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unique spectrum of activity of 9-[(1,3-dihydroxy-2-propoxy)methyl]-guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1.a guanosine analog, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (dhpg), was found to inhibit herpes simplex virus type 1 (hsv-1), herpes simplex virus type 2, cytomegalovirus, and epstein-barr virus replication by greater than 50% at concentrations that do not inhibit cell growth in culture. the potency of the drug against all of these viruses is greater than that of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir). dhpg was active against hsv-1 growth during the early phase of virus replication an ...19836302704
effect of intensive acyclovir therapy during artificial reactivation of latent herpes simplex virus.the chemotherapeutic effect of intensive acyclovir (acv) treatment was evaluated in new zealand white rabbits with confirmed latent herpes simplex virus type 1 (hsv-1). acyclovir was administered orally (1 mg/ml of drinking water), topically (three times per day), and intramuscularly (16.5 mg/kg body wt twice per day) beginning 36 days after ocular inoculation and continued for 4 consecutive weeks, during which time the rabbits underwent concurrent stimulation by bilateral iontophoresis of 0.01% ...19836302707
inhibition of herpes simplex virus dna synthesis by pokeweed antiviral protein.pokeweed antiviral protein at a concentration of 3 microm inhibited both the synthesis and release of infectious herpes simplex virus type 1 in cell culture by 90 and 99%, respectively. addition of pokeweed antiviral protein to vero cell monolayers before virus infection was 10 to 15% more effective in reducing virus yields than was the simultaneous addition of the antiviral protein with virus inoculum. viral dna synthesis was inhibited by 90% in cells which had been exposed to the antiviral pro ...19836303210
possible molecular basis for antiviral activity of certain 5-substituted deoxyuridines.the antiviral activity of five structurally related pyrimidine nucleosides, e-5-propenyl-2'-deoxyuridine, 5-allyl-2'-deoxyuridine, e-5-(1-butenyl)-2'-deoxyuridine, 5-(2-butenyl)-2'-deoxyuridine, and 5-butyl-2'-deoxyuridine, in cell culture against herpes simplex virus type 1 was examined. analogs in which the c-c double bond of the 5-substituent was in conjugation with the pyrimidine ring were more potent antiviral drugs than were the corresponding nonconjugated and alkyl-substituted analogs. di ...19836303212
incorporation of 5-substituted analogs of deoxycytidine into dna of herpes simplex virus-infected or - transformed cells without deamination to the thymidine analog.the incorporation into dna of 5-bromocytosine and 5-iodocytosine, derived from their respective administered deoxyribonucleoside analogs, has been demonstrated in studies with cells infected with herpes simplex virus types 1 and 2 (hsv-1 and hsv-2) and in cells transformed with the thymidine kinase gene of hsv-1. no significant incorporation of iodocytosine or iodouracil occurred in the dna of uninfected or nontransformed cells when the deaminating enzymes were inhibited, in accord with past stu ...19836303214
characterization of mutants of herpes simplex viruses, types 1 and 2, that produce fragments of the thymidine kinase polypeptide.seven tk- mutants of herpes simplex virus, type 2 (hsv-2), and three tk- mutants of herpes simplex virus, type 1 (hsv-1), were isolated which did not produce the thymidine kinase (tk) polypeptides but formed smaller polypeptides not seen in wild-type infected cells. positive tk mrna selection by hybridization to the cloned tk genes followed by in vitro translation identified the tk polypeptides. comparisons of the products of partial proteolysis of the polypeptides of four hsv-2 and two hsv-1 tk ...19836303540
protective immunization of mice with specific hsv-1 glycoproteins.two herpes simplex virus type 1 (hsv-1) antigens of apparent molecular weight 123,000 and 63,000 which are associated with the viral glycoprotein complex have been identified and purified using virus-specific monoclonal antibodies. mice immunized with either glycoprotein showed marked resistance to challenge with virulent hsv-1. therefore purified glycoproteins of hsv-1 free of nucleic acid can be used in protective immunization of mice against human herpes simplex type 1.19836303950
