Publications

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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
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
isoform-specific effects of apoe on hsv immediate early gene expression and establishment of latency.alzheimer's disease (ad) is a common and devastating neurodegenerative disease in which most cases are of unknown, sporadic origin. in addition to age, the most prevalent known risk factor for developing ad is carriage of the epsilon4 allele of apolipoprotein e (apoe). carriage of the epsilon2 or epsilon3 allele of apoe confers protection or no change in risk for ad, respectively. latent herpes simplex virus type 1 (hsv-1) infection in the brain concurrent with apoe4 carriage exacerbates risk fo ...200817101197
topical treatment with nerve growth factor in an animal model of herpetic keratitis.in vitro and in vivo studies demonstrated the antiviral efficacy of nerve growth factor (ngf) and its cyto-protective effect in herpes simplex virus (hsv)-infected cells. the aims of this study were to evaluate the role of endogenous ngf in hsv corneal infection, and the effects of topical ngf treatment on herpetic keratitis.200817479276
glycoprotein i of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region.glycoprotein i (gi) of herpes simplex virus type 1 (hsv-1) contains a tandem repeat (tr) region including the amino acids serine and threonine, residues that can be utilized for o-glycosylation. the length of this tr region was determined for 82 clinical hsv-1 isolates and the results revealed a polymorphic distribution of two to six or eight repeated blocks with a majority harbouring between two and four repeats. assessment of the o-glycosylation capacity of an acceptor peptide (stpstttstpsttt) ...200717485527
activation of endogenous retrovirus reverse transcriptase in multiple sclerosis patient lymphocytes by inactivated hsv-1, hhv-6 and vzv.human endogenous retroviruses (hervs) and herpesviruses have been associated with the development of multiple sclerosis (ms). these virus groups interact with each other and have been shown to induce synergistic immune responses. here, we focus on the possible role of herpesviruses as contributing factors in herv activation. we demonstrate the ability of hsv-1, hhv-6, and vzv antigens to induce higher rt activity in peripheral lymphocytes from ms patients vs. controls during the first 6 days pos ...200717493688
hsv-1 amplicon-mediated post-transcriptional inhibition of rad51 sensitizes human glioma cells to ionizing radiation.standard treatment for glioblastoma multiforme and other brain tumors consists of surgical resection followed by combined radio-/chemotherapy. however, radiation resistance of tumor cells limits the success of this treatment, and the tumors invariably recur. therefore, the selective inhibition of molecular mediators of radiation resistance may provide therapeutic benefit to the patient. one of these targets is the rad51 protein, which is a key component of the homologous recombinational repair o ...200717495946
epitope mapping of hsv-1 glycoprotein k (gk) reveals a t cell epitope located within the signal domain of gk.glycoprotein k (gk) is a virion envelope component of herpes simplex virus types 1 (hsv-1) and 2 (hsv-2), which plays an important role in virion morphogenesis and egress. we previously demonstrated that immunization of mice with gk, but not with any of the 10 other hsv-1 glycoproteins, resulted in exacerbation of corneal scarring and herpetic dermatitis following ocular hsv-1 infection. however, little is known about the gk epitope(s) that is (are) involved in t cell activities in vitro or in v ...200717499382
antigen-presenting particle technology using inactivated surface-engineered viruses: induction of immune responses against infectious agents.developments in cell-based and gene-based therapies are emerging as highly promising areas to complement pharmaceuticals, but present day approaches are too cumbersome and thereby limit their clinical usefulness. these shortcomings result in procedures that are too complex and too costly for large-scale applications. to overcome these shortcomings, we described a protein delivery system that incorporates over-expressed proteins into viral particles that are non-infectious and stable at room temp ...200717504532
effects of g207, a conditionally replication-competent oncolytic herpes simplex virus, on the developing mammalian brain.viral oncolytic therapy for malignant brain tumors involves local intratumoral delivery of a genetically engineered virus with tumor cell-specific lytic activity. promising preliminary results have been achieved in preclinical models with g207, a replication-competent herpes simplex virus type 1 constructed with multiple directed mutations. although the safety of g207 has been demonstrated in adults, application of viral oncolytic therapy to children with brain tumors has been delayed because of ...200717505980
listeria monocytogenes encephalitis mimicking herpes simplex virus encephalitis: the differential diagnostic importance of cerebrospinal fluid lactic acid levels.listeria monocytogenes is a common cause of bacterial meningitis in elderly patients and in those with impaired cellular immunity. the most common central nervous system infection caused by l. monocytogenes is acute bacterial meningitis; meningoencephalitis is uncommon and encephalitis is rare. early diagnosis of l. monocytogenes meningitis is difficult because only 50% of cerebrospinal fluid (csf) gram stains are negative. l. monocytogenes is one of the few central nervous system pathogens asso ...200717509430
[comparative study of several methods for producing experimental animal model of viral facial palsy].to select the optimal method for developing experimental animal model of viral facial paralysis by comparing several inoculation methods.200717511177
acute retinal necrosis as a late sequela of herpes simplex type 1 encephalitis in a child.herpes simplex virus (hsv) is a common infection that occasionally presents with destructive lesions. two of the most feared presentations of hsv are encephalitis and acute retinal necrosis. although there are numerous reports of acute retinal necrosis presenting after hsv-2 infection in children, it has been rarely reported in children after hsv-1 infection. herein we report a child who developed acute retinal necrosis 17 months after hsv-1 encephalitis.200717512230
