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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
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
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
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
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
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
[infantile perianal herpes simplex virus infection]. 200818456479
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
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
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
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
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
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
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
[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 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
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 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
prophylactic effects of echinacea purpurea polysaccharide against lethal ocular herpes simplex virus type i. 200818690323
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
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
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
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
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
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
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
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
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
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
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
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
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
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
asymptomatic shedding of herpes simplex virus 1 and 2: implications for prevention of transmission. 200818783317
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
[construction of herpes simplex virus-1 virion protein 22-mediated microdystrophin gene recombinant adenovirus and study on the property of protein transduction].to construct the recombinant adenovirus containing herpes simplex virus-1 virion protein (vp) 22 and human microdystrophin gene, then the adenovirus was transfected into c2c12 myoblast and studied on the property of protein transduction with vp22-mediated microdystrophin in c2c12 myoblast.200818795628
anti-hsv-1 and anti-hiv-1 activity of gallic acid and pentyl gallate.the synthetic n-alkyl esters of gallic acid (ga), also known as gallates, especially propyl, octyl and dodecyl gallates, are widely employed as antioxidants by food and pharmaceutical industries. the inhibitory effects of ga and 15 gallates on herpes simplex virus type 1 (hsv-1) and human immunodeficiency virus (hiv-1) replication were investigated here. after a preliminary screening of these compounds, ga and pentyl gallate (pg) seemed to be the most active compounds against hsv-1 replication a ...200818797755
synthesis and in vitro evaluation of 5-[(18)f]fluoroalkyl pyrimidine nucleosides for molecular imaging of herpes simplex virus type 1 thymidine kinase reporter gene expression.two novel series of 5-fluoroalkyl-2'-deoxyuridines (fprdu, fbudu, fpedu) and 2'-fluoro-2'-deoxy-5-fluoroalkylarabinouridines (ffprau, ffbuau, ffpeau) that have three, four, or five methylene units (propyl, butyl, or pentyl) at c-5 were prepared and tested as reporter probes for imaging herpes simplex virus type 1 thymidine kinase (hsv1- tk) gene expression. the negishi coupling methodology was employed in efficiently synthesizing the radiolabeling precursors. all six 5-[(18)f]fluoroalkyl pyrimid ...200818800764
role for nectin-1 in herpes simplex virus 1 entry and spread in human retinal pigment epithelial cells.herpes simplex virus 1 (hsv-1) demonstrates a unique ability to infect a variety of host cell types. retinal pigment epithelial (rpe) cells form the outermost layer of the retina and provide a potential target for viral invasion and permanent vision impairment. here we examine the initial cellular and molecular mechanisms that facilitate hsv-1 invasion of human rpe cells. high-resolution confocal microscopy demonstrated initial interaction of green fluorescent protein (gfp)-tagged virions with f ...200818803666