correlation between low natural killing of fibroblasts infected with herpes simplex virus type 1 and susceptibility to herpesvirus infections.natural killer cells capable of lysing herpes simplex virus type 1 (hsv-1)-infected fibroblasts were studied in three groups of patients unusually susceptible to severe herpes-virus infections. cord blood was evaluated because of the known susceptibility of neonates to disseminated infections due to herpes simplex virus type 2 at birth. only 30% of the cord blood specimens tested demonstrated normal lysis of hsv-1-infected fibroblasts and a normal increment in the lysis of infected over uninfect ...19836304202
ultrastructural characterization of herpes simplex virus type 1 (strain 17) temperature-sensitive mutants.we report the ultrastructural features associated with wild-type and temperature-sensitive (ts) mutant infection at non-permissive temperature for each of 18 herpes simplex virus type 1 (hsv-1) (strain 17) ts mutants. the mutants were classified by their ability to induce nucleocapsid-related structures: class i failed to induce any, class ii induced empty and partially filled structures while class iii induced all of the identified structures including those containing an electron-dense core. t ...19836304234
herpes simplex virus-induced ribonucleotide reductase: development of antibodies specific for the enzyme.we have previously reported on the characterization of a novel ribonucleotide reductase induced in herpes simplex virus type 2 (hsv-2)-infected mammalian cells. the virus-induced enzyme was partially purified, free of the constitutive cell isozyme, by fractionation of infected cell extracts with ammonium sulphate. in this report we describe a further purification of the virus-induced enzyme and the development of a rabbit antiserum capable of specifically inhibiting its activity. enzymically act ...19836304235
alterations in substrate specificity and physicochemical properties of deoxythymidine kinase of a drug-resistant herpes simplex virus type 1 mutant.the deoxythymidine kinase (dtk) activity of a 5-methoxymethyldeoxyuridine-resistant mutant (mmdu(r)-20) of herpes simplex virus type 1 was compared with that of the parental wild-type (wt) virus. the dtk activity induced by the mutant was consistently less than that induced by the wt virus, was inhibited by antibody specific for herpes simplex virus dtk, and was more thermostable than the wt dtk. further, it was inhibited to a lesser degree than the wt dtk by the nucleoside analogs mmdu and arab ...19836304349
thermolabile in vivo dna-binding activity associated with a protein encoded by mutants of herpes simplex virus type 1.the major dna-binding protein encoded by several temperature-sensitive mutants of herpes simplex virus type 1 was thermolabile for binding to intracellular viral dna. the ability of dnase i to release this protein from isolated nuclei was used as a measure of the amount of protein bound to viral dna. this assay was based upon our previous observation that the fraction of herpesviral dna-binding protein which can be eluted from nuclei with dnase i represents proteins associated with progeny viral ...19836304350
preparation of a "functional library" of african green monkey dna fragments which substitute for the processing/polyadenylation signal in the herpes simplex virus type 1 thymidine kinase gene.fragments of african green monkey (cercopithecus aethiops) dna (3.5 to 18.0 kilobases) were inserted downstream from the thymidine kinase (tk, tk) coding region in ptk206/sv010, a gene construct which lacks both copies of the hexanucleotide 5'-aataaa-3' and contains a simian virus 40 origin of replication, allowing it to replicate in cos-1 cells. no polyadenylated tk mrna was detected in cos-1 cells transfected by ptk206/sv010. the ability of simian dna fragments to restore tk gene expression wa ...19836304500
functional analysis of a herpes simplex virus type 1 promoter: identification of far-upstream regulatory sequences.we have performed a functional analysis of dna sequences upstream from the gene for ie mrna3 of herpes simplex virus type 1. nucleotide sequences involved in initiation and positive regulation of transcription have been defined by construction of specific deletions in vitro. transcription was assayed in vivo by microinjection into xenopus oocytes, or by introduction of plasmid dna into tissue culture cells and measurement of transient expression. three functional promoter elements have been defi ...19836304649
