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technology evaluation: nv-1020, medigene.nv-1020 is a recombinant oncolytic hsv-based virus, in development by medigene (formerly neurovir) for the potential treatment of cancer. the therapy is currently undergoing phase ii clinical trials.200516121703
stable levels of long-term transgene expression driven by the latency-associated transcript promoter in a herpes simplex virus type 1 vector.previous gene transfer studies of the herpes simplex virus type 1 (hsv-1) using the latency-associated transcript (lat) promoter have reported a decrease in transgene expression in the brain over time, but the extent of this decrease has not been measured and it is unknown if expression eventually stabilizes. we examined lat promoter-mediated transgene expression in the mouse brain for 1 year following intracranial injection with a hsv-1 vector expressing human beta-glucuronidase (gusb). the vec ...200516122987
effect of resveratrol on herpes simplex virus vaginal infection in the mouse.resveratrol (3,5,4'-trihydroxystilbene) is a natural component of certain foods, such as grapes, that, when topically applied, has been shown to limit hsv-1 lesion formation in the skin of mice [antiviral res. 61:19-26, 2004]. to determine if it is active on genital hsv infection, the vagina of mice were infected with hsv-2 or hsv-1 and treated with a cream formulation of resveratrol. mice were evaluated daily for extravaginal disease and vaginal swabs were taken regularly and assayed for infect ...200516125258
structural analysis and antiviral activity of a sulfated galactan from the red seaweed schizymenia binderi (gigartinales, rhodophyta).aqueous extraction of gametophytic schizymenia binderi afforded a polysaccharide composed of galactose and sulfate groups in a molar ratio of 1.0:0.89 together with uronic acids (6.8 wt%) and minor amounts of other neutral sugars. alkali-treatment of the polysaccharide afforded a polysaccharide devoid of 3,6-anhydrogalactose. 13c nmr spectroscopy of the desulfated alkali-treated polysaccharide showed a backbone structure of alternating 3-linked beta-d-galactopyranosyl and 4-linked alpha-galactop ...200516125685
[is prevention of reactivation of herpes simplex 1 virus necessary in cosmetic surgery and dermatological procedures?]. 200516130033
the role of icp0-null hsv-1 and interferon signaling defects in the effective treatment of breast adenocarcinoma.oncolytic viruses that selectively replicate in cancer cells have been described for over 50 years. despite the observation by several groups that multimutated herpes simplex type 1 vectors are oncolytic in a variety of murine tumor models, the oncolytic potential of icp0 null mutants has not been described. this study characterizes a novel second-generation oncolytic herpes simplex type 1 vector null for the icp0 gene. we tested three mutant viruses and found that all were selectively cytotoxic ...200516140040
in vivo kinetics of gitr and gitr ligand expression and their functional significance in regulating viral immunopathology.this report evaluates the role of interaction between glucocorticoid-induced tumor necrosis factor receptor (gitr) and gitr ligand (gitr-l) in the immuno-inflammatory response to infection with herpes simplex virus (hsv). both gitr and gitr-l were transiently upregulated after ocular hsv infection, on antigen-specific t cells and antigen-presenting cells, respectively, in the draining lymph node (dln). in addition, virus-specific t-cell responses in the dln and spleen were enhanced by anti-gitr ...200516140769
the extracellular domain of herpes simplex virus ge is indispensable for efficient cell-to-cell spread: evidence for ge/gi receptors.herpes simplex virus (hsv) spreads rapidly and efficiently within epithelial and neuronal tissues. the hsv glycoprotein heterodimer ge/gi plays a critical role in promoting cell-to-cell spread but does not obviously function during entry of extracellular virus into cells. thus, ge/gi is an important molecular handle on the poorly understood process of cell-to-cell spread. there was previous evidence that the large extracellular (et) domains of ge/gi might be important in cell-to-cell spread. fir ...200516140775
a herpes simplex virus type 1 mutant expressing a baculovirus inhibitor of apoptosis gene in place of latency-associated transcript has a wild-type reactivation phenotype in the mouse.the latency-associated transcript (lat) is essential for the wild-type herpes simplex virus type 1 (hsv-1) high-reactivation phenotype since lat- mutants have a low-reactivation phenotype. we previously reported that lat can decrease apoptosis and proposed that this activity is involved in lat's ability to enhance the hsv-1 reactivation phenotype. the first 20% of the primary 8.3-kb lat transcript is sufficient for enhancing the reactivation phenotype and for decreasing apoptosis, supporting thi ...200516160155
reciprocal activities between herpes simplex virus type 1 regulatory protein icp0, a ubiquitin e3 ligase, and ubiquitin-specific protease usp7.herpes simplex virus type 1 (hsv-1) regulatory protein icp0 stimulates lytic infection and the reactivation of quiescent viral genomes. these roles of icp0 require its ring finger e3 ubiquitin ligase domain, which induces the degradation of several cellular proteins, including components of promyelocytic leukemia nuclear bodies and centromeres. icp0 also interacts very strongly with the cellular ubiquitin-specific protease usp7 (also known as hausp). we have shown previously that icp0 induces it ...200516160161
valacyclovir to expedite the clearance of recurrent herpes gladiatorum.to determine if valacyclovir usage expedites the clearance of recurrent herpes gladiatorum (hg) in wrestlers.200516162997
immunity in latent herpes simplex virus infection.immune responses against productive herpes simplex virus 1 (hsv-1) and/or herpes simplex virus 2 (hsv-2) (hsv) infection together with associated immune escape mechanisms are to a great degree understood. due to a limited rna expression and lacking a convincing evidence for production of virus proteins during latency, hsv in latently infected neurons had been for a long period considered invisible to immune system. this review analyzes currently accumulating data indicating an important role of ...200516178513