two-color fluorescence analysis of individual virions determines the distribution of the copy number of proteins in herpes simplex virus particles.we present a single virion method to determine absolute distributions of copy number in the protein composition of viruses and apply it to herpes simplex virus type 1. using two-color coincidence fluorescence spectroscopy, we determine the virion-to-virion variability in copy numbers of fluorescently labeled tegument and envelope proteins relative to a capsid protein by analyzing fluorescence intensity ratios for ensembles of individual dual-labeled virions and fitting the resulting histogram of ...200717513380
virus inactivation by protein denaturants used in affinity chromatography.virus inactivation by a number of protein denaturants commonly used in gel affinity chromatography for protein elution and gel recycling has been investigated. the enveloped viruses sindbis, herpes simplex-1 and vaccinia, and the non-enveloped virus polio-1 were effectively inactivated by 0.5 m sodium hydroxide, 6 m guanidinium thiocyanate, 8 m urea and 70% ethanol. however, ph 2.6, 3 m sodium thiocyanate, 6 m guanidinium chloride and 20% ethanol, while effectively inactivating the enveloped vir ...200717517521
a herpes simplex virus gd-yfp fusion glycoprotein is transported separately from viral capsids in neuronal axons.two models describing how alphaherpesviruses exit neurons differ with respect to whether nucleocapsids and envelope glycoproteins travel toward axon termini separately or as assembled enveloped virions. recently, a pseudorabies virus glycoprotein d (gd)-green fluorescent protein fusion was found to colocalize with viral capsids, supporting anterograde transport of enveloped virions. previous antibody staining experiments demonstrated that herpes simplex virus (hsv) glycoproteins and capsids are ...200717522199
synthesis of neutral and cationic tripyridylporphyrin-d-galactose conjugates and the photoinactivation of hsv-1.neutral and cationic tripyridylporphyrin-d-galactose conjugates were synthesized and their antiviral activity against herpes simplex virus type 1 (hsv-1) was evaluated. at non-cytotoxic concentrations the studied compounds show significant antiviral activity after photoactivation. the influence of photoactivation on drug treated cells was also analyzed, at different times of infection with hsv-1, for a neutral (1b) and a cationic glycoporphyrin (3b) derivative. the results show that the inhibiti ...200717524654
adenoviral gene transfer in bovine adrenomedullary and murine pheochromocytoma cells: potential clinical and therapeutic relevance.recombinant adenoviruses (rad) have been widely used as gene transfer vectors both in the laboratory and in human clinical trials. in the present study, we investigated the effects of adenoviral-mediated gene transfer in primary bovine adrenal chromaffin cells (bacc) and a murine pheochromocytoma cell line (mpc). cells were infected with one of three nonreplicating e1/e3-deleted (e1(-)/e3(-)) rad vectors: ad.gfp, expressing a green fluorescent protein (gfp); ad.null, expressing no transgene; or ...200717525127
ménétrier's disease associated with herpes infection: response to treatment with acyclovir. 200717531647
herpes simplex virus type-1 meningoencephalitis showing disseminated cortical lesions.we report a 41-year-old man with meningoencephalitis associated with herpes simplex virus type 1 (hsv-1). the patient developed fever, headache and dysuria followed by generalized convulsion and neck stiffness, and the csf showed pleocytosis. the titers of enzyme-linked immunosorbent assay against hsv measured 6 days after onset showed a significant rise; igg antibody 4.89 (<0.2) and igm antibody 1.45 (<0.8) in csf, igg antibody 46.1 (<2.0) and igm antibody 1.76 (<0.8) in the serum. the antibody ...200717541231
herpes simplex virus glycoproteins gb and gh function in fusion between the virion envelope and the outer nuclear membrane.herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm and, ultimately, to exit cells. it is believed that herpesvirus nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane (nm). to reach the cytoplasm these enveloped particles must fuse with the outer nm and the unenveloped capsids then acquire a second envelope in the trans-golgi network. little is known about the process by which herpesviruses virions fuse with the outer nm. here we ...200717548810
a mutation in the human herpes simplex virus type 1 ul52 zinc finger motif results in defective primase activity but can recruit viral polymerase and support viral replication efficiently.herpes simplex virus type 1 (hsv-1) encodes a heterotrimeric helicase/primase complex consisting of ul5, ul8, and ul52. ul5 contains conserved helicase motifs, while ul52 contains conserved primase motifs, including a zinc finger motif. although hsv-1 and hsv-2 ul52s contain a leucine residue at position 986, most other herpesvirus primase homologues contain a phenylalanine at this position. we constructed an hsv-1 ul52 l986f mutation and found that it can complement a ul52 null virus more effic ...200717553899
susceptibility of cancer cells to herpes simplex virus-dependent apoptosis.apoptosis has recently been associated with herpes simplex virus 1 (hsv-1) latency and disease severity. there is an intricate balance between pro- and anti-apoptotic processes during hsv-1 infection. when anti-apoptotic pathways are suppressed, this balance is upset and the cells die by apoptosis, referred to here as hsv-1-dependent apoptosis (hdap). it has been observed previously that hela cancer cells exhibit an enhanced sensitivity to hdap. here, a series of specific patient-derived cancer ...200717554017
treatment of inflamed pancreas with enkephalin encoding hsv-1 recombinant vector reduces inflammatory damage and behavioral sequelae.this study assessed the efficacy of pancreatic surface delivered enkephalin (enk)-encoding herpes simplex virus type 1 (hsv-1) on spontaneous behaviors and spinal cord and pancreatic enkephalin expression in an experimental pancreatitis model. replication-defective hsv-1 with proenkephalin complementary dna (cdna) (hsv-enk) or control beta-galactosidase cdna (hsv-beta-gal), or media vehicle (veh) was applied to the pancreatic surface of rats with dibutyltin dichloride (dbtc)-induced pancreatitis ...200717565349