[investigation of herpes simplex virus in viral meningoencephalitis suspected cases using molecular and serological methods].herpes simplex virus (hsv) meningoencephalitis has a high mortality rate if proper antiviral therapy is not applied. thus rapid diagnosis is of peculiar importance in such cases. in this study we aimed to evaluate the use of polymerase chain reaction (pcr) and detection of intrathecally synthesized antibodies by serological methods in viral meningoencephalitis suspected cases to determine hsv as the causative agent. seventeen cases with cerebrospinal fluid (csf) samples with microscopical and bi ...200818822885
[investigation of viral nucleic acids in middle-ear effusion specimens from children with acute otitis media].acute otitis media with effusion (ome) is one of the major causes of antibiotic use, indication for operation and hearing loss in children. in two third of the cases the etiologic agents are bacteria. nonetheless, increasing numbers of reports have implicated viruses as etiologic agents that may have some effect on prognosis of ome. the aim of this study was to investigate the presence of nucleic acids of respiratory syncytial virus (rsv) type a and b, influenza type a virus, adenovirus, cytomeg ...200818822887
herpes simplex-like infection in a bottlenose dolphin stranded in the canary islands.a bottlenose dolphin, stranded in the canary islands in 2001 exhibited non-suppurative encephalitis. no molecular detection of cetacean morbillivirus (cemv) was found, but a herpesviral-specific band of 250 bp was detected in the lung and brain. the sequenced herpesviral pcr product was compared with genbank sequences, obtaining 98% homology (p-distance of 0.02) with human herpesvirus 1 (herpes simplex virus 1 or hsv-1). this is the first report of a herpes simplex-like infection in a stranded d ...200818828564
structure-activity relationships for dipeptide prodrugs of acyclovir: implications for prodrug design.a series of water-soluble dipeptide ester prodrugs of the antiviral acyclovir (acv) were evaluated for their chemical stability, cytotoxicity, and antiviral activity against several strains of herpes simplex-1 and -2, vaccinia, vesicular stomatitis, cytomegalovirus and varicella zoster viruses. acv dipeptide esters were very active against herpetic viruses, independently of the rate at which they liberate the parent drug. their minimum cytotoxic concentrations were above 100 microm and the resul ...200918848738
primary target cells of herpes simplex virus type 1 in the hippocampus.herpes simplex virus type 1 (hsv-1) causes fatal and sporadic encephalitis in human. the encephalitis-survivors frequently suffer from symptoms of memory deficits. it remains unclear how hsv-1 induces tissue damages in memory formation-associated brain tissues such as the hippocampus. in this study, we examined hsv-1 infection in the hippocampus using a rat hsv-1 infection model. we found profound pathological changes in the hippocampus and large numbers of hsv-1 antigen-positive cells in the de ...200818852062
synthesis, antioxidative and antiviral activity of hydroxycinnamic acid amides of thiazole containing amino acid.the synthesis and the biological (antioxidant and antiviral) activities of novel hydroxycinnamic acid amides of a thiazole containing tfa.valine-4-carboxylic acid ethyl ester are reported. the amides have been synthesized from p-coumaric, ferulic and sinapic acids with the corresponding tfa.valine-thiazole-4-carboxylic acid ethyl ester using the coupling reagent n-ethyl-n'-(3-dimethylaminopropyl) carbodiimide hydrochloride (edc) and 4-(dimethylamino) pyridine (dmap) as a catalyst. the antioxidan ...200918853101
noninvasive molecular imaging of hypoxia in human xenografts: comparing hypoxia-induced gene expression with endogenous and exogenous hypoxia markers.tumor hypoxia is important in the development and treatment of human cancers. we have developed a novel xenograft model for studying and imaging of hypoxia-induced gene expression. a hypoxia-inducible dual reporter herpes simplex virus type 1 thymidine kinase and enhanced green fluorescence protein (hsv1-tkegfp), under the control of hypoxia response element (9hre), was stably transfected into human colorectal ht29 cancer cells. selected clones were further enriched by repeated live cell sorting ...200818922936
the p59 oligoadenylate synthetase-like protein possesses antiviral activity that requires the c-terminal ubiquitin-like domain.viral infection of mammalian cells prompts the innate immune system to initiate an antiviral response. the recognition of the virus triggers several antiviral signalling pathways, which among others include the family of 2'-5' oligoadenylate synthetase (oas) proteins. the p59 protein encoded by the oas-like (oasl) gene is an atypical member of the oas family in the sense that it lacks the characteristic 2'-5' oligoadenylate synthetase activity. we decided to investigate the putative antiviral ac ...200818931074