herpes simplex virus glycoprotein d: human monoclonal antibody produced by bone marrow cell line.normal bone marrow cells from a donor positive for herpes simplex virus were transformed with epstein-barr virus. the resulting lymphoblastoid cell line has secreted immunoglobulin g1 of the kappa type continuously for 2 years. this immunoglobulin, detected both on the cell surface and in the cytoplasm, reacts with cells infected with herpes simplex virus. it defines an antigen that comigrates with the 55-kilodalton glycoprotein d of herpes simplex virus type 1 and neutralizes the infectivity of ...19836304881
herpes simplex virus and human cancer. iii. search for relationship of herpes simplex antibodies and cervical dysplasia and labial neoplasia.we employed the enzyme-linked immunosorbent assay (elisa), indirect hemagglutination (iha), and complement fixation (cf) methods to measure antibody titer to herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) in patients affected by labial tumors or cervical dysplasias. no relationship of antibody titer to hsv-1 and labial tumors was detected by any of the three methods. association between antibody titer to hsv-2 and cervical dysplasias was revealed by iha (p less than 0.05) and elisa (p le ...19836304957
herpes simplex virus latency and reactivation in isolated rat sensory neurons.an in vitro herpes simplex virus type 1 (hsv-1) latency model has been established using neurons isolated from dissociated rat fetus sensory ganglia as the host cell. rat fetal neuron cells were pretreated for 24 hr at 37 degrees with (e)-5-(2-bromovinyl)-2'-deoxyuridine and human leukocyte interferon, infected with hsv-1 (approximately 2.5 plaque-forming units/cell), and treated for 7 days with the same inhibitor combination. infectious hsv-1 became undetectable 3 days postinfection and remaine ...19836305013
localization of the regions of homology between the genomes of herpes simplex virus, type 1, and pseudorabies virus.only 8% of the sequences of the genomes of pseudorabies (prv) and herpes simplex (type 1) (hsv) viruses are homologous. these homologous sequences have been shown previously to be distributed throughout most of the genomes of the two viruses. by means of blot hybridization of restriction fragments of hsv-1 dna to cloned, nick-translated restriction fragments of prv dna, it was possible to compare the location on the genomes of these viruses of the homologous regions. the results showed that the ...19836305015
effect of several antiviral agents on human lymphocyte functions and marrow progenitor cell proliferation.toxicity to hematopoiesis and lymphocytic function are major considerations in the clinical applicability of antiviral agents. we have examined the toxicities of five antiviral agents showing activity against herpesviruses: vidarabine, acyclovir, (e)-5-(2-bromovinyl)-2'-deoxyuridine, trifluorothymidine, and (s)-9-(2,3-dihydroxypropyl)adenine. the drugs were tested in vitro for inhibition of herpes simplex virus type 1 and human cytomegalovirus replication, effects on marrow progenitor cell growt ...19836305264
a low thymidine kinase-producing mutant of herpes simplex virus type 1 causes latent trigeminal ganglia infections in mice.the wild type nih strain of herpes simplex virus type 1 (hsv-1) has a mixed plaque morphology of both large and small plaques. from this virus we selected a large plaque isolate that was a high producer of thymidine kinase (tk) activity (designated tk+) and a small plaque isolate that produced 25 per cent of the tk activity of the large plaque mutant (designated tk 1/4). a tk- mutant of the large plaque virus was obtained after passage of the virus in the presence of budr. the pathogenicity of t ...19836305312
recovery from lethal herpes simplex virus type 1 infection is mediated by cytotoxic t lymphocytes.the ability of herpes simplex virus (hsv)-specific, cytotoxic t lymphocytes to mediate recovery of mice lethally infected with hsv was examined. adoptive transfer of splenocytes from mice that had been primed in vivo with hsv and restimulated with hsv in vitro protected lethally infected normal and cyclophosphamide-immunosuppressed mice from death. in contrast, equal numbers of normal splenocytes or immune splenocytes cultured without antigen failed to mediate recovery. recovery was also transfe ...19836305838