neuroimaging of herpesvirus infections in children.six members of the herpesvirus family cause well-described neurologic disease in children: herpes simplex virus-1 (hsv-1), herpes simplex virus-2 (hsv-2), varicella-zoster (vzv), epstein-barr (ebv), cytomegalovirus (cmv), and human herpes virus-6 (hhv-6). when herpesviruses infect the central nervous system (cns), the clinical presentation is non-specific and often confounding. the clinical urgency is often underscored by progressive neurologic deficits, seizures, or even death, and prompt diagn ...200717572889
enzymatic therapeutic index of acyclovir. viral versus human polymerase gamma specificity.we have examined the kinetics of incorporation of acyclovir triphosphate by the herpes simplex virus-1 dna polymerase holoenzyme (pol-ul42) and the human mitochondrial dna polymerase using transient kinetic methods. for each enzyme, we compared the kinetic parameters for acyclovir to those governing incorporation of dgtp. the favorable ground state dissociation constant (6 microm) and rate of polymerization (10 s(-1)) afford efficient incorporation of acyclovir triphosphate by the pol-ul42 enzym ...200717573351
asymptomatic shedding of hsv-1 in patients undergoing oral surgical procedures and attending for noninvasive treatment.oral surgery and stress can trigger and/or increase asymptomatic shedding of herpes simplex virus type-1 (hsv-1) into human saliva. in this investigation we examined the frequency of hsv-1 shedding in 32 patients undergoing an oral surgery procedure compared with 40 control patients attending for noninvasive treatment. control patients comprised 18 migraine patients and 22 patients with temporomandibular (tmd) joint problems. nested-pcr was carried out on oral rinses collected from each patient ...200717577329
psychological stress compromises cd8+ t cell control of latent herpes simplex virus type 1 infections.recurrent hsv-1 ocular disease results from reactivation of latent virus in trigeminal ganglia, often following immunosuppression or exposure to a variety of psychological or physical stressors. hsv-specific cd8+ t cells can block hsv-1 reactivation from latency in ex vivo trigeminal ganglia cultures through production of ifn-gamma. in this study, we establish that either cd8+ t cell depletion or exposure to restraint stress permit hsv-1 to transiently escape from latency in vivo. restraint stre ...200717579052
effects of bicistronic lentiviral vector-mediated herpes simplex virus thymidine kinase/ganciclovir system on human lens epithelial cells.posterior capsule opacification (pco) is the most common complication after phacoemulsification cataract surgery. hyperplasia of the lens epithelial cell after phacoemulsification is thought to be an important feature contributing to pco. in this study,we investigated the feasibility of killing the human lens epithelial cells (hlecs) by lentivirus-mediated herpes simplex virus thymidine kinase (hsv-tk) gene/ganciclovir (gcv) in hlecs and studied the bystander effect. hlecs were infected with len ...200717364733
the human cytomegalovirus mhc class i homolog ul18 inhibits lir-1+ but activates lir-1- nk cells.the inhibitory leukocyte ig-like receptor 1 (lir-1, also known as ilt2, cd85j, or lilrb1) was identified by its high affinity for the human cmv (hcmv) mhc class i homolog gpul18. the role of this lir-1-gpul18 interaction in modulating nk recognition during hcmv infection has previously not been clearly defined. in this study, lir-1(+) nkl cell-mediated cytotoxicity was shown to be inhibited by transduction of targets with a replication-deficient adenovirus vector encoding ul18 (rad-ul18). fibrob ...200717372005
presence of herpes simplex virus on the oral mucosa in patients undergoing chemotherapy.the aim of this study was to confirm the presence of herpes simplex virus type 1 and 2 on the oral mucosa, in patients undergoing chemotherapy, by means of polymerase chain reaction (pcr).200717373422
role of tumor invasiveness, the extracellular matrix, and chromatin sequestration in the susceptibility of uveal melanoma to herpes simplex virus type 1.to better understand determinants of susceptibility/resistance of uveal melanomas to herpes simplex virus type 1 (hsv-1) oncolytic therapy, uveal melanoma cell lines of low (ocm1a) and of high (m619, mum2b) invasive potential were infected with hsv-1 either in the presence or absence of a laminin-rich extracellular matrix (matrigel). ocm1a cultures were destroyed faster by hsv-1 than m619 and mum2b cultures. in the presence of matrigel, all melanoma cultures demonstrated delayed destruction by h ...200717386925
molecular pet imaging of hsv1-tk reporter gene expression using [18f]feau.non-invasive imaging of transgene expression requires the appropriate combination of a reporter gene and a reporter probe. [18f]feau positron emission tomography (pet) is used for the assessment of herpes simplex virus type-1 thymidine kinase gene expression. hybrid aav phage (termed aavp) can be adapted to transduce mammalian cells by targeting to a specific receptor. we evaluated a targeted aavp vector using [18f]feau pet. this protocol describes [18f]feau production and dosing, micro-pet imag ...200717406603
a role for plasmacytoid dendritic cells in the rapid il-18-dependent activation of nk cells following hsv-1 infection.natural killer (nk) cells play a crucial role in the initial response to viral infections but the mechanisms controlling their activation are unclear. we show a rapid and transient activation of nk cells that results in the production of ifn-gamma immediately following infection with herpes simplex virus type 1 (hsv-1). activation of nk cells leading to synthesis of ifn-gamma was not mediated by a direct interaction with virus but required the presence of additional cell types and was largely de ...200717407097
antiapoptotic activity of bovine herpesvirus type-1 (bhv-1) ul14 protein.viruses have evolved different strategies to interfere with apoptotic pathways in order to halt cellular responses to infection. one previous study showed that transient transfection of bovine herpesvirus type-1 (bhv-1) ul14 protein is efficient in protecting madin darby kidney (mdbk) and human chronic myelogenous leukemia (k562) cells from sorbitol-induced apoptosis. this protein corresponds to a putative protein of bhv-1, which shares aminoacid sequence with a part of the peptide-binding domai ...200717408888
in vivo fitness and virulence of a drug-resistant herpes simplex virus 1 mutant.two important issues regarding a virus mutant that is resistant to an antiviral drug are its ability to replicate in animal hosts (in vivo fitness) relative to other genetic variants, including wild type, and its ability to cause disease. these issues have been investigated for a herpes simplex virus 1 mutant that is resistant to thiourea compounds, which inhibit encapsidation of viral dna. following corneal inoculation of mice, the mutant virus replicated very similarly to its wild-type parent ...200717412967