the essential and non-essential genes of bovine herpesvirus 1.bovine herpesvirus 1 (bohv-1) is an economically important pathogen of cattle associated with respiratory and reproductive disease. to further develop bohv-1 as a vaccine vector, a study was conducted to identify the essential and non-essential genes required for in vitro viability. random-insertion mutagenesis utilizing a tn5 transposition system and targeted gene deletion were employed to construct gene disruption and gene deletion libraries, respectively, of an infectious clone of bohv-1. tra ...200818931083
the product of the herpes simplex virus 1 ul7 gene interacts with a mitochondrial protein, adenine nucleotide translocator 2.the herpes simplex virus 1 (hsv-1) ul7 gene is highly conserved among herpesviridae. since the construction of recombinant hsv-1 with a mutation in the ul7 gene has not been reported, the involvement of hsv-1 ul7 in viral replication has been unclear. in this study, we succeeded in generating a ul7 null hsv-1 mutant virus, mt102, and characterized it. our results were as follows. (i) in vero cells, mt102 was replication-competent, but formed smaller plaques and yielded 10- to 100-fold fewer prog ...200818940012
cutting edge: local recall responses by memory t cells newly recruited to peripheral nonlymphoid tissues.infection results in the formation of a circulating effector memory t cell population able to enter peripheral tissues either in the steady state or in response to localized infection. as a consequence, recall is thought to result from a phased response first involving those t cells already at the site of infection followed by the infiltration of memory cells from the wider circulation. we have recently reported that tissue-resident t cells can undergo stimulation and proliferation in response t ...200818941171
[antiviral and immunomodulating activity of polyprenyl phosphates in viral infections].expressed antiviral activity of fortepren (fp) and gamapren (gp), polyprenyl phosphate (ppp)-contaning agents, was demonstrated in experiments on mice infected with the human herpes simplex virus, type 1 (hsv1) or the vernal encephalitis virus (vev). since both the viral infections are of great social significance, the ppp-containing agents should be considered prospective for the medical practice. the experimental data suggested that both the drugs considerably inhibited the vev infectiousness ...200818942418
the two functions of herpes simplex virus 1 icp0, inhibition of silencing by the corest/rest/hdac complex and degradation of pml, are executed in tandem.icp0, an alpha (immediate-early) protein of herpes simplex virus 1, performs at least two key functions. it blocks inhibition of viral-gene expression by interferon, a function dependent on the degradation of the nd10 components pml and sp100 by the ubiquitin ligase expressed by the ring finger (rf), and it blocks silencing of viral dna mediated by the hdac1/2-corest-rest complex. in the latter case, a mutant corest lacking the hdac1 binding site compensates totally or in part for the absence of ...200918945770
the effects of trichostatin a on the oncolytic ability of herpes simplex virus for oral squamous cell carcinoma cells.combining the use of a chemotherapeutic agent with oncolytic virotherapy is a useful way to increase the efficiency of the treatment of cancer. the effect of the histone diacetylase (hdac) inhibitor trichostatin a (tsa) on the antitumor activity of a herpes simplex virus type-1 (hsv-1) mutant was examined in oral squamous cell carcinoma (scc) cells. immunoblotting analysis and immunoflourescence staining revealed that a cytoplasmic nuclear factor-kappab (nf-kappab) component, p65, translocated i ...200918949013
the role of herpes simplex virus-1 thymidine kinase alanine 168 in substrate specificity.herpes simplex virus type 1 (hsv) thymidine kinase (tk) has been widely used in suicide gene therapy for the treatment of cancer due to its broad substrate specificity and the inability of the endogenous human tk to phosphorylate guanosine analogs such as ganciclovir (gcv). the basis of suicide gene therapy is the introduction of a gene that encodes a prodrug-activating enzyme into tumor cells. after administration, the prodrug is selectively converted to a toxic drug by the suicide gene product ...200818949076