adenovirus-directed ocular innate immunity: the role of conjunctival defensin-like chemokines (ip-10, i-tac) and phagocytic human defensin-alpha.adenovirus (ad), a major cause of viral conjunctivitis worldwide, is controlled initially by the innate immune response on the ocular surface. in the present study, cultured human conjunctival epithelial cells were used to identify host genes responsive to infection by a clinical isolate of ad5, and the antiviral activity of some of their peptide products was investigated.200516186347
identification and functional evaluation of cellular and viral factors involved in the alteration of nuclear architecture during herpes simplex virus 1 infection.herpes simplex virus 1 (hsv-1) replicates in the nucleus of host cells and radically alters nuclear architecture as part of its replication process. replication compartments (rcs) form, and host chromatin is marginalized. chromatin is later dispersed, and rcs spread past it to reach the nuclear edge. using a lamin a-green fluorescent protein fusion, we provide direct evidence that the nuclear lamina is disrupted during hsv-1 infection and that the ul31 and ul34 proteins are required for this. we ...200516188986
virus infection switches tlr-3-positive human neurons to become strong producers of beta interferon.to study the capacity of human neurons to mount innate immunity responses to viral infections, we infected cells of a human postmitotic neuron-derivative cell line, nt2-n, with rabies virus (rabv) and herpes simplex type 1 (hsv-1). changes in neuronal gene expression were analyzed by use of affymetrix microarrays. applying a twofold cutoff, rabv increased the transcription of 228 genes, and hsv-1 increased the transcription of 263 genes. the most striking difference between the two infections co ...200516188991
characterization of hpv-16 e6 dna vaccines employing intracellular targeting and intercellular spreading strategies.human papillomavirus (hpv) e6 and e7 are consistently expressed and are responsible for the malignant transformation of hpv-associated lesions. thus, e6 and e7 represent ideal targets for therapeutic hpv vaccine development. we have previously used the gene gun approach to test several intracellular targeting and intercellular spreading strategies targeting hpv-16 e7. these strategies include the use of the sorting signal of lysosome-associated membrane protein (lamp-1), mycobacterium tuberculos ...200516200349
immune control of hsv-1 latency.a hallmark of the herpes family of viruses is their ability to cause recurrent disease. upon primary infection, herpes simplex virus (hsv) establishes a latent infection in sensory neurons that persists for the life of the individual. reactivation of these latent viral genomes with virion formation is the source of virus for most hsv recurrent disease. this review details recent exciting findings supporting a role for the host immune system, particularly cd8+ t cells in maintaining hsv-1 in a la ...200516212525
seroprevalence of herpes simplex virus 1 and 2 and correlates of infection in israel.the prevalence of infections with herpes viruses 1 and 2 (hsv1 and hsv2) have significantly changed in the developed countries during the last three decades. this study provides up-to-date estimates of hsv-1 and hsv-2 seroprevalence and information on the correlates of infection in a representative sample of the israeli population.200616213591
serum-resistant gene transfer to oral cancer cells by metafectene and genejammer: application to hsv-tk/ganciclovir-mediated cytotoxicity.cationic lipids and polyamines have been used as non-viral gene transfer reagents, both in vitro and in vivo. one of the limitations to their use in vivo is the inhibition of gene delivery by serum. we showed previously that, in the absence of serum, relatively high cytotoxicity in oral cancer cell lines could be achieved via transfection of the herpes simplex virus thymidine kinase (hsv-tk) gene followed by treatment with ganciclovir (gcv), despite the low efficiency of transfection (konopka et ...200516217556
[detection of sexually transmitted pathogens in patients with hematospermia].although the current literature attributes most cases of hematospermia to an infectious agent, identification of the specific pathogens involved has been limited.200516218534
herpes simplex virus type 1 immediate-early protein icp0 diffuses out of infected rabbit corneas.herpes stromal keratitis (hsk) results from infection of herpes simplex virus (hsv) in the cornea. recurrent hsv infection is a leading cause of corneal scarring and visual loss. although it is generally thought that hsk is the result of an immune response to one or more viral proteins, no viral proteins have been detected in hsk corneas. thus, the viral proteins involved in hsk, if any, remain undetermined. in contrast, it is reported here that when hsk corneal buttons from latently infected ra ...200516227219
characterization of a highly glycosylated form of the human cytomegalovirus hla class i homologue gpul18.human cytomegalovirus (hcmv) gpul18 is a hla class i (hla-i) homologue with high affinity for the inhibitory receptor lir-1/ilt2. the previously described 67 kda form of gpul18 is shown here to be sensitive to endoglycosidase-h (endoh). a novel form of gpul18 with a molecular mass of approximately 160 kda and resistance to endoh was identified in cells infected with hcmv strain ad169 or the low passage hcmv isolates merlin and toledo. the 67 kda endoh-sensitive gpul18 glycoform was detected earl ...200516227221
herpes simplex virus type 1 glycoprotein e is required for axonal localization of capsid, tegument, and membrane glycoproteins.herpes simplex virus type 1 (hsv-1) glycoprotein e (ge) promotes cell-to-cell spread at basolateral surfaces of epithelial cells, but its activity in neurons is less clear. we used the mouse retina infection model and neuronal cell cultures to define the spread phenotype of ge mutant viruses. wild-type (wt) and ge-null (ns-genull) viruses both infected retina ganglion cell neurons; however, ns-genull viral antigens failed to reach the optic nerve, which indicates a defect in axonal localization. ...200516227258
herpes simplex keratitis misdiagnosed as rheumatoid arthritis-related peripheral ulcerative keratitis.to report 2 cases of herpes simplex keratitis misdiagnosed as rheumatoid arthritis (ra)-related peripheral ulcerative keratitis (puk), where isolation of the herpes simplex virus (hsv) led to a complete modification in management.200516227854
assessment of viral and non-viral gene transfer into adult rat brains using hsv-1, calcium phosphate and pei-based methods.cns gene transfer could provide new approaches to the modelling of neurodegenerative diseases and devising potential therapies. one such disorder is parkinson's disease (pd), in which dysfunction of several different metabolic processes has been implicated. here we review the literature on gene transfer systems based on herpes simplex virus type 1 (hsv-1) and non-viral polyethyleneimine (pei) and calcium phosphate nanoparticle methods. we also assess the usefulness of various cns gene delivery m ...200516228947