perineal herpes simplex infection in bedridden geriatric patients.herpes simplex virus (hsv) lesions are prone to reactivation and recurrence in response to various local or systemic triggering factors.200717428112
us3 of herpes simplex virus type 1 encodes a promiscuous protein kinase that phosphorylates and alters localization of lamin a/c in infected cells.the herpes simplex virus type 1 (hsv-1) us3 gene encodes a serine/threonine kinase that, when inactivated, causes capsids to aggregate aberrantly between the inner and outer nuclear membranes (inm and onm, respectively) within evaginations/extensions of the perinuclear space. in both hep2 cells and an engineered cell line derived from hep2 cells expressing lamin a/c fused to enhanced green fluorescent protein (egfp-lamin a/c), lamin a/c localized mostly in a reticular pattern with small regions ...200717428859
a novel double-stable t-rex/gb cell line expressing glycoprotein b of herpes simplex virus 1.we established and characterized a new stable t-rex/gb cell line expressing gb of hsv-1 under tetracycline (tet) control. the expression of complete gb (120 k) in t-rex/gb cells was detected by western blot analysis with anti-hsv-1/ang/gb monoclonal antibody as early as 2 days after tet induction. inducibility and tightness of tet-regulated gb expression in t-rex/gb cell line was shown to be preserved after long-term culture (2 months) and after numerous freezing/thawing cycles as well. in this ...200717432944
sculpting the bicyclo[3.1.0]hexane template of carbocyclic nucleosides to improve recognition by herpes thymidine kinase.the replacement of the furanose ring by a cyclopentane in nucleosides generates a group of analogues known generically as carbocyclic nucleosides. these compounds have increased chemical and enzymatic stability due to the absence of a true glycosyl bond that characterizes conventional nucleosides. the additional fusion of a cyclopropane ring to the cyclopentane produces a bicyclo[3.1.0]hexane system that depending on its location relative to the nucleobase is able to lock the embedded cyclopenta ...200717451242
aquaporin 4 regulation during acute and long-term experimental herpes simplex virus encephalitis.structural damage of the central nervous system (cns) often leads to severely disabling residual symptoms despite effective antiviral therapy during herpes simplex virus encephalitis (hsve). edematous space-occupying lesions are pathological and neuroradiological well-known phenomena for this disease. the molecular mechanisms of brain edema development in hsve are poorly understood, the regulation of water brain-blood barrier (bbb) permeability might be disturbed. aquaporin 4 (aqp4) is the predo ...200717454447
performance of focus elisa tests for hsv-1 and hsv-2 antibodies among university students with no history of genital herpes.to define the performance characteristics of the focus elisa hsv-1 and hsv-2 assay among 100 university students.200717457239
diverse herpes simplex virus type 1 thymidine kinase mutants in individual human neurons and ganglia.mutations in the thymidine kinase gene (tk) of herpes simplex virus type 1 (hsv-1) explain most cases of virus resistance to acyclovir (acv) treatment. mucocutaneous lesions of patients with acv resistance contain mixed populations of tk mutant and wild-type virus. however, it is unknown whether human ganglia also contain mixed populations since the replication of hsv tk mutants in animal neurons is impaired. here we report the detection of mutated hsv tk sequences in human ganglia. trigeminal a ...200717459924
role of anti-glycoproteins d (anti-gd) and k (anti-gk) iggs in pathology of herpes stromal keratitis in humans.to assess the relative impact of antibodies specific for hsv-1 glycoproteins on eye disease in response to hsv-1 infection, the composition of antibodies specific for 10 of the viral glycoproteins, and the effect of anti-glycoprotein (g)d and anti-gk antibodies on antibody-dependent enhancement (ade).200717460278
dual infection with polyomavirus bk and acyclovir-resistant herpes simplex virus successfully treated with cidofovir in a bone marrow transplant recipient.a hematopoietic stem cell transplant recipient developed a mucosal herpes simplex virus-1 (hsv-1) infection while under acyclovir (acv) treatment (hsv was later shown to be resistant to acv). concomitantly, the patient presented a hemorrhagic cystitis (hc) due to polyomavirus bk, for which intravenous cidofovir (cdv) was prescribed. the patient benefited from the broad-spectrum anti-dna virus activity of cdv, and not only the hc resolved without signs of nephrotoxicity but also the hsv-1 lesions ...200717461998
isolation, identification and function of a novel anti-hsv-1 protein from grifola frondosa.a novel antiviral protein was purified from an extract of grifola frondosa fruiting bodies using a procedure that included 40% ammonium sulfate precipitation and deae-cellulose ion exchange chromatography, and designated gfahp. this protein inhibited herpes simplex virus type 1 (hsv-1) replication in vitro with an ic(50) value of 4.1 microg/ml and a therapeutic index >29.3. higher concentrations of gfahp (125 and 500 microg/ml) also significantly reduced the severity of hsv-1 induced blepharitis ...200717475344
the herpes simplex virus type 1 bgkl variant, unlike the bgol variant, shows a higher association with orolabial infection than with infections at other sites, supporting the variant-dispersion-replacement hypothesis.the identification and geographic distribution of the herpes simplex virus type 1 (hsv-1) bglii restriction fragment length polymorphism (rflp) variants named bgk(l) and bgo(l) in clinical isolates from orolabial and cutaneous sites were described in our previous reports, in which the dispersion and replacement of hsv-1 variants were proposed. the base substitution sites deduced from the bgk(l) multiple rflp variations were mapped to the u(l)12 (dnase), r(l)2 (alpha0 transactivator), and latency ...200717475752