isolation of human cytomegalovirus dna from infected cells.human cytomegalovirus (hcmv) dna was extracted from infected human embryo fibroblast cultures using the hirt, triton-nacl, and total extraction methods. the hirt method gave a maximum yield of 60% and was 5- to 10-fold more efficient than the triton-nacl method for the extraction of hcmv dna. however, both methods gave comparable yields ranging from 70 to 75% for the extraction of herpes simplex virus type 1 (hsv1) dna from infected cells. the hirt-extracted hcmv dna contained from 5 to 10% cont ...19836305866
virus-host cell interaction in rat c6 glial cell cultures persistently infected with herpes simplex virus.the virus-host cell interaction in a rat c6 glial cell line persistently infected with herpes simplex virus type 1 (hsv1) was examined. the c6 cultures infected at an moi of 10 or 0.01 exhibited virally induced cytopathology and produced infectious virus and viral antigens for 108 and 50 days, respectively. infectious virus was continually present in the supernatant fluids of persistently infected cultures, with only a minority of the cells having viral cpe or viral antigens at any given time. t ...19836305868
a novel method for determining the sensitivity of herpes simplex virus to antiviral compounds.a rapid and sensitive assay was developed to analyse the sensitivity of wild type hsv-1 and hsv-2 isolates with respect to a battery of antiviral substances. in the viral sensitivity assay, human embryonic lung fibroblasts are incubated with the virus isolate and different concentrations of the antivirals. after 1-3 days, the cells are disrupted and analysed for hsv type 1 or 2 antigens by an enzyme-linked immunosorbent assay. antigens corresponding to 17 plaque-forming units were detectable aft ...19836306030
inhibition of herpes simplex virus replication by cobra alpha-neurotoxoid.a peptide, prepared by gentle oxidative detoxification of a methionine-free cobra alpha-neurotoxin, was evaluated for antiviral activities in vivo and in vitro. when added to bhk cells before infection the peptide reduced herpes simplex virus type 1 (hsv-1)-induced tcd50 in a dose- and time-dependent manner. the antiviral effect was also expressed on initiation of cell treatment 1 h after infection if the peptide was left in contact with cells. single, intracerebral doses of the toxoid in suckli ...19836306147
variation in resistance of cells from inbred strains of mice to herpes simplex virus type 1.by several criteria, replication of herpes simplex virus type 1 (hsv-1) in primary cell cultures from inbred strains of mice resistant (r) to this virus was less than in cultures from susceptible (s) strains. the difference was not obviously related to less efficient adsorption, to more efficient production of interferon or to a larger number of lysosomes. except at high multiplicities of infection, cells from the f1 progeny of a cross between an r and an s strain replicated virus as well as cel ...19836306148
virus polypeptide synthesis induced by herpes simplex virus in non-permissive rat xc cells.the synthesis of virus polypeptides in rat xc cells infected with herpes simplex virus type 1 (hsv-1; 13vb4tsc75) was studied. at the permissive temperature the virus induced the synthesis, in a cascade fashion, of significant amounts of several early polypeptides (icp 6, 8 and 39) and those late polypeptides that are relatively resistant to inhibition by phosphonoacetic acid in hep2 cells (icp 5, 11, 25, 29, 43 and 44). the infectious cycle appeared to become arrested in xc cells at about 7 to ...19836306150
replication of herpes simplex virus type 1 on hydroxyurea-resistant baby hamster kidney cells.hydroxyurea-resistant (hur) baby hamster kidney cells were isolated, subcloned, and characterized. one clonal line, which contained elevated levels of ribonucleotide reductase, lost its hu resistance during passage in the absence of the inhibitor, whereas another clonal line was stably resistant. the replication of herpes simplex virus type 1 on these cells was compared with that of the parvovirus minute virus of mice. herpes simplex virus type 1 was found to be as sensitive to hu on both lines ...19836306274
fatal disseminated herpes simplex virus type 1 infection in a child receiving acth: failure of vidarabine therapy. 19836306609