hsv-1-based amplicon vectors: design and applications.amplicons are defective, helper-dependent herpes simplex virus type 1 (hsv-1)-based vectors able to convey more than 100 kbp of foreign dna to the nucleus of mammalian cells. this unique feature make amplicons very appealing for preventive or therapeutic gene transfer requiring the transduction of very large pieces of dna, as well as for upstream fundamental studies, such as functional genomics. several recent achievements in amplicon technology have allowed to produce relatively large amounts o ...200516231049
synthesis, physicochemical properties and antiviral activities of ester prodrugs of ganciclovir.the purpose of this study was to synthesize a series of diester prodrugs of ganciclovir (gcv), for improving ocular and oral bioavailability and therapeutic activity. solubility, logp, ph stability profile, in vitro antiviral activity, cytotoxicity, inhibition profile and ocular tissue hydrolysis of the gcv prodrugs were measured. val-val-gcv and val-gly-gcv diesters were found to exhibit greater aqueous stability compared to val-gcv and gly-val-gcv while ocular tissue hydrolysis demonstrated va ...200516242278
herpes encephalitis preceded by ipsilateral vestibular neuronitis.a 74-year-old woman developed vertigo and jerk nystagmus to the left with normal cerebral imaging. three days later she developed fever, altered mental state and left medial temporal lobe hypodensity, confirmed on lumbar puncture to be due to herpes simplex type 1 encephalitis. we propose that the patient had vestibular neuronitis caused by hsv-1 that progressed to ipsilateral temporal lobe encephalitis.200516246566
binding of herpes simplex virus-1 us11 to specific rna sequences.herpes simplex virus-1 us11 is a rna-binding protein with a novel rna-binding domain. us11 has been reported to exhibit sequence- and conformation-specific rna-binding, but the sequences and conformations important for binding are not known. us11 has also been described as a double-stranded rna (dsrna)-binding protein. to investigate the us11-rna interaction, we performed in vitro selection of rna aptamers that bind us11 from a rna library consisting of >10(14) 80 base sequences which differ in ...200516246910
transplantation of amniotic membrane in murine herpes stromal keratitis modulates matrix metalloproteinases in the cornea.to study matrix metalloproteinases (mmp) and tissue inhibitors of metalloproteinases (timp) in the corneas from mice with ulcerative herpes stromal keratitis (hsk) treated with amniotic membrane transplantation (amt).200516249483
enzymatic redesigning of biologically active heparan sulfate.heparan sulfate carries a wide range of biological activities, regulating blood coagulation, cell differentiation, and inflammatory responses. the sulfation patterns of the polysaccharide are essential for the biological activities. in this study, we report an enzymatic method for the sulfation of multimilligram amounts of heparan sulfate with specific functions using immobilized sulfotransferases combined with a 3'-phosphoadenosine 5'-phosphosulfate regeneration system. by selecting appropriate ...200516260789
5-fluorouracil and gemcitabine potentiate the efficacy of oncolytic herpes viral gene therapy in the treatment of pancreatic cancer.oncolytic herpes viruses are attenuated, replication-competent viruses that selectively infect, replicate within, and lyse cancer cells and are highly efficacious in the treatment of a wide variety of experimental cancers. the current study seeks to define the pharmacologic interactions between chemotherapeutic drugs and the oncolytic herpes viral strain nv1066 in the treatment of pancreatic cancer cell lines. the human pancreatic cancer cell lines hs 700t, panc-1, and mia paca-2 were treated in ...200516269377
mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging.the aim of this study was to assess the efficacy human mesenchymal stem cells (hmsc) for targeting microscopic tumors and suicide gene or cytokine gene therapy. immunodeficient mice were transplanted s.c. with human colon cancer cells of ht-29 inv2 or ccs line, and 3 to 4 days later, i.v. with "tracer" hmscs expressing herpes simplex virus type 1 thymidine kinase (hsv1-tk) and enhanced green fluorescent protein (egfp) reporter genes. subsequently, these tumors were examined for specificity and m ...200516278396
herpes simplex virus 1 immediate-early and early gene expression during reactivation from latency under conditions that prevent infectious virus production.the program of gene expression exhibited by herpes simplex virus during productive infection of cultured cells is well established; however, less is known about the regulatory controls governing reactivation from latency in neurons. one difficulty in examining gene regulation during reactivation lies in distinguishing between events occurring in initial reactivating cells versus events occurring in secondarily infected cells. thus, two inhibitors were employed to block production of infectious v ...200516282451
the neuronal host cell factor-binding protein zhangfei inhibits herpes simplex virus replication.during lytic infection in epithelial cells the expression of herpes simplex virus type 1 (hsv-1) immediate-early (ie) genes is initiated by a multiprotein complex comprising the virion-associated protein vp16 and two cellular proteins, host cellular factor (hcf) and oct-1. oct-1 directly recognizes taatgarat elements in promoters of ie genes. the role of hcf is not clear. hsv-1 also infects sensory neurons innervating the site of productive infection and establishes a latent infection in these c ...200516282471
development of the loop-mediated isothermal amplification method for rapid detection of cytomegalovirus dna.cytomegalovirus (cmv) loop-mediated isothermal amplification (lamp) was performed on dna extracted from cmv (ad-169)-, herpes simplex virus (hsv) 1 (kos)-, hsv-2 (186)-, varicella-zoster virus (oka-vaccine)-, human herpesvirus (hhv)-6 a (u1102)-, hhv-6 b (z29)-, and hhv-7 (rk)-infected cells. although amplified cmv demonstrated typical ladder patterns, no lamp product was detected in reactions performed with other viral dnas. the sensitivity of the cmv lamp was 500 copies/tube, as determined by ...200616289345