quantitative analysis of herpes simplex virus type 1-specific memory b cells generated by different routes of infection.we compared the herpes simplex virus type 1 (hsv)-specific memory b cell (mbc) populations generated by footpad and intranasal infection in mice. both routes of infection generated transient antibody-secreting cell responses in the draining lymph nodes and spleen, and sustained circulating igg. hsv-specific igg mbcs, analyzed by limiting dilution assay approximately 8 weeks after infection, were distributed in a range of lymph nodes and in the spleen and peyer's patches. overall, the route of in ...200717113122
activators of potassium m currents have anticonvulsant actions in two rat models of encephalitis.opioid systems in hippocampus regulate excitability and kappa opioids have a role in anticonvulsant protection, but their mechanisms of action are incompletely understood. we examined the ability of opioid and nonopioid agents with overlapping ionic mechanisms and actions similar to kappa opioid agonists, to block seizures in rat models of encephalitis due to borna disease virus and herpes simplex virus type-1. naltrindole, a delta antagonist and thus a kappa opioid sparing agent, (10 mg/kg s.c. ...200717126318
dna vaccine-encoded glycoprotein b of hsv-1 fails to protect chronic morphine-treated mice against hsv-1 challenge.the use of morphine has been demonstrated to increase susceptibility to infections. herpes simplex virus type 1 (hsv-1) is a highly successful pathogen among immunocompromised individuals. in the present study, due to the importance of hsv vaccination in morphine abusers, the effects of chronic morphine exposure on the host response to a hsv-1 gb dna-based vaccine have been investigated. the study is addressing an important aspect of vaccine development among the susceptible (immunocompromised) ...200717126902
electron cryotomography reveals the portal in the herpesvirus capsid.herpes simplex virus type 1 is a human pathogen responsible for a range of illnesses from cold sores to encephalitis. the icosahedral capsid has a portal at one fivefold vertex which, by analogy to portal-containing phages, is believed to mediate genome entry and exit. we used electron cryotomography to determine the structure of capsids lacking pentons. the portal vertex appears different from pentons, being located partially inside the capsid shell, a position equivalent to that of bacteriopha ...200717151101
characterization of soluble glycoprotein d-mediated herpes simplex virus type 1 infection.herpes simplex virus type 1 (hsv-1) entry into permissive cells involves attachment to cell-surface glycosaminoglycans (gags) and fusion of the virus envelope with the cell membrane triggered by the binding of glycoprotein d (gd) to cognate receptors. in this study, we characterized the observation that soluble forms of the gd ectodomain (sgd) can mediate entry of gd-deficient hsv-1. we examined the efficiency and receptor specificity of this activity and used sequential incubation protocols to ...200717157347
synthesis of the 5-phosphono-pent-2-en-1-yl nucleosides: a new class of antiviral acyclic nucleoside phosphonates.a new class of acyclic nucleoside phosphonates, the 5-phosphono-pent-2-en-1-yl nucleosides and their hexadecyloxypropyl esters, were synthesized from butyn-1-ol. only the hexadecyloxypropyl esters showed antiviral activity against herpes simplex virus type 1, in vitro. hexadecyloxypropyl 1-(5-phosphono-pent-2-en-1-yl)-thymine was the most active and selective compound among the synthesized nucleotides with an ec50 value of 0.90 microm.200717166725
isolation of an enhancer from the rat tyrosine hydroxylase promoter that supports long-term, neuronal-specific expression from a neurofilament promoter, in a helper virus-free hsv-1 vector system.direct gene transfer into neurons, using a virus vector, has been used to study neuronal physiology and learning, and has potential for supporting gene therapy treatments for specific neurological diseases. many of these applications require high-level, long-term recombinant gene expression, in forebrain neurons. we previously showed that addition of upstream sequences from the rat tyrosine hydroxylase (th) promoter to a neurofilament heavy gene (nf-h) promoter supports long-term expression in f ...200717169349
antiviral activity obtained from aqueous extracts of the chilean soapbark tree (quillaja saponaria molina).natural, aqueous extracts of quillaja saponaria, the chilean soapbark tree, contain several physiologically active triterpenoid saponins that display strong adjuvant activity when used in either human or animal vaccines. in this paper, we describe studies that demonstrate a novel antiviral activity of quillaja extracts against six viruses: vaccinia virus, herpes simplex virus type 1, varicella zoster virus, human immunodeficiency viruses 1 and 2 (hiv-1, hiv-2) and reovirus. we demonstrate that m ...200717170461
acute retinal necrosis features, management, and outcomes.to determine the viral diagnosis and factors affecting the visual outcome of eyes with acute retinal necrosis.200717184841
visualization of the herpes simplex virus portal in situ by cryo-electron tomography.herpes simplex virus type 1 (hsv-1), the prototypical herpesvirus, has an icosahedral nucleocapsid surrounded by a proteinaceous tegument and a lipoprotein envelope. as in tailed bacteriophages, the icosahedral symmetry of the capsid is broken at one of the 12 vertices, which is occupied by a dodecameric ring of portal protein, ul6, instead of a pentamer of the capsid protein, ul19. the portal ring serves as a conduit for dna entering and exiting the capsid. from a cryo-em reconstruction of caps ...200717188319
synthesis and antiviral activity of c-fluoro-branched cyclopropyl nucleosides.a series of novel fluorocyclopropyl nucleosides were synthesized starting from acetol using the simmons-smith reaction as a key reaction. all the nucleosides synthesized were assayed against several viruses. among the compounds synthesized, the uracil analogue 22 showed moderate anti-hcmv activity (10.61 microg/ml, in ad-169).200717188402
the infected cell protein 0 encoded by bovine herpesvirus 1 (bicp0) induces degradation of interferon response factor 3 and, consequently, inhibits beta interferon promoter activity.the icp0 protein (bicp0) encoded by bovine herpesvirus 1 is the major viral regulatory protein because it stimulates all viral promoters and, consequently, productive infection. like other icp0 analogues encoded by alphaherpesvirinae subfamily members, bicp0 contains a zinc ring finger near its amino terminus that is necessary for activating transcription, regulating subcellular localization, and inhibiting interferon-dependent transcription. in this study, we discovered that sequences near the ...200717215277