structure-function analysis of herpes simplex virus glycoprotein b with fusion-from-without activity.fusion-from-without (ffwo) is the rapid induction of cell fusion by virions in the absence of viral protein synthesis. the combination of two amino acid mutations in envelope glycoprotein b (gb), one in the ectodomain and one in the cytoplasmic tail, can confer ffwo activity to wild type herpes simplex virus (hsv). in this report, we analyzed the entry and cell fusion phenotypes of hsv that contains ffwo gb, with emphasis on the cellular receptors for hsv, nectin-1, nectin-2 and hvem. the abilit ...200818950828
differing roles of inner tegument proteins pul36 and pul37 during entry of herpes simplex virus type 1.studies with herpes simplex virus type 1 (hsv-1) have shown that secondary envelopment and virus release are blocked in mutants deleted for the tegument protein gene ul36 or ul37, leading to the accumulation of dna-containing capsids in the cytoplasm of infected cells. the failure to assemble infectious virions has meant that the roles of these genes in the initial stages of infection could not be investigated. to circumvent this, cells infected at a low multiplicity were fused to form syncytia, ...200918971278
herpes simplex virus type 1 dna is located within alzheimer's disease amyloid plaques.the brains of alzheimer's disease sufferers are characterized by amyloid plaques and neurofibrillary tangles. however, the cause(s) of these features and those of the disease are unknown, in sporadic cases. we previously showed that herpes simplex virus type 1 is a strong risk factor for alzheimer's disease when in the brains of possessors of the type 4 allele of the apolipoprotein e gene (apoe-epsilon4), and that beta-amyloid, the main component of plaques, accumulates in herpes simplex virus t ...200918973185
tumor-specific activity of cellular regulatory elements is down-regulated upon insertion into the herpes simplex virus genome.transcriptional targeting of viral genes is a promising strategy to achieve tumor-specific replication of oncolytic viruses. due to its natural tropism, herpes simplex virus type 1 (hsv-1) may be an ideal tool for oncolytic therapy of brain tumors such as malignant glioblastoma. to study whether glioma-specific gene expression can be accomplished within the hsv-1 genome, four cellular regulatory elements were exemplarily studied. whereas the human telomerase reverse transcriptase (htert) and sur ...200818979278
[facial nerve paresis]. 200818983050
magnetic resonance and diffusion-weighted imaging findings of herpes simplex encephalitis.herpes simplex encephalitis (hse) is a rare, life-threatening disease. this paper draws attention to the role of imaging in early hse diagnosis. five consecutive patients diagnosed with hse (type 1) between june 2005 and june 2006 (three males, two females, mean age 44 [range 16-68] years) were included in this retrospective study. computed tomography, conventional magnetic resonance imaging (mri) sequences and diffusion-weighted imaging (dwi) were obtained for each patient. apparent diffusion c ...200818983763
ras signaling influences permissiveness of malignant peripheral nerve sheath tumor cells to oncolytic herpes.lack of expression of neurofibromin in neurofibromatosis 1 and its lethal derivative, malignant peripheral nerve sheath tumors (mpnsts), is thought to result in the overactivation of the ras signaling pathway. our previous studies have shown that cells with overactivation in the ras pathway are more permissive to infection with herpes simplex virus 1 and its mutant version r3616. in this study, we show that among five different mouse mpnst cell lines, only the ones with elevated levels of ras si ...200818988803
[specific cellular immune system and a human herpes virus infection in various forms of tubercular process].tuberculosis (tb) is one of the most common infective diseases in history. in industrialized nations tb was well on its way to becoming extinct, however, tb rates started increasing again in the majority of developed countries today. there is a need to further understanding the role of a human herpes virus (hhv) in development and prognosis of tb. the goal of research was to study a condition of the specific immune system, frequency of activization of a hhv infection of 1 type and presence of in ...200818997252
high-level expression of glycoprotein d by a dominant-negative hsv-1 virus augments its efficacy as a vaccine against hsv-1 infection.using the t-rex (invitrogen, carlsbad, ca) gene switch technology, we previously generated a dominant-negative herpes simplex virus (hsv)-1 recombinant, cj83193, capable of inhibiting its own replication as well as that of wild-type hsv-1 and hsv-2. it has been further demonstrated that cj83193 is an effective vaccine against hsv-1 infection in a mouse ocular model. to ensure its safety and augment its efficacy, we generated an improved cj83193-like hsv-1 recombinant, cj9-gd, which contains a de ...200919005489
