplex virus type 1 (hsv-1), and herpes simplex virus type 2 (hsv-2). the antiviral activity was evaluated by the selectivity index (si), which is the ratio of 50% cytotoxic ...200818319567
antiviral activities of coffee extracts in vitro.both hot water extracts of coffee grinds and instant coffee solutions inhibited the multiplication of herpes simplex virus type 1, a representative enveloped dna virus, when they were added to the culture medium of the virus-infected cells at a dose of one fifth the concentration suitable for drinking. the antiherpetic activity was independent of the suppliers (companies) of the coffee grinds and of the locations where the coffee beans were produced. further characterization revealed that there ...200818314244
herpes simplex labialis in children with acute falciparum malaria. 200818313630
the identification and characterization of fusogenic domains in herpes virus glycoprotein b molecules.the molecular mechanism of entry of herpes viruses requires a multicomponent fusion system. virus entry and cell-cell fusion of herpes simplex virus (hsv) requires four glycoproteins: gd, gb and gh/gl. the role of gb remained elusive until recently, when the crystal structure of hsv-1 gb became available. glycoprotein b homologues represent the most highly conserved group of herpes virus glycoproteins; however, despite the high degree of sequence and structural conservation, differences in post- ...200818311743
prevalence of human papillomavirus and herpes simplex virus type 2 infection in korean commercial sex workers.in order to investigate the prevalence of sexually transmitted viruses such as human papillomavirus (hpv) and herpes simplex virus (hsv) in korean commercial sex workers (csws), we selected 188 csws (age range 20-44 years, median age 24 years) who regularly visited one public health center in seoul, korea. hpv genotypes were analyzed by using a hpv dna chip, and an enzyme-linked immunosorbent assay (elisa) was used to detect type-specific igg against hsv2 antibody identifying seropositivity for ...200818309283
identification of two small rnas within the first 1.5-kb of the herpes simplex virus type 1-encoded latency-associated transcript.the herpes simplex virus type 1 (hsv-1) latency-associated transcript (lat) is abundantly expressed in latently infected neurons. in the rabbit or mouse ocular models of infection, expression of the first 1.5 kb of lat coding sequences is sufficient for and necessary for wild-type levels of spontaneous reactivation from latency. the antiapoptosis functions of lat, which maps to the same 1.5 kb of lat, are important for the latency-reactivation cycle because replacement of lat with other antiapop ...200818300074
apoptosis regulators fas and bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity.apoptotic death of t lymphocytes is critical for shutdown of immune responses and hemopoietic cell homeostasis. both death receptor (fas) activation and mitochondrial apoptosis triggered by the bh3-only protein bim have been implicated in the killing of antigen-stimulated t cells. we examined mice lacking the gene encoding bim (bcl2l11) and with the inactivating lpr mutation in the gene encoding fas (fas), designated bcl2l11(-/-)fas(lpr/lpr) mice. shutdown of an acute t cell response to herpes s ...200818275830
sequences in the ul11 tegument protein of herpes simplex virus that control association with detergent-resistant membranes.the product of the ul11 gene of hsv-1 is a small, membrane-bound tegument protein with features that are conserved among all herpesviruses. for all viruses examined, mutants lacking this protein (or its homolog) have budding defects and accumulate capsids in the cytoplasm of the infected cell. ul11 binds to the cytoplasmic faces of host membranes via n-terminal myristate and nearby palmitate moieties. these fatty-acid modifications are typical of proteins that localize to detergent-resistant mem ...200818261757
human cytomegalovirus-specific cd4+ and cd8+ t-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection.human cytomegalovirus infection is the most frequent viral complication in patients undergoing hematopoietic stem cell transplantation. we investigated the development of human cytomegalovirus-specific t cells in adult recipients of hematopoietic stem cell transplants.200818245650
an hsv-1 gd mutant virus as an entry-impaired live virus vaccine.hsv-1 glycoprotein d (gd) interacts with hvem and nectin-1 cell receptors to initiate virus entry. we prepared an hsv-1 strain with mutations in the gd gene at amino acid residues 3 and 38 by changing alanine to cysteine and tyrosine to cysteine, respectively (a3c/y38c). these mutations were constructed with the intent of evaluating infection in vivo when virus enters by hvem but not nectin-1 receptors and were based on prior reports demonstrating that purified gda3c/y38c protein binds to hvem b ...200818243431