short-course therapy for recurrent genital herpes and herpes labialis. 200717217895
sialic acid on herpes simplex virus type 1 envelope glycoproteins is required for efficient infection of cells.herpes simplex virus type 1 (hsv-1) envelope proteins are posttranslationally modified by the addition of sialic acids to the termini of the glycan side chains. although gc, gd, and gh are sialylated, it is not known whether sialic acids on these envelope proteins are functionally important. digestion of sucrose gradient purified virions for 4 h with neuraminidases that remove both alpha2,3 and alpha2,6 linked sialic acids reduced titers by 1,000-fold. digestion with a alpha2,3-specific neuramin ...200717229687
maintenance of endoplasmic reticulum (er) homeostasis in herpes simplex virus type 1-infected cells through the association of a viral glycoprotein with perk, a cellular er stress sensor.in the efforts of viruses to dominate and control critical cellular pathways, viruses generate considerable intracellular stress within their hosts. in particular, the capacity of resident endoplasmic reticulum (er) chaperones to properly process the acute increase in client protein load is significantly challenged. such alterations typically induce the unfolded protein response, one component of which acts through ire1 to restore er homeostasis by expanding the folding capabilities, whereas the ...200717229688
infectious delivery and expression of a 135 kb human frda genomic dna locus complements friedreich's ataxia deficiency in human cells.friedreich's ataxia (fa) is the most common recessive ataxia, affecting 1-2 in 50,000 caucasians, and there is currently no effective cure or treatment. fa results from a deficiency of the mitochondrial protein frataxin brought about by a repeat expansion in intron 1 of the frda gene. the main areas affected are the central nervous system (particularly the spinocerebellar system) and cardiac tissue. therapies aimed at alleviating the neurological degeneration have proved unsuccessful to date. he ...200717235301
seroprevalence of herpes simplex virus types 1 and 2 in pregnant women in the united states.the purpose of this study was to determine seroprevalence of herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) in a national cross-sectional sample of pregnant women.200717240228
blocks to herpes simplex virus type 1 replication in a cell line, tsbn2, encoding a temperature-sensitive rcc1 protein.circularization of the herpes simplex virus type 1 (hsv-1) genome is thought to be an important early event during the lytic cycle. previous studies from another laboratory using a cell line, tsbn2, that carries a temperature-sensitive mutation in the gene encoding the regulator of chromatin condensation 1 (rcc1) indicated that functional rcc1 was required for hsv-1 genome circularization and subsequent viral dna synthesis. here, hsv-1 infection of tsbn2 cells has been re-examined by utilizing b ...200717251553
concurrent cmv and ebv dnaemia is significantly correlated with a delay in the response to haart in treatment-naive hiv type 1-positive patients.the purpose of this study was to assess the qualitative single and multiple herpes virus dnaemia in the peripheral blood leukocytes (pbls) of hiv-1-positive patients and its impact on the response to highly active antiretroviral therapy (haart) and immune reconstitution. all (163) hiv-1-positive patients attending "syngros aids referral center" from november 2000 to february 2001 were recruited. cmv, hsv-1, hsv-2, ebv, and hhv-8 dna were detected in pbls by polymerase chain reaction (pcr). patie ...200717263627
acute retinal necrosis.acute retinal necrosis (arn) is a rare disease that is usually caused by one of the three neurotropic human herpesviruses - herpes simplex virus type 1(hsv-1), hsv-2 and varicella-zoster virus (vzv). although much is known about the clinical course of the disease and its treatment and about the viruses that cause it, comparatively little is known about its pathogenesis. this article will review the history of arn, the typical clinical findings, and methods of diagnosis. information from studies ...200717264500
nonimmune hydrops fetalis due to herpes simplex virus type 1. 200717266163
induction of strong antitumor immunity by an hsv-2-based oncolytic virus in a murine mammary tumor model.oncolytic viruses have shown considerable promise for the treatment of solid tumors. in previous studies, we demonstrated that a novel oncolytic virus (fuson-h2), constructed by replacing the serine/threonine protein kinase (pk) domain of the icp10 gene of type 2 herpes simplex virus (hsv-2) with the gene encoding the green fluorescent protein, can selectively replicate in and thus lyse tumor cells. 4t1 tumor cells are weakly immunogenic and the mammary tumors derived from them aggressively meta ...200717266169
ctcf-dependent chromatin boundary element between the latency-associated transcript and icp0 promoters in the herpes simplex virus type 1 genome.cells latently infected with herpes simplex virus (hsv) contain nucleosomal dna similar to that of host cell chromatin. recent studies have demonstrated that histones in the latency-associated transcript (lat) promoter and intron regions contain histone modifications permissive for transcription. however, those histones associated with the lytic-specific icp0 gene, which lies only 5 kb away, contain modifications typical of silenced chromatin. how this active chromatin is kept separate from the ...200717267480
epithelial herpetic simplex keratitis recurrence and graft survival after corneal transplantation in patients with and without atopy.to compare the incidence of herpes simplex virus (hsv) epithelial recurrence and graft survival after penetrating keratoplasty (pk) in patients with and without self-reported atopy.200717276382
delayed but not early glucocorticoid treatment protects the host during experimental herpes simplex virus encephalitis in mice.glucocorticoids (gcs) have not been established as an evidence-based therapy for herpes simplex virus (hsv) encephalitis. we sought to evaluate the effects of early versus delayed gc administration in a model of hsv-1 encephalitis.200717299711