9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine: a selective inhibitor of herpes group virus replication.9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine (2'-nor-2'-deoxyguanosine; 2'ndg) selectively inhibits the replication of herpes group viruses. in cell culture studies 2'ndg was at least 10-fold more potent than acyclovir (acv) in inhibition of human cytomegalovirus replication and epstein-barr virus-induced lymphocyte transformation and was about as effective as acv in inhibition of herpes simplex viruses 1 and 2 and varicella zoster virus. orally administered 2'ndg was 6- to 50-fold more ...19836306664
the effects of dietary t-2 toxin on the immunological function and herpes simplex reactivation in swiss mice.t-2 toxin, a trichothecene mycotoxin, is a potently cytotoxic and immunosuppressive secondary metabolite produced by fusarium fungi. young male white swiss mice were fed a diet supplemented with t-2 toxin at levels of 5, 10, or 20 ppm, control diet ad libitum, or control diet at a restricted rate for 1, 2, 3, 4, and 6 weeks. the effect of the toxin on the immune system of these mice was assessed by counting total spleen cell numbers and the in vitro proliferative response of spleen cells from th ...19836306870
monoclonal antibodies for rapid diagnosis and typing of genital herpes infections during pregnancy.fluorescein-conjugated, type-specific monoclonal antibodies to herpes simplex virus (hsv-1 and hsv-2) and group-specific antibody which recognizes both hsv-1 and hsv-2 were used to detect hsv-infected cells in clinical specimens. specimens were collected from 66 pregnant women with a past history of herpes genitalis or with suspected lesions. fourteen of 18 samples from which virus was isolated were positive by immunofluorescence test; four of 18 specimens had an insufficient number of cells (le ...19836307053
susceptibility of recent clinical isolates of herpes simplex virus to 5-ethyl-2'-deoxyuridine: preferential inhibition of herpes simplex virus type 2.we examined the in vitro susceptibilities of three reference strains and 41 recent clinical isolates of herpes simplex virus types 1 and 2 to 5-ethyl-2'-deoxyuridine. this thymidine analog exerts a type 2-preferential but not a type 2-specific antiviral effect. utilizing a microtiter assay with bhk-21 cells, we found that the mean (+/- standard deviation) 50% inhibitory dose for herpes simplex virus type 1 isolates was 0.58 +/- 0.30 micrograms/ml as compared with 0.33 +/- 0.20 microgram/ml for h ...19836307130
antiviral activity of the 3'-amino derivative of (e)-5-(2-bromovinyl)-2'-deoxyuridine.3'-nh2-bv-durd, the 3'-amino derivative of (e)-5-(2-bromovinyl)-2'-deoxyuridine, was found to be a potent and selective inhibitor of herpes simplex virus type 1 (hsv-1) and varicella-zoster virus (vzv) replication. 3'-nh2-bv-durd was about 4-12 times less potent but equally selective in its anti-herpes activity as bv-durd. akin to bv-durd, 3'-nh2-bv-durd was much less inhibitory to herpes simplex virus type 2 than type 1. it was totally inactive against a thymidine kinase-deficient mutant of hsv ...19836307280
detection in antisera of antibodies that cross-react with herpes simplex virus type 1 glycoprotein gc.herpes simplex virus type 1 (hsv-1) glycoprotein gc was purified by affinity chromatography with an immunosorbent column containing monoclonal antibody to hsv-1 gc, and its reactivity with rabbit antisera was measured by enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of radioimmunoprecipitates. positive reactions were detected between hsv-1 gc and rabbit hyperimmune antisera to both hsv-1 and hsv-2. electrophoretic analysis also revealed ...19836307870
comparison of effects of adjuvants on efficacy of virion envelope herpes simplex virus vaccine against labial infection of balb/c mice.a subunit virion envelope vaccine of herpes simplex virus type 1 was evaluated for its ability to protect labially infected mice from development of the primary herpetic lesion, encephalitic death, and latent virus infection in the trigeminal ganglion. several adjuvants, including aluminum hydroxide and polyriboinosinic acid-polyribocytidylic acid complexed with poly-l-lysine and carboxymethyl cellulose were investigated for their ability to enhance protection of the subunit vaccine and were com ...19836307874