intratypic variations among thai herpes simplex virus (hsv) isolates determined by restriction fragment length polymorphism (rflp) analysis.whole genomic polymorphisms for 20 hsv-1 and 20 hsv-2 isolates from thai patients were analyzed by means of restriction fragment length polymorphism (rflp) analysis using 4 restriction endonucleases: bamhi, kpnl, hindiii, and ecori. variations in cleavage sites among the hsv-1 and hsv-2 isolates were compared to the cleavage patterns of standard hsv-1 strain kos and hsv-2 strain baylor 186. although 70% of hsv-1 isolates with bamhi digestion, 50% with kpnl, 75% with hindiii and 70% with ecori di ...200516295545
broad spectrum antimicrobial activity of leukocyte extracts from the american alligator (alligator mississippiensis).leukocytes were isolated from whole blood of wild alligators by differential sedimentation. the leukocytes were disrupted in 5% acoh and the crude extracts processed by ultrafiltration. the extracts were subjected to solvent exchange (0.1% acoh) and the fraction that contained macromolecules between 1 and 10 kda were subjected to further analyses. the acid extracts of the alligator leukocytes exhibited substantial antimycotic activities against six of eight species of candida yeast tested. in ad ...200616298430
to replicate or not to replicate: achieving selective oncolytic virus replication in cancer cells through translational control.to ensure that their mrnas are translated and that the viral proteins necessary for assembling the next generation of infectious progeny are produced, viruses must effectively seize control of the translational machinery within their host cells. in many cases, the ability to productively engage host translational components can determine if a given cell type can support viral replication, illustrating the critical importance of this task in the viral life cycle. failure to interface properly wit ...200516299530
a deubiquitinating activity is conserved in the large tegument protein of the herpesviridae.the largest tegument protein of herpes simplex virus 1 (hsv-1), ul36, contains a novel deubiquitinating activity embedded in it. all members of the herpesviridae contain a homologue of hsv-1 ul36, the n-terminal segments of which show perfect conservation of those residues implicated in catalysis. for murine cytomegalovirus and epstein-barr virus, chosen as representatives of the beta- and gammaherpesvirus subfamilies, respectively, we here show that the homologous modules indeed display deubiqu ...200516306630
a novel pharmacological approach to herpes virus infections. 198916312792
immunohistochemical diagnosis of herpetic gingivostomatitis and its treatment with acyclovir. 198916312796
triple gene-deleted oncolytic herpes simplex virus vector double-armed with interleukin 18 and soluble b7-1 constructed by bacterial artificial chromosome-mediated system.conditionally replicating herpes simplex virus type 1 (hsv-1) vectors are promising therapeutic agents for cancer. certain antitumor functions may be added to oncolytic activities of recombinant hsv-1 vectors by inserting transgenes into the viral genome. because conventional homologous recombination techniques had required time-consuming processes to create "armed" oncolytic hsv-1 vectors, we established an innovative construction system using bacterial artificial chromosome and two recombinase ...200516322208
[mesenchymal dysplasia of heart valves, cystic medianecrosis of the aorta and herpetic infection].histologic and immunohistochemical studies (use of antibodies for viruses of herpes simplex type 1 and 2, desmin, vimentin, sma as well as polymerase chain reaction to dna of viruses of herpes simplex) were made on the material of the valves taken from 1326 patients with valvular heart disease, the ascending aorta of 30 patients with aneurysm, valves of 35 deceased patients without cardiovascular pathology. as a result, expression of viruses of herpes simplex type 1 and/or 2 was found in all cas ...200516323474
differential susceptibility of equine and mouse brain microvascular endothelial cells to equine herpesvirus 1 infection.equine herpesvirus 1 (ehv-1) shows endotheliotropism in the central nervous system (cns) of infected horses. however, infection of endothelial cells has not been observed in the cns of infected mice. to explore the basis for this difference in endotheliotropism, we compared the susceptibility of equine brain microvascular endothelial cells (ebmecs) and mouse brain microvascular endothelial cells (mbmecs) to ehv-1 infection. the kinetics of viral growth in ebmecs was typical of a fully productive ...200616328147
pathogenesis of herpes simplex hepatitis in macrophage-depleted mice: possible involvement of tumor necrosis factor-alpha and inducible nitric oxide synthase in massive apoptosis.massive liver cell death provoked in silica-treated mice subsequently infected with herpes simplex virus (hsv)-1 is very similar pathohistologically to the cell death observed in human fulminant hepatitis. previously, we have shown this liver cell death to be extensive apoptosis. in the present study, we examined various factors related to liver damage patho- and immunologically, as well as by reverse transcription-polymerase chain reaction. tumor necrosis factor (tnf)-alpha, inducible nitric ox ...200516333916
antiherpetic activities of flavonoids against herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) in vitro.flavonoids, a group of low molecular weight phenylbenzopyrones, have various pharmacological properties including antioxidant, anticancer, bactericidal, and anti-inflammatory. we carried out anti-herpetic assays on 18 flavonoids in five classes and a virus-induced cytopathic effect (cpe) inhibitory assay, plaque reduction assay, and yield reduction assay were performed. when flavonoids were applied at various concentrations to vero cells infected by hsv-1 and 2, most of the flavonoids showed inh ...200516350858
point mutations in herpes simplex virus type 1 oril, but not in oris, reduce pathogenesis during acute infection of mice and impair reactivation from latency.in vitro studies of herpes simplex virus type 1 (hsv-1) viruses containing mutations in core sequences of the viral origins of dna replication, oril and oris, that eliminate the ability of these origins to initiate viral-dna synthesis have demonstrated little or no effect on viral replication in cultured cells, leading to the conclusion that the two types of origins are functionally redundant. it remains unclear, therefore, why origins that appear to be redundant are maintained evolutionarily in ...200616352568