quantitative demonstration of intrathecal synthesis of high affinity immunoglobulin g in herpes simplex encephalitis using affinity-mediated immunoblotting.three paired serial samples of csf and serum (from days 8, 13 and 22) were taken from a patient referred to the national hospital for neurology and neurosurgery with what was duly confirmed as having herpes simplex encephalitis using pcr. the samples were investigated using affinity-mediated immunoblotting followed by incubation with sodium thiocyanate. digitisation of the blots enabled further analysis. we showed that the clones of antigen-specific igg, which were produced intrathecally, were o ...200717303253
clinical experiment of mutant herpes simplex virus hf10 therapy for cancer.we reviewed our clinical trial using mutant herpes simplex virus "hf10". we have evaluated the safety and effect of hf10 against recurrent breast cancer since 2003 and also applied hf10 to non-resectable pancreatic cancer since 2005. an oncolytic herpes simplex virus type 1, mutant hf10, has been isolated and evaluated for anti-tumor efficacy in syngeneic immunocompetent mouse models. from long time before clinical trial, we have found that the mutant virus can have remarkable potential to effec ...200717346108
modulation of microglia and cd8(+) t cell activation during the development of stress-induced herpes simplex virus type-1 encephalitis.the central nervous system (cns) has been shown to be vulnerable to a variety of insults in animals exposed to glucocorticoids. for example, psychological stress, a known inducer of glucocorticoid production, enhances the susceptibility of mice to herpes simplex virus type-1 (hsv-1) infection and results in the development of hsv-1 encephalitis (hse). to determine the immune mechanisms by which stress promotes the development of hse, we examined the role of the glucocorticoid receptor (gr) and t ...200717349776
antiviral triterpenoids from the medicinal plant schefflera heptaphylla.schefflera heptaphylla (l.) frodin is a principal ingredient of an herbal tea formulation widely used for the treatment of common cold in southern china. an extract of the long leafstalk of the compound leaf of s. heptaphylla exhibited the most potent antiviral activity against respiratory syncytial virus (rsv). further antiviral-guided fractionation and isolation of the leafstalk extract of s. heptaphylla led to obtain two highly active pure triterpenoids, namely 3alpha-hydroxylup-20(29)-ene-23 ...200717357972
selective retention of herpes simplex virus-specific t cells in latently infected human trigeminal ganglia.primary infection with herpes simplex virus 1 (hsv-1) and varicella zoster virus (vzv) results in lifelong latent infections of neurons in sensory ganglia such as the trigeminal ganglia (tg). it has been postulated that t cells retained in tg inhibit reactivation of latent virus. the acquisition of tg specimens of individuals within hours after death offered the unique opportunity to characterize the phenotype and specificity of tg-resident t cells in humans. high numbers of activated cd8(+) t c ...200717360672
hsv-1-mediated il-1 receptor antagonist gene therapy ameliorates mog(35-55)-induced experimental autoimmune encephalomyelitis in c57bl/6 mice.primary proinflammatory cytokines, such as il-1beta, play a crucial pathogenic role in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (eae), and may represent, therefore, a suitable therapeutic target. we have previously established the delivery of anti-inflammatory cytokine genes within the central nervous system (cns), based on intracisternal (i.c.) injection of non-replicative hsv-1-derived vectors. here we show the therapeutic efficacy of i.c. administratio ...200716929354
a conserved region of the herpes simplex virus type 1 tegument protein vp22 facilitates interaction with the cytoplasmic tail of glycoprotein e (ge).herpes simplex virus type 1 (hsv-1) virions, contain a proteinaceous layer termed the tegument that lies between the nucleocapsid and viral envelope. current evidence suggests that viral glycoprotein tails play a role in the recruitment of tegument-coated capsids to the site of final envelopment; vesicles derived from the trans-golgi network. we have identified an interaction between vp22, an abundant tegument protein and the cytoplasmic tail of glycoprotein e (ge). this interaction was identifi ...200716997344
cytoplasmic residues of herpes simplex virus glycoprotein ge required for secondary envelopment and binding of tegument proteins vp22 and ul11 to ge and gd.the final assembly of herpes simplex virus (hsv) involves binding of tegument-coated capsids to viral glycoprotein-enriched regions of the trans-golgi network (tgn) as enveloped virions bud into tgn membranes. we previously demonstrated that hsv glycoproteins ge/gi and gd, acting in a redundant fashion, are essential for this secondary envelopment. to define regions of the cytoplasmic (ct) domain of ge required for secondary envelopment, hsvs lacking gd and expressing truncated ge molecules were ...200717035313
use of herpes simplex virus type 1-based amplicon vector for delivery of small interfering rna.silencing of gene expression by small interfering rnas (sirnas) is rapidly becoming a powerful tool for genetic analysis of mammalian cells. the use of dna-based plasmid vectors to achieve transient and stable expression of sirna has been developed to avoid the problems of double-stranded oligonucleotides transfection. these vectors direct the transcription of small hairpin rnas (shrnas) from a polymerase-iii (h1 or u6)-rna gene promoter. however, numerous disadvantages remain, including low tra ...200717051250
tolerance of loop-mediated isothermal amplification to a culture medium and biological substances.to simplify the molecular detection of micro-organisms, we evaluated the tolerance of loop-mediated isothermal amplification (lamp) to a culture medium and some biological substances. the sensitivity of lamp was less affected by the various components of the clinical samples than was polymerase chain reaction (pcr); therefore, dna purification from samples could be omitted.200717011631
apoptosis and antigen receptor function in t and b cells following exposure to herpes simplex virus.t cells are an essential component of the immune response against herpes simplex virus (hsv) infection. we previously reported that incubation of t cells with hsv-infected fibroblasts inhibits subsequent t cell antigen receptor signal transduction. in the current study, we found that incubation of t cells with hsv-infected fibroblasts also leads to apoptosis in exposed t cells. apoptosis was observed in jurkat cells, a t cell leukemia line, and also in cd4(+) cells isolated from human peripheral ...200717067652