blocked herpes simplex virus type 2-specific dna synthesis in simian virus 40-transformed hamster cells permissive for herpes simplex virus type 1.simian virus 40-transformed hamster cells (ll-1) permissive to herpes simplex virus type 1 (hsv-1) were shown to be relatively nonpermissive to hsv-2. when ll-1 cells were infected with hsv-2, there was a 3- to 4-log reduction in infectious viral progeny at 24 h postinfection as compared with hsv-1 under identical cultured conditions. hsv-2 could be carried in the ll-1 cell line for up to 12 passages without any appreciable cytopathology. various early functions of the replicative cycle of hsv-2 ...19836307875
colonization of murine ganglia by a superinfecting strain of herpes simplex virus.we report on the colonization of murine trigeminal ganglia after sequential infection of mice by herpes simplex viruses (hsvs). in preliminary studies, we have established that whereas the hsv-1(f) strain efficiently colonizes ganglia when inoculated by either the ear or eye routes, the hsv-1 x hsv-2 recombinant c7d colonizes ganglia when inoculated by the eye route only. the experimental design consisted of inoculating the right eye with c7d on day 1 and with hsv-1(f) in both left and right eye ...19836307880
effect of the ionophore monensin on herpes simplex virus type 1-induced cell fusion, glycoprotein synthesis, and virion infectivity.the ionophore monensin inhibited the formation of mature, fully glycosylated glycoproteins gb, gc, and gd during herpes simplex virus type 1 infection of human embryonic lung cells. underglycosylated forms, including the apparent high-mannose precursor forms of the major glycoproteins, appeared. monensin inhibited virus-induced cell fusion. infectious virions produced in the presence of monensin appeared to contain predominantly underglycosylated glycoproteins.19836307921
an elisa technique to detect igg antibody to the early herpes simplex virus type 2 (hsv-2) antigen ag-4 in hsv-2 patients.an elisa system, based on urease activity was used for the detection and titration of igg to the immediate early ag-4 antigen in sera from hsv-2 patients. it detected low levels of igg to the ag-4 antigen in 32% of patients' sera known to contain complement fixing antibody to the antigen. furthermore, the sensitivity of the elisa system was 2- to 10-fold higher than the complement-fixation system depending on when the sera was taken from the hsv-2 patients. the system also allowed the easy detec ...19836308025
eclipse of coxsackievirus infectivity: the restrictive event for a non-fusing myogenic cell line.coxsackieviruses a2, a5 and b3 did not replicate in l8cl3-u cells (a non-fusing variant of the rat l8 myogenic cell line) although these cells possessed a common receptor for coxsackieviruses a2 and a5, and a different receptor for coxsackievirus b3. the restriction in replication was identified as a block in viral eclipse, since 6 m-licl treatment permitted recovery of the coxsackievirus a2 inoculum from l8cl3-u cells after 2 h at 37 degrees c, and the cells could be transfected by viral rna. c ...19836308134
specific herpes simplex virus antigen in human gingiva.herpes simplex virus type 1 (hsv-1) specific antigens were found to be present in the sulcular epithelial cells of patients that were undergoing periodontal treatment. four out of 14 cases were positive to specific hsv-1 antigen, as demonstrated by the indirect immunofluorescent assay. no nuclear staining was seen in any epithelial cells. these observations seem to indicate that the viral genome resides in the sulcular epithelial cells of the gingiva and is possibly localized in the stratum gran ...19836308203
detection of virus-specific rna in herpes simplex virus type 1-transformed hamster cell lines.in situ hybridization experiments with the use of recombinant herpes simplex virus type 1 dna as probes have detected virus-specific rna in herpes simplex virus type 1-transformed syrian hamster cell lines. the relatively most abundant virus transcripts hybridized to the herpes simplex virus type 1 ecori-f fragment at map position 0.32-0.42.19836308323
bovine papilloma virus contains an activator of gene expression at the distal end of the early transcription unit.bovine papilloma virus (bpv) contains a cis-acting dna element which can enhance transcription of distal promoters. utilizing both direct and indirect transient transfection assays, we showed that a 59-base-pair dna sequence from the bpv genome could activate the simian virus 40 promoter from distances exceeding 2.5 kilobases and in an orientation-independent manner. in contrast to the promoter 5'-proximal localization of other known viral activators, this element was located immediately 3' to t ...19836308425