loop ii of dna polymerase beta is important for discrimination during substrate binding.loop ii of dna polymerase beta (pol beta) consists of 14 amino acid residues and is highly flexible and solvent exposed. previous research from our laboratory has shown that this loop is important for polymerase activity and fidelity. in the study presented here, we demonstrate that a shortened five amino acid residue loop compromises the fidelity of pol beta. this five-residue loop, termed eneyp, induces one base frameshift errors and a-c transversions within a specific sequence context. we dem ...200919013261
efficient nuclear export of herpes simplex virus 1 transcripts requires both rna binding by icp27 and icp27 interaction with tap/nxf1.herpes simplex virus 1 (hsv-1) regulatory protein icp27 has been reported to bind viral rna and to interact with the nuclear export adaptor aly/ref and the major cellular mrna nuclear export receptor tap/nxf1. using in situ hybridization and in vitro export assays, we show here that poly(a)(+) rna was retained in the nucleus of cells infected with viral icp27 mutants that either cannot bind rna or that do not interact with tap/nxf1. microarray analysis of nuclear and cytoplasmic rna fractions de ...200919019956
[an experimental study on targeting suicide gene therapy for lung cancer with hsv-tk driven by htert promoter].to study the approach of targeting expression of suicide gene hsv-tk driven by human telomerase catalytic subunit (htert) promoter in lung cancer cells, and to investigate inhibitory effect of hsv-tk/gcv driven by htert promoter on proliferation of lung cancer cell line a549 in vitro and in vivo.200819024294
delivery of interferon-gamma by an adenovirus vector blocks herpes simplex virus type 1 reactivation in vitro and in vivo independent of rnase l and double-stranded rna-dependent protein kinase pathways.hsv-1 is a significant human pathogen that can result in the loss of sight as a result of episodic reactivation of latent virus from sensory ganglion neurons. in this study the potential efficacy of anti-viral cytokine expression in preventing latent virus reactivation was investigated. both type i (ifn-beta) and type ii (ifn-gamma) ifn transgene expression following transduction of trigeminal ganglion explant cultures significantly reduced the incident of hsv-1 reactivation that in the case of ...200919042034
dynamic of migration of hsv-1 from a medullary pronociceptive centre: antinociception by overexpression of the preproenkephalin transgene.herpes simplex virus type 1 (hsv-1) vectors are known to inhibit nociceptive transmission at the spinal cord after peripheral applications. similar approaches may also be useful when applied at the supraspinal pain control system as the system includes pronociceptive (facilitatory) components. we performed a study aimed to analyse the migration of hsv-1 along with the inhibition of pronociception from the medullary dorsal reticular nucleus (drt), a major facilitatory component of the supraspinal ...200819046388
nuclear import of hsv-1 dna polymerase processivity factor ul42 is mediated by a c-terminally located bipartite nuclear localization signal.the polymerase accessory protein of the human herpes simplex virus type 1 (hsv-1) dna polymerase ul42 plays an essential role in viral replication, conferring processivity to the catalytic subunit ul30. we show here that ul42 is imported to the nucleus of living cells in a ran- and energy-dependent fashion, through a process that requires a c-terminally located bipartite nuclear localization signal (ul42-nlsbip; pttkrgrsggedaradalkkpk(413)). moreover cytoplasmic mutant derivatives of ul42 lackin ...200819053255
detection of herpesviruses and periodontal pathogens in subgingival plaque of patients with chronic periodontitis, generalized aggressive periodontitis, or gingivitis.herpesviruses may be related to the etiology of aggressive periodontitis (agp) and chronic periodontitis (cp) by triggering periodontal destruction or by increasing the risk for bacterial infection. this case-control study evaluated the presence of herpes simplex virus type i (hsv-1), epstein-barr virus type i (ebv-1), human cytomegalovirus (hcmv), aggregatibacter actinomycetemcomitans (previously actinobacillus actinomycetemcomitans), porphyromonas gingivalis, prevotella intermedia, and tannere ...200819053922