detection of herpes virus dna in post-operative thyroid tissue specimens of patients with autoimmune thyroid disease.to demonstrate any differences in the detection of herpes simplex virus type 1 and 2, cytomegalovirus, human herpes virus type 6 and 7 dna from thyroid tissue blocks of patients with autoimmune thyroid disease and multi-nodular goiter and to propose few mechanisms, which could explain the possible role of herpesvirus infection in the development of thyroid autoimmune responses.200818240111
attenuated multimutated herpes simplex virus-1 effectively treats prostate carcinomas with neural invasion while preserving nerve function.many cancers can cause disability and pain by invading nerves. in particular, prostate carcinoma has a high propensity for neural invasion (ni) at an early stage. attempted surgical treatment of tumors with ni often leads to erectile dysfunction and deteriorated quality of life. therefore, there is a need for novel modalities that will selectively target cancer cells while preserving neural function. herpes simplex viruses (hsvs) have a natural trophism for peripheral nerves. we hypothesized tha ...200818234972
synthesis of 99mtc(co)3-deoxyuridine derivatives as potential hsv1-tk gene expression imaging agents.in this study, we synthesized (99m)tc(co)(3)-2'-aminomethylpyridyl-2'-deoxyuridine ((99m)tc(co)(3)-ampdu) and (99m)tc(co)(3)-aminoethylpyridyl-2'-deoxyuridine ((99m)tc(co)(3)-aepdu) as potential agents for imaging the expression of the non-invasive herpes simplex virus type-1 thymidine kinase. ampdu and aepdu were synthesized from uridine in five chemical steps and then labeled with [(99m)tc(co)(3)(h(2)o)(3)](+) (370mbq/0.5 ml) at 100 degrees c for 10 min. under optimal conditions (0.5 and 1.0mg ...200818222693
knockin mice expressing a chimeric p53 protein reveal mechanistic differences in how p53 triggers apoptosis and senescence.the contribution of transcriptional activation to the p53 effector functions critical for tumor suppression, apoptosis and cellular senescence, remains unclear because of p53's ability to regulate diverse cellular processes in a transactivation-independent manner. dissociating the importance of transactivation from other p53 functions, including regulating transcriptional repression, dna replication, homologous recombination, centrosome duplication, and mitochondrial function, has been difficult ...200818216268
successful treatment of neonatal herpes simplex-type 1 infection complicated by hemophagocytic lymphohistiocytosis and acute liver failure.neonatal disseminated herpes simplex virus (hsv) infection with acute liver failure (alf) and neonatal hemophagocytic lymphohistiocytosis (hlh) are severe diseases. we recently experienced a male infant with hlh and alf induced by hsv type 1 (hsv-1). the infant, born at 39 weeks of gestation by normal delivery, developed a fever on day 4. on day 9, laboratory investigations showed progressive liver dysfunction and coagulopathy, and the serum ferritin was excessively elevated. furthermore, the bl ...200818212481
murine gammaherpesvirus 68 serum antibodies in general human population.previous studies using elisa and virus neutralization test (vnt) have proved the presence of murine gammaherpesvirus 68 (mhv-68) serum antibodies in sera of laboratory staff working with mhv-68, as well as in the general population. in this study, we investigated the incidence of serum antibodies to mhv-68 and to human herpesviruses presumably antigenically similar to mhv-68, as herpes simplex virus 1 (hsv-1), human cytomegalovirus (hcmv), and epstein-barr virus (ebv), in general population usin ...200718197737
evaluation of the t-rex transcription switch for conditional expression and regulation of hsv-1 vectors.herpes simplex virus 1 (hsv-1) strain ang and angpath were cloned as bacterial artificial chromosome (bac). two different types of bac genomes were obtained. bac genomes of type i contained the bac replicon at the intended target region between the genes of ul48 and ul49. in bac genomes of type ii, the bac sequences were found to be aberrantly fused between the termini of the hsv-1 genome. both the bac types were used to establish a conditional gene expression system for hsv-1 by flp recombinase ...200818193347