herpes simplex virus blocks apoptosis by precluding mitochondrial cytochrome c release independent of caspase activation in infected human epithelial cells.expression of hsv-1 genes leads to the induction of apoptosis in human epithelial hep-2 cells but the subsequent synthesis of infected cell protein prevents the process from killing the cells. thus, viruses unable to produce appropriate prevention factors are apoptotic. we now report that the addition of either a pancaspase inhibitor or caspase-9-specific inhibitor prevented cells infected with an apoptotic hsv-1 virus from undergoing cell death. this result indicated that hsv-1-dependent apopto ...200717080326
evaluation of gamma-interferon kinetics in hsv-1 infected mice in different days post infection (in vivo) and post re-stimulation (in vitro).gamma interferon (ifn-gamma) is among the most important immune factors for limiting of herpes simplex virus (hsv) infections. however, our knowledge about the kinetics of ifn-gamma production after hsv infection is limited. the present study examines the kinetics of ifn-gamma expression following secondary infection with hsv-1. using semiquantitative rt-pcr assay, the expression of ifn-gamma in spleen lymphocytes was significantly detected on 14 days but not 7 days after intraperitoneal inocula ...200717098286
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
purification and identification of antiviral components from laggera pterodonta by high-speed counter-current chromatography.although laggera pterodonta, a folk medicine has been widely used for several centuries as an antiviral agent, there have been no studies to identify its antiviral components. a bioassay-guided phytochemical examination of l. pterodonta disclosed that its aqueous extract, which was made up of three dicaffeoylquinic acids showed significant inhibitory activity of virus replication. then a simple and efficient preparative high-speed counter-current chromatography (hsccc) method was successfully es ...200717920342
rise in seroprevalence of herpes simplex virus type 1 among highly sexual active homosexual men and an increasing association between herpes simplex virus type 2 and hiv over time (1984-2003).herpes simplex virus type 1 and type 2 (hsv-1 and hsv-2) are both highly prevalent. the rate of genital hsv-1 transmission is reportedly increasing over time. hsv-2 is considered to be an important risk factor for hiv transmission. we therefore studied changes in the hsv-1 and hsv-2 prevalence in a large cohort of men who have sex with men (msm) over a 20-year time period.200717929177
an update on short-course episodic and prevention therapies for herpes genitalis.the prevalence of herpes genitalis (genital herpes) has increased markedly over the past three decades. the most common cause is infection with the herpes simplex virus type 2 (hsv-2), but it can also occur as a result of hsv-1 infection. herpes genitalis can cause substantial psychosexual as well as physical morbidity and, in immunocompromised individuals, such as those who are hiv-positive, hsv infection can result in severe disease with progressive and extensive lesions. the natural history o ...200717877886
divergence and recombination of clinical herpes simplex virus type 2 isolates.herpes simplex virus type 2 (hsv-2) infects the genital mucosa and is one of the most common sexually transmitted viruses. here we sequenced a segment comprising 3.5% of the hsv-2 genome, including genes coding for glycoproteins g, i, and e, from 27 clinical isolates from tanzania, 10 isolates from norway, and 10 isolates from sweden. the sequence variation was low compared to that described for clinical hsv-1 isolates, with an overall similarity of 99.6% between the two most distant hsv-2 isola ...200717881457
fold recognition insights into function of herpes icp4 protein.icp4 is an important factor regulating the life cycle of hsv1. this conserved protein has several molecular functions, including activation of expression of viral late gene transcripts and inhibition of immediate early genes. although icp4 and its alphaherpesvirinae homologs (eg.: ie62 of vzv) have been subjects of various molecular studies, a complete view of their molecular function is lacking. here we present the results of fold recognition and molecular modelling of icp4 functional domains. ...200717882324
rethinking herpes simplex virus infections in children and adolescents. 200717889063
il-18, but not il-12, regulates nk cell activity following intranasal herpes simplex virus type 1 infection.infection of the respiratory tract with hsv type 1 (hsv-1) can have severe clinical complications, yet little is known of the immune mechanisms that control the replication and spread of hsv-1 in this site. the present study investigated the protective role of il-12 and il-18 in host defense against intranasal hsv-1 infection. both il-12 and il-18 were detected in lung fluids following intranasal infection of c57bl/6 (b6) mice. il-18-deficient (b6.il-18(-/-)) mice were more susceptible to hsv-1 ...200717709537
dna polymerase mutations in drug-resistant herpes simplex virus mutants determine in vivo neurovirulence and drug-enzyme interactions.mutations in the thymidine kinase and dna polymerase genes of herpes simplex virus (hsv) might confer resistance to antiviral drugs, particularly in immunocompromised patients who suffer from chronic and/or disseminated lesions. the patterns of cross-resistance and neurovirulence in mice of several dna polymerase mutants selected under pressure of foscarnet (pfa) and different acyclic nucleoside phosphonates (anps), including (s)-3-hydroxy-2-phosphonylmethoxypropyl (hpmp) derivatives of adenine ...200717713155
effect of prophylactic oral acyclovir after penetrating keratoplasty for herpes simplex keratitis.to determine the effect of routine use of prophylactic oral acyclovir after penetrating keratoplasty (pk) for herpes simplex virus (hsv) keratitis on recurrence, rejection, and graft failure rates.200717721290
apolipoprotein e genotype influences vertical transmission of herpes simplex virus type 1 in a gender specific manner.there is growing evidence that herpes simplex virus type 1 (hsv-1), together with the apolipoprotein e 4 (apoe4) allele, contribute to the pathogenesis of alzheimer's disease (ad), although the mechanism of their interaction remains uncertain. here we show that the combination of inherited apoe genotype and vertical transmission of hsv-1 confers a differential risk of brain infection. these risk factors are known to be associated with ad.200717725689
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