a serological survey of herpes simplex virus type 1 and 2 immunity in pregnant women at labor stage in tehran, iran.this study was carried out to determine the prevalence of neutralizing antibodies to herpes simplex virus type 1 (hsv-i) and type 2 (hsv-2) in pregnant women at labor stage. blood samples from umbilical cord of four hundred women aging 16 to 40 years at labor stage were collected. after sera separation quantity of anti hsv-1 and hsv-2 antibodies were measured by serum neutralization test. antibody quantification was assayed by two fold dilution of sera (from 1/2 to 1/256) with 500 tissue culture ...200719070003
herpes simplex virus type 1 thymidine kinase sequence fused to the lacz gene increases levels of {beta}-galactosidase activity per genome of high-capacity but not first-generation adenoviral vectors in vitro and in vivo.increased transgene expression per vector genome is an important goal in the optimization of viral vectors for gene therapy. herein we demonstrate that herpes simplex virus type 1 (hsv1) thymidine kinase (tk) gene sequences (1,131 bp) fused to the 3' end of lacz increase transgene expression from high-capacity adenoviral vectors (hcad), but not from first-generation (ad) vectors. the woodchuck hepatitis virus posttranscriptional regulatory element (wpre), in contrast, increased transgene express ...200919073729
[analgesic effect of intrathecal injection of herpes simplex virus type i amplicon vector-mediated human preproenkephalin gene on chronic neuropathic pain: experiment with rats].to investigate the antinociceptive effect of intrathecal (it) injection of herpes simplex virus type i (hsv-1) amplicon vector-mediated hppe on chronic neuropathic pain.200819080437
acute retinal necrosis in primary herpes simplex virus type i infection.here we report the case of an immunocompetent 8-year-old child who developed acute retinal necrosis concomitant with a primary herpes simplex virus type i infection. ocular inflammation changed along with the development of a specific antibody titer in the serum. this evidence suggests that the immune response of the host can significantly modulate the clinical aspect of the ocular infection.200919106778
host responses to wild-type and attenuated herpes simplex virus infection in the absence of stat1.humans and mice lacking the interferon signaling molecule stat1 are sensitive to a variety of pathogens due to their presumed inability to mount a strong innate immune response. the herpes simplex virus type 1 (hsv-1) virion host shutoff (vhs) protein is a multifunctional immunomodulator that counteracts the innate immune response and viruses lacking vhs are attenuated and effective live vaccines in animal models. to investigate the interplay of viruses with an immunocompromised host, we perform ...200919109391
american college health association annual pap test and sexually transmitted infection survey: 2006.the authors describe the cervical cytology and sexually transmitted infection (sti) testing patterns of us college health centers.200919114378
hsv immune complex (hsv-igg: ic) and hsv-dna elicit the production of angiogenic factor vegf and mmp-9.angiogenesis and inflammatory mediators are critical pathogenic factors in herpetic stromal keratitis (hsk). since disease progresses without infectious virus, hsv-dna and hsv-igg complexes (hsv-ic) may contribute to hsk by triggering these factors. production of vegf and mmp-9 was studied in vitro using corneal epithelial cells (hce), fibroblasts (hcrf) and macrophages (thp-1). vegf was elevated in hcrf and thp-1 following treatment with hsv-dna and hsv-ic. mmp-9 was elevated in thp-1 but not i ...200919115032
hsv-1 infection through inhibitory receptor, pilralpha.paired receptors that consist of highly related activating and inhibitory receptors are widely involved in the regulation of immune response. several viruses that persistently infect hosts possess genes that encode ligands for inhibitory receptors in order to escape from host immune system. herpes simplex virus type 1 (hsv-1) is one of the viruses that cause persistent infection. here, we found that hsv-1-infected cells express a ligand for paired immunoglobulin like-type 2 receptor (pilr)alpha, ...200819122386
kinetics of major histocompatibility class i antigen presentation in acute infection.ag presentation within the regional lymph node is crucial for the initiation of cd8+ t cell responses following viral infection. the magnitude and quality of the cd8+ t cell response are regulated by the interplay between the size of the apc population and duration of ag presentation. to understand how these parameters are finely regulated during an immune response, we have investigated the dynamics of ag presentation in influenza a virus and hsv-1 infection. in both infections, apc production w ...200919124733
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