the herpes simplex virus type 1 vhs-ul41 gene secures viral replication by temporarily evading apoptotic cellular response to infection: vhs-ul41 activity might require interactions with elements of cellular mrna degradation machinery.we have previously shown that herpes simplex virus type 1 (hsv-1) infection is associated with early destabilization/degradation of infected cell mrnas and consequent shutoff of host protein synthesis by the activity of the virion-associated host shutoff (vhs) ul41 protein. wild-type (wt) virus destabilized/degraded the housekeeping beta-actin and alpha-tubulin mrnas as well host stress functions, like the heat shock 70 protein induced postinfection. vhs mutants did not degrade the mrnas. elabor ...200616352574
synthesis and antiviral evaluation of novel 4'-hydroxymethyl branched thioapiosyl nucleosides.in this study, we synthesized novel 4'-hydroxymethyl branched thioapiosyl nucleosides. the thioapiosyl sugar moiety was constructed using sequential ozonolysis and reduction. the natural bases (uracil, thymine, cytosine, and adenine) were efficiently coupled using the vorbrüggen glycosyl condensation procedure (persilyated base and tmsotf). the antiviral activities of the synthesized compounds were evaluated against hiv-1, hsv-1, hsv-2, and hcmv. compound 19 showed moderate anti-hiv activity (ec ...200516353276
role of mucosal immunity in preventing genital herpes infection.the female genital tract is immunologically unique because it must be tolerant to spermatozoa, pregnancy, and vaginal flora, but also protect the host from pathogen challenge. the mucosal response to herpes simplex viruses (hsv), a major cause of genital ulcerative disease and critical co-factor in the hiv/aids epidemic, is complex and consists of the normally acidic vaginal environment, constitutively secreted and induced antimicrobial peptides, complement, and cellular responses mediated by ep ...200516359226
[synthesis and antiviral activity of new 5-substituted 2'-deoxyuridine derivatives].new 5-azole- and 5-oxime-substituted analogues of 2'-deoxyuridine are synthesized. the analogues with azole ring manifest low toxicities and antiherpetic activities on vero cell culture, the imidazole derivative being the most active. the inhibitory effects of oximes of 5-formyl-deoxyuridine are comparable with those of the azole-containing nucleoside analogues, although their cytotoxicities are found to be higher; oxime of 5-formyldeoxyuridine is particularly toxic. the nucleoside analogues syn ...200516363134
acute limbic encephalitis: a new entity?clinical cases similar to herpes simplex virus (hsv) encephalitis have accumulated in japan. detailed examinations have failed to demonstrate hsv infection. recently, these cases have been named "non-herpetic acute limbic encephalitis". only a single autopsy case was so far reported in an abstract form, because many cases showed a good prognosis. the case presented here was that following fever, a 59-year-old woman developed disturbance of consciousness and uncontrollable generalized seizures. b ...200616364542
dipeptide monoester ganciclovir prodrugs for treating hsv-1-induced corneal epithelial and stromal keratitis: in vitro and in vivo evaluations.the aim of this study was to evaluate a series of dipeptide monoester ganciclovir (gcv) prodrugs with the goal of improving ocular bioavailability of gcv from topical ophthalmic solutions.200516386088
interstitial cystitis and infectious agents.interstitial cystitis (ic) is a syndrome consisting of severe refractory bladder symptoms of unknown etiology. the disease tends to affect caucasian women with a mean age of 40 years, with 25% of patients under the age of 30. few population based epidemiological studies of ic have been performed. we analyzed a case of interstitial cystitis in a 42-year-old non-smoker woman. in two biopsy samples the presence of viral dna of human polyomavirus bk (bkv), human herpes virus type 1 and type 2 (hhv- ...200516388730
fusion of the human immunodeficiency virus type 1 tat protein transduction domain to thymidine kinase increases bystander effect and induces enhanced tumor killing in vivo.the clinical success of suicide gene therapy using herpes simplex virus type 1 thymidine kinase (tk) is largely dependent on the capacity of this enzyme to effectively induce the death of bystander cells. we have shown that fusion of tk to an 11-amino acid peptide from the basic domain of the human immunodeficiency virus type 1 tat protein (tat11) imparts cell membrane-translocating ability to the enzyme and significantly increases its cytotoxic activity. here we report on the efficacy of this s ...200516390270
synthesis and antiviral evaluation of cyclic and acyclic 2-methyl-3-hydroxy-4-pyridinone nucleoside derivatives.a series of cyclic and acyclic nucleoside analogues derived from 3-hydroxy-4-pyridinone were synthesized using the vorbrüggen reaction. iron chelation studies, and antiviral evaluation against a broad panel of viruses, were performed. the pk(a) value of ligand 25 and the stability constant of the corresponding iron(iii) complex were compared to those of deferiprone. the pfe(3+) values were found to be similar. some compounds showed moderate activity against both wild-type hsv-1 and hsv-2, as wel ...200616392791
evaluation of antiviral activity of compounds isolated from ranunculus sieboldii and ranunculus sceleratus.nineteen compounds isolated from ranunculus sieboldii and ranunculus sceleratus were tested for inhibitory effects on hepatitis b virus (hbv) and herpes simplex virus type-1 (hsv-1). the results showed that apigenin 4'- o- alpha-rhamnopyranoside, apigenin 7- o- beta-glucopyranosyl-4'- o- alpha-rhamnopyranoside, tricin 7- o- beta-glucopyranoside, tricin, and isoscopoletin possessed inhibitory activity against hbv replication. protocatechuyl aldehyde exhibited an inhibiting activity on hsv-1 repli ...200516395649
the kaposi's sarcoma-associated herpesvirus g protein-coupled receptor as a therapeutic target for the treatment of kaposi's sarcoma.the kaposi's sarcoma-associated herpesvirus (kshv) encodes a g protein-coupled receptor (vgpcr) that has been implicated in the initiation of kaposi's sarcoma, identifying vgpcr as an attractive target for preventing kaposi's sarcoma. however, as only a fraction of cells in advanced kaposi's sarcoma lesions express vgpcr, it is unclear whether this unique viral oncogene contributes to kaposi's sarcoma progression. we therefore set out to determine whether the few cells that express vgpcr in esta ...200616397229