a dna topoisomerase activity copurifies with the dna polymerase induced by herpes simplex virus.a dna-relaxing enzyme was found to copurify along with herpes simplex virus type i (hsv-1)-induced dna polymerase throughout a multistep purification scheme. both the enzymes had similar sedimentation velocity, required high ionic strength for optimal enzymatic activities and showed time dependence of reaction. the dna-relaxing enzyme however, differed from the hsv-1 dna polymerase in its requirement for higher mg2+ concentration, ratp and much broader ph dependence. furthermore, phosphonoacetic ...19836309234
phase i evaluation of 2'-fluoro-5-iodo-1-beta-d-arabinofuranosylcytosine in immunosuppressed patients with herpesvirus infection.2'-fluoro-5-iodo-1-beta-d-arabinofuranosylcytosine (fiac) is a potent selective inhibitor of the replication of herpes simplex virus types 1 and 2 (hsv-1, hsv-2), varicella zoster virus, and cytomegalovirus in cell culture systems. fiac produces an unequivocal therapeutic effect in mice that have been inoculated with a lethal burden of hsv-1. we have administered fiac to 32 host compromised patients, 30 with advanced cancer, who were experiencing acute herpesvirus infections (varicella zoster, 2 ...19836309380
ribonucleotide reductase induced by herpes simplex type 1 virus. characterization of a distinct enzyme.the ribonucleotide reductase induced by herpes simplex virus type 1 (hsv-1) was purified in high yield from serum-starved baby hamster kidney (bhk-21) cells infected with hsv-1 (strain h-29). the enzyme preparation was essentially free of both eucaryotic ribonucleotide reductase and contaminating enzymes that could cause significant depletion of substrates. the hsv-1-induced enzyme was assayed in 0.2 m 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid-na at the ph optimum of 8.1 and the optimal ...19836309786
location and orientation of homologous sequences in the genomes of five herpesviruses.molecular hybridization experiments were carried out to investigate homologous regions in the genomes of herpes simplex virus types 1 and 2 (hsv-1 and hsv-2), equid herpesvirus 1 (ehv-1), pseudorabies virus (prv) and varicella-zoster virus (vzv). virion dna probes from ehv-1, prv and vzv hybridized to similar regions of the hsv genome, and the use of cloned dna probes allowed heterologous genomes to be oriented with respect to homologous regions. the hsv-1 and hsv-2 genomes are colinear, the ehv ...19836310033
processing of glycoproteins induced by herpes simplex virus type 1: sulphation and nature of the oligosaccharide linkages.using the drug tunicamycin we have investigated the nature of the oligosaccharides on herpes simplex virus type 1 (hsv-1)-induced glycoproteins e and y (gy is a newly identified glycoprotein which has the same apparent mol. wt. as gc but a more basic isoelectric point). synthesis of both glycoproteins was inhibited by the drug, suggesting they contain n-linked oligosaccharides. our finding, combined with the previous results of other workers, suggests that all the major hsv-induced glycoproteins ...19836310034
the effect of cycloheximide on the accumulation and stability of functional alpha-mrna in cells infected with herpes simplex virus.cells were infected with herpes simplex virus type 2, hsv-2(g), and incubated in the presence of cycloheximide (cx). when cx was removed and actinomycin d (act d) added, alpha-polypeptides icp 0 and icp 4 were synthesized at low rates. if cx was removed without adding act d, the rate of production of icp 4 increased while that of icp 0 remained constant. in cells treated with azetidine to enhance the production of icp 4 and 0, accumulation of functional mrna for icp 4 (determined indirectly by t ...19836310035
delayed igg-mediated clearance of herpes simplex virus type 1 from the cns but not footpad during the early stages of infection: possible result of relative integrity of the blood-brain barrier.following footpad inoculation in mice, herpes simplex virus type 1 spreads along nerves to the spinal cord where a myelitis causes hind limb paralysis beginning on day 6. neutralizing antibody effectively prevents this illness only if given within 72 h. we therefore studied the timing of blood-brain barrier (bbb) disruption relative to the appearance of virus and inflammatory cell infiltrates in the spinal cord. virus was detectable in dorsal root ganglion and spinal cord explants by 48 h. by 72 ...19836310036