in vivo evaluation of the uptake of [(123)i]fiau, [(123)i]ivfru and [(123)i]ivfau by normal mouse brain: potential for noninvasive assessment of hsv-1 thymidine kinase gene expression in gliomas.radioiodinated 5-iodo-1-(2-fluoro-2-deoxy-beta-d-arabinofuranosyl)uracil (f *iau) is most commonly used for noninvasive assessment of herpes simplex virus type 1 thymidine kinase (hsv-1-tk) gene expression. however, it does not permeate the intact blood-brain barrier (bbb) because of its moderate lipophilicity. in this work, three iodo-nucleosides, fiau, ivfru, and ivfau, were radiolabeled with iodine-123 and tested for permeation of the bbb in mice and for potential measurement of hsv-1-tk gene ...200818188770
dissecting the structural determinants of the interaction between the human cytomegalovirus ul18 protein and the cd85j immune receptor.ul18 is a glycoprotein encoded by the human cytomegalovirus genome and is thought to play a pivotal role during human cytomegalovirus infection, although its exact function is still a matter of debate. ul18 shares structural similarity with mhc class i and binds the receptor cd85j on immune cells. besides ul18, cd85j binds mhc class i molecules. the binding properties of cd85j to mhc class i molecules have been thoroughly studied. conversely, very little information is available on the cd85j/ul1 ...200818178836
characterization of mre11 loss following hsv-1 infection.herpes simplex virus induces the activation of the cellular dna double strand break response pathway dependent upon initiation of viral dna replication. the mrn complex, consisting of mre11, rad50 and nbs1, is an essential component of the dna double strand break response and other reports have documented its presence at sites of viral dna replication, interaction with icp8 and its contribution to efficient viral dna replication. during our characterization of the dsb response following infectio ...200818177684
c-reactive protein mediates the effect of apolipoprotein e on cytomegalovirus infection.although the apolipoprotein (apoe)-epsilon4 allele has been shown to determine the outcome of several infections, its relationship with cytomegalovirus (cmv) has not been explored. we examine whether apoe determines cmv and herpes simplex virus type 1 (hsv-1) antibody levels and assess whether c-reactive protein (crp) mediates any observed relationships.200818171282
nuclear egress and envelopment of herpes simplex virus capsids analyzed with dual-color fluorescence hsv1(17+).to analyze the assembly of herpes simplex virus type 1 (hsv1) by triple-label fluorescence microscopy, we generated a bacterial artificial chromosome (bac) and inserted eukaryotic cre recombinase, as well as beta-galactosidase expression cassettes. when the bac phsv1(17(+))bluelox was transfected back into eukaryotic cells, the cre recombinase excised the bac sequences, which had been flanked with loxp sites, from the viral genome, leading to hsv1(17(+))bluelox. we then tagged the capsid protein ...200818160444
binding of icp4, tata-binding protein, and rna polymerase ii to herpes simplex virus type 1 immediate-early, early, and late promoters in virus-infected cells.the binding of herpes simplex virus type 1 icp4, tata-binding protein (tbp), and rna polymerase ii (polii) to the promoter regions of representative immediate-early (ie) (icp0), early (e) (thymidine kinase [tk]), and late (l) (glycoprotein c [gc]) genes on the viral genome was examined as a function of time postinfection, viral dna replication, cis-acting sites for tfiid in the tk and gc promoters, and genetic background of icp4. the binding of tbp and polii to the ie icp0 promoter was independe ...200818094162
the essential human cytomegalovirus gene ul52 is required for cleavage-packaging of the viral genome.replication of human cytomegalovirus (hcmv) produces large dna concatemers of head-to-tail-linked viral genomes that upon packaging into capsids are cut into unit-length genomes. the mechanisms underlying cleavage-packaging and the subsequent steps prior to nuclear egress of dna-filled capsids are incompletely understood. the hitherto uncharacterized product of the essential hcmv ul52 gene was proposed to participate in these processes. to investigate the function of pul52, we constructed a delt ...200818077717
terpenoids and phenolics from plectranthus strigosus, bioactivity screening.further studies on plectranthus sp. (lamiaceae) led to the isolation of terpenes and phenol esters from plectranthus strigosus benth. ent-16-kauren-19-ol (1), ent-16-kauren-19-oic acid (2), xylopic acid (3), xylopinic acid (4), hinokiol (5), 4 beta,6 beta-dihydroxy-1 alpha,5 beta(h)-guai-9-ene (6) 4 beta,6 beta-dihydroxy-1 alpha,5 beta(h)-guai-10(14)-ene (7), mixtures of hexacosan-1,26-diol and octacosan-1,28-diol ferulate diesters (8), of esters from ferulic acid and fatty alcohols (9) and of e ...200818075900
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