etiology of aseptic meningitis and encephalitis in an adult population.to investigate the etiology of aseptic meningitis and encephalitis in an adult population using modern microbiologic methods.200616401850
sexually transmitted infections, blood-borne viruses and risk behaviour in an australian senior high school population--the shlirp study.to determine the feasibility and acceptability of screening for sexually transmitted infections and blood-borne viruses and to study the profile of sexual activity and other risk behaviours in a senior high school population.200516402670
herpes simplex virus disrupts nf-kappab regulation by blocking its recruitment on the ikappabalpha promoter and directing the factor on viral genes.herpes simplex viruses (hsvs) are able to hijack the host-cell ikappab kinase (ikk)/nf-kappab pathway, which regulates critical cell functions from apoptosis to inflammatory responses; however, the molecular mechanisms involved and the outcome of the signaling dysregulation on the host-virus interaction are mostly unknown. here we show that in human keratinocytes hsv-1 attains a sophisticated control of the ikk/nf-kappab pathway, inducing two distinct temporally controlled waves of ikk activity ...200616407234
famciclovir for the treatment of recurrent genital and labial herpes lesions.famciclovir (famvir, novartis) is an effective treatment for herpes zoster and herpes simplex. two separate studies recently examined the effectiveness of single high doses of famciclovir for treating recurrent genital herpes and labial herpes (cold sores). in the randomized, placebo-controlled studies, patients initiated treatment at the first onset of symptoms. for the treatment of genital herpes, a 1,000 mg b.i.d. dose of famciclovir had significant advantages over the placebo, reducing the t ...200516408140
treatment of schwannomas with an oncolytic recombinant herpes simplex virus in murine models of neurofibromatosis type 2.gene therapy for schwannomas was evaluated in two mouse models of neurofibromatosis type 2 (nf2): (1) a transgenic model in which mice express a dominant mutant form of merlin and spontaneously develop schwannomas, and (2) a xenograft model in which human schwannoma tissue is implanted subcutaneously into immune- compromised mice. in both models, schwannoma volumes were monitored by magnetic resonance imaging (mri) and showed strong gadolinium enhancement typical of these tumors in humans. both ...200616409122
the inner tegument promotes herpes simplex virus capsid motility along microtubules in vitro.after viral fusion, capsids of the neurotropic herpes simplex virus are transported along microtubules (mt) to the nuclear pores for viral genome uncoating, nuclear transcription and replication. after assembly and egress from the nucleus, cytosolic capsids are transported to host membranes for secondary envelopment or to the axon terminal for further viral spread. using gfp-tagged capsids, cy3-labelled mt and cytosol, we have reconstituted viral capsid transport in vitro. in the presence of atp ...200616420530
herpes simplex virus type 1 in peptic ulcer disease: an inverse association with helicobacter pylori.to assess the frequency of herpes simplex virus type i in upper gastrointestinal tract ulcers and normal mucosa with the modern and better assays and also with a larger number of well characterized patients and controls and its relationship to helicobacter pylori(h pylori).200516425358
antiviral property and mechanisms of a sulphated polysaccharide from the brown alga sargassum patens against herpes simplex virus type 1.a sulphated polysaccharide (sp-2a) from the brown alga sargassum patens (kütz.) agardh (sargassaceae) was found to significantly inhibit the in vitro replication of both the acyclovir (acv)-sensitive and -resistant strains of herpes simplex virus type 1 (hsv-1), in dose-dependent manners, with 50% inhibitions occurring with 1.5-5.3 microg/ml of the polysaccharide. sp-2a exhibited extracellular virucidal activity only against the acv-sensitive strains, but not the resistant strain, at the concent ...200616427262
triple combination of oncolytic herpes simplex virus-1 vectors armed with interleukin-12, interleukin-18, or soluble b7-1 results in enhanced antitumor efficacy.conditionally replicating herpes simplex virus-1 (hsv-1) vectors are promising therapeutic agents for cancer. insertion of therapeutic transgenes into the viral genome should confer desired anticancer functions in addition to oncolytic activities. herein, using bacterial artificial chromosome and two recombinase-mediated recombinations, we simultaneously created four "armed" oncolytic hsv-1, designated vhsv-b7.1-ig, vhsv-interleukin (il)-12, vhsv-il-18, and vhsv-null, which express murine solubl ...200616428511
transgenic reporter mouse for bioluminescence imaging of herpes simplex virus 1 infection in living mice.bioluminescence imaging allows spatial and temporal progression of viral infection to be detected and quantified in living mice, thereby providing a new approach for studies of viral-host pathogenesis. it has been necessary to construct and validate recombinant reporter viruses that express firefly luciferase to investigate viral replication and spread with this imaging technology. this strategy greatly limits the ability to analyze multiple strains of virus and/or existing viral mutants, and re ...200616430938
synthesis and antiviral activity of some 2-substituted 3-formyl- and 3-cyano-5,6-dichloroindole nucleosides.a series of dichlorinated indole nucleosides has been synthesized and tested for activity against human cytomegalovirus (hcmv) and herpes simplex virus type-1 (hsv-1) and for cytotoxicity. the isopropylidene-protected analogs of the previously reported 3-formyl-2,5,6-trichloro-1-(beta-dribofuranosyl)indole (ftcri) and 3-cyano-2,5, 6-trichloro-1-(beta-d-ribofuranosyl)indole (ctcri) were modified by nucleophilic displacement of the 2-chloro substituent using secondary amines. deprotection of the i ...200516438038
2-substituted furans from the roots of polyalthia evecta.four new 2-substituted furans, 19-(2-furyl)nonadeca-5,7-diynoic acid (1), 19-(2-furyl)nonadeca-5-ynoic acid (2), 1-(2-furyl)pentacosa-7,9-diyne (3), and ester 21-(2-furyl)heneicosa-14,16-diyne-19-(2-furyl)nonadeca-5,7-diynoate (4) have been isolated from the roots of polyalthia evecta. their structures were established by spectroscopic techniques. compounds 1 and 1a showed antiplasmodial activity. the acids 1 and 2 exhibited antiviral activity against herpes simplex type 1. in addition, 5 also s ...200616441071
[autophagic host defense mechanism]. 200616457203