neuropathogenicity of herpes simplex virus in mice: protection against lethal encephalitis by co-infection with a non-encephalitogenic strain.intraperitoneal infection of susceptible mice with an apathogenic herpes simplex virus type 1 (hsv-1) strain prevented the lethal outcome of a challenge infection with a pathogenic strain, even if the challenge preceded the protective infection. it was found that the protective inoculation blocks the initial replication of the challenge virus. in addition, intraperitoneal infection with the protective hsv-1 strain led to the induction of a refractory state in the central nervous system, resultin ...19836310037
effects of monoclonal antibodies directed against herpes simplex virus-specified glycoproteins on the generation of virus-specific and h-2-restricted cytotoxic t-lymphocytes.passive transfer of monoclonal antibodies specific for herpes simplex virus type 1 (hsv-1) glycoproteins gc or gd resulted in the generation of highly potent hsv-specific and h-2-restricted primary cytotoxic t-lymphocytes (ctl) in the lymph nodes of recipients provided they were injected at 12 h post-infection. when the same antibody was injected at 3 h before hsv infection, the recipients failed to generate primary anti-hsv ctl. rather, lymph node cells from such donors proved unsuitable for th ...19836310041
n-acetylgalactosaminyltransferase activity involved in o-glycosylation of herpes simplex virus type 1 glycoproteins.we report on n-acetylgalactosaminyltransferase (udpacetylgalactosamine--protein acetylgalactosaminyltransferase; ec 2.4.1.41) activity in herpes simplex virus type 1 (hsv-1)-infected bhk and ricr14 cells, a line of ricin-resistant bhk cells defective in n-acetylglucosaminyltransferase i. the enzyme catalyzed the transfer of [14c]n-acetylgalactosamine (galnac) from udp-[14c]galnac into hsv glycoproteins, as identified by immunoprecipitation. the sugar was selectively incorporated into the immatur ...19836310156
herpes simplex keratitis.avirulent strains of herpes simplex type 1 (hsv-1) infect and shed and colonize the ganglia in rabbits. this primary infection reduces the severity of subsequent infection by virulent virus and prevents ganglionic colonization by even very virulent neurotropic virus. only a small proportion of the human population known to be infected with hsv-1 develops clinical disease. it is possible that the severity and likelihood of recurrence of this disease is determined by the virulence of the original ...19836310466
an outbreak of herpes simplex virus type 1 in an intensive care nursery.neonatal herpes simplex infection is not a common occurrence but one which warrants particular concern. an 1800-g premature infant who developed respiratory distress and died at 12 days unexpectedly yielded hsv from a culture of cerebrospinal fluid. there were no mucocutaneous lesions. ten days later three other infants (ages 40, 69 and 11 days) developed vesicles which yielded herpes simplex. health care staff cohorts were assigned to "clean" or "exposed" nursery areas. the three secondarily in ...19836310534
encapsidation sequences for spleen necrosis virus, an avian retrovirus, are between the 5' long terminal repeat and the start of the gag gene.the minimal cis-acting sequences outside the long terminal repeat (ltr) required for formation of an infectious retrovirus cloning vector were determined with recombinants of spleen necrosis virus (snv) dna and herpes simplex virus type 1 thymidine kinase gene. the 3' end of snv dna was removed to within 40 base pairs (bp) from the 3' ltr with only a 2-fold effect on the recovery of infectious recombinant virus. however, when the 5' end of snv dna was removed to within 100 bp from the 5' ltr, in ...19826310558
biology of simian virus 40 (sv40) transplantation antigen (trag). ix. analysis of trag in mouse cells synthesizing truncated sv40 large t antigen.mouse ltk- cells (h-2k) were transfected with a series of recombinant plasmids consisting of the herpes simplex virus type 1 thymidine kinase (tk) gene linked to fragments of sv40 dna coding for portions of sv40 t antigen in pbr322, and tk+ transformants (ltk+) were selected in hat medium. the tk+ transformants were analyzed for sv40 transplantation rejection antigen (trag) at the cell surface by reacting them with cytotoxic lymphocytes (ctl) generated to sv40 trag in c3