prenatal diagnosis of an exceptional intrauterine herpes simplex type 1 infection.to assess ultrasound findings of a fetus with intrauterine growth retardation (iugr) and skin damage, related to intrauterine herpes simplex virus (hsv) infection.200616463294
interactions between dna viruses, nd10 and the dna damage response.nd10 are small nuclear substructures that are defined by the presence the promyelocytic leukaemia protein pml. many other proteins have been detected within nd10, a complexity that is reflected in reports of their involvement in multiple cellular pathways that include the regulation of gene expression, chromatin dynamics, protein modification, apoptosis, p53 function, senescence, dna repair, the interferon response and viral infection. this review summarizes recent evidence of similarities betwe ...200616469050
structural characterization of the ul25 dna-packaging protein from herpes simplex virus type 1.herpesviruses replicate their double stranded dna genomes as high-molecular-weight concatemers which are subsequently cleaved into unit-length genomes by a complex mechanism that is tightly coupled to dna insertion into a preformed capsid structure, the procapsid. the herpes simplex virus type 1 ul25 protein is incorporated into the capsid during dna packaging, and previous studies of a null mutant have demonstrated that its function is essential at the late stages of the head-filling process, e ...200616474137
human herpesvirus 1 ul24 gene encodes a potential pd-(d/e)xk endonuclease.using meta-basic, a highly sensitive method for detection of distant similarity between proteins, we have identified another potential pd-(d/e)xk endonuclease in human herpesvirus 1 (hhv-1) encoded by the ul24 gene. the universal presence of ul24 in completed herpesviral genomes of three major subfamilies, alphaherpesvirinae, betaherpesvirinae, and gammaherpesvirinae, suggests a fundamental role for this predicted pd-(d/e)xk endonuclease activity in the viral life cycle.200616474163
glioma virotherapy: effects of innate immune suppression and increased viral replication capacity.oncolytic viruses are genetically altered replication-competent viruses that infect, and reproduce in, cancer cells but do not harm normal cells. on lysis of the infected cells, the newly formed viruses burst out and infect other tumor cells. experiments with injecting mutant herpes simplex virus 1 (hrr3) into glioma implanted in brains of rats show lack of efficacy in eradicating the cancer. this failure is attributed to interference by the immune system. initial pretreatment with immunosuppres ...200616489036
rna-binding of the human cytomegalovirus transactivator protein ul69, mediated by arginine-rich motifs, is not required for nuclear export of unspliced rna.the human cytomegalovirus protein pul69 belongs to a family of regulatory factors that is conserved within the herpesviridae and includes the proteins icp27 of herpes simplex virus type 1 and eb2 of epstein-barr virus. icp27 and eb2 have been shown to facilitate the nuclear export of viral mrnas via interacting with the cellular mrna export factor ref. furthermore, direct rna-binding of these proteins was found to be essential for their stimulating effects on mrna export. recently, we demonstrat ...200616500893
epitope mapping of herpes simplex virus type 2 gh/gl defines distinct antigenic sites, including some associated with biological function.the gh/gl complex plays an essential role in virus entry and cell-cell spread of herpes simplex virus (hsv). very few immunologic reagents were previously available to either identify important functional regions or gain information about structural features of this complex. therefore, we generated and characterized a panel of 31 monoclonal antibodies (mabs) against hsv type 2 (hsv-2) gh/gl. fourteen mabs bound to a conformation-dependent epitope of the gh2/gl2 complex, and all blocked virus spr ...200616501070
degradation of fibrillar collagen in a human melanoma xenograft improves the efficacy of an oncolytic herpes simplex virus vector.oncolytic viral therapy provides a promising approach to treat certain human malignancies. these vectors improve on replication-deficient vectors by increasing the viral load within tumors through preferential viral replication within tumor cells. however, the inability to efficiently propagate throughout the entire tumor and infect cells distant from the injection site has limited the capacity of oncolytic viruses to achieve consistent therapeutic responses. here we show that the spread of the ...200616510565
[herpes simplex virus type 1 and 2 (hsv-1,2) dna detection by pcr during genital herpes].the oligonucleotide primers for herpes simplex virus type 1 and 2 dna detection are developed. in examined group of patients with genital herpes the virus of type 2 and type 1 was detected in 63% and 26% cases, respectively. the mixed infection of both types is revealed in 11% of the patients.200616512611
4-1bb costimulation enhances hsv-1-specific cd8+ t cell responses by the induction of cd11c+cd8+ t cells.since 4-1bb plays a predominant role in cd8+ t cell responses, we investigated the effects of 4-1bb triggering on the primary and memory cd8+ t responses to hsv-1 infection. 4-1bb was detected on 10-15% of cd4+ and cd8+ t cells following the infection. 4-1bb-positive t cells were in the proliferative mode and showed the enhanced expression of anti-apoptotic proteins. agonistic anti-4-1bb treatment exerted preferential expansion of cd8+ t cells and gb/h-2kb-positive cd8+ t cells, and enhanced cyt ...200616524567
anatomical mapping of human herpesvirus reservoirs of infection.following primary infection, all eight human herpesviruses persist lifelong in the human host. however, a mapping of all anatomic sites of human herpesvirus persistence is lacking. fresh tissue specimens representing approximately 40 major anatomic sites from eight autopsies were screened using a recently developed real-time pcr method for detection of all eight human herpesviruses. patients with evidence of active herpesvirus infection (herpes simplex 1 (hsv-1), herpes simplex 2 (hsv-2), varice ...200616528368
characterization of the varicella zoster virus (vzv)-specific intra-ocular t-cell response in patients with vzv-induced uveitis.varicella zoster virus (vzv) is a well-known cause of infectious uveitis. the aim of this study was to characterize the vzv-specific t-cell response in eyes of patients with vzv-induced uveitis. t-cell lines (tcl) were generated by mitogenic stimulation of intra-ocular fluid (iof) samples obtained from eight patients with vzv-induced uveitis. two patients with herpes simplex virus (hsv)-induced uveitis were included as disease controls. characterization of individual t-cells in the tcl was perfo ...200616530754
varicella-zoster virus open reading frame 10 is a virulence determinant in skin cells but not in t cells in vivo.the open reading frame 10 (orf10) of varicella-zoster virus (vzv) encodes a tegument protein that enhances transactivation of vzv genes and has homology to herpes simplex virus type 1 (hsv-1) vp16. while vp16 is essential for hsv replication, orf10 is dispensable for vaccine oka (voka) growth in vitro. we used parent oka (poka) cosmids to delete orf10, producing poka delta10; point mutations that disrupted the acidic activation domain and the putative motif for binding human cellular factor 1 (h ...200616537591
icp0 is not required for efficient stress-induced reactivation of herpes simplex virus type 1 from cultured quiescently infected neuronal cells.viral genes sufficient and required for herpes simplex virus type 1 (hsv-1) reactivation were identified using neuronally differentiated pc12 cells (nd-pc12 cells) in which quiescent infections with wild-type and recombinant strains were established. in this model, the expression of icp0, vp16, and icp4 from adenovirus vectors was sufficient to reactivate strains 17+ and kos. the transactivators induced similar levels of reactivation with kos; however, 17+ responded more efficiently to icp0. to ...200616537603
yatein from chamaecyparis obtusa suppresses herpes simplex virus type 1 replication in hela cells by interruption the immediate-early gene expression.inhibitory effects of methanolic extracts from nine chinese herbs on herpes simplex virus type 1 (hsv-1) replication were studied. by a bioassay-guided fractionation procedure, yatein (c(22)h(23)o(7); m.w.399) was isolated from chamaecyparis obtusa; yatein significantly suppressed hsv-1 multiplication in hela cells without apparent cytotoxicity. to further localize the point in the hsv-1 replication cycle where arrest occurred, a set of key regulatory events leading to the viral multiplication w ...200616540181
neonatal herpes simplex virus infection presenting as acute liver failure: prevalent role of herpes simplex virus type i.acute liver failure (alf) in neonates is rare but carries a high mortality without liver transplantation. herpes simplex virus (hsv) is one of the microbes that more commonly causes alf and is potentially treatable; hence, early diagnosis and treatment are important to avoid progression to liver failure.200616540797
incidence and prevalence of herpes simplex virus infections in adolescent women.we conducted this study to examine the incidence, prevalence, and risk factors for herpes simplex virus (hsv) 1 and hsv 2 infection in a cohort of young women who were closely followed for acquisition of sexually transmitted infections.200616540882
type specific seroprevalence of hsv-1 and hsv-2 in four geographical regions of poland.to examine the type specific seroprevalence of herpes simplex virus (hsv) types 1 and 2 infections, stratified by age and gender, and associated risk factors for hsv-2 seropositivity in poland.200616581747
prevalence of infection with herpes simplex virus types 1 and 2 in australia: a nationwide population based survey.studies demonstrating previous herpes simplex virus (hsv) type 2 infection as a risk factor for hiv transmission, and the development of a hsv vaccine candidate, have emphasised the need for worldwide population based studies of hsv seroprevalence. the only nationwide seroprevalence studies have been conducted in the united states.200616581748
evaluation of herpes simplex detection in corneal scrapings by three molecular methods.herpes simplex virus (hsv)-1 keratitis (hsk) is a sight-threatening ocular infection with worldwide occurrence. a prompt laboratory diagnosis is often very useful. the purpose of this study was to evaluate molecular methods as rapid diagnostic tools compared with cell culture of hsk. corneal scrapings from patients with clinically suspected hsk were tested by direct immunofluorescence assay (ifa) for hsv-1 antigen and by polymerase chain reaction (pcr) for hsv-1 dna, and an attempt for viral iso ...200616586022
cationic liposomes as potential carriers for ocular administration of peptides with anti-herpetic activity.in the present study the preparation, characterization and activity of cationic liposomes containing the secretory form of herpes simplex virus type 1 (hsv-1) glycoprotein b (gb1s) or two related polylysine rich peptides, namely dtk1 and dtk2, were described. the immunotherapeutic potential of these hsv antigens containing liposomes was examined with a rabbit ocular model of hsv-1 infection. our study indicates that the liposomes (i) are able to encapsulate quantitatively gb1s and around 30% the ...200616600535
induction of cytokine expression by herpes simplex virus in human monocyte-derived macrophages and dendritic cells is dependent on virus replication and is counteracted by icp27 targeting nf-kappab and irf-3.macrophages and dendritic cells (dcs) play essential roles in host defence against microbial infections. in the present study, it is shown that human monocyte-derived macrophages and dcs express both type i and type iii interferons (ifns) [ifn-alpha, ifn-beta and interleukin 28 (il-28), il-29, respectively], tumour necrosis factor alpha and the chemokines ccl5 and cxcl10 after herpes simplex virus 1 (hsv-1) infection. the cytokine-inducing activity of hsv-1 was dependent on viability of the viru ...200616603509
mesenchymal stem cells are susceptible to human herpesviruses, but viral dna cannot be detected in the healthy seropositive individual.allogeneic stem cell transplantation is often complicated by reactivation of herpesviruses. mesenchymal stem cells (msc) are immunomodulatory and may be used to treat graft-versus-host disease. we investigated if herpesviruses infect and can be transmitted by msc, and if msc suppress immune responses to various infectious agents. mesenchymal stem cells from healthy seropositive donors were evaluated with polymerase chain reaction for the most common herpesviruses: cytomegalovirus (cmv), herpes s ...200616604097
[hsv genes and their function]. 200616615453
[molecular mechanisms for suppression of interferon system by hsv-1 infection]. 200616615462
[epidemiology of genital herpes]. 200616615470
[acute retinal necrosis due to herpesviridae infections]. 200616615476
[meningitis]. 200616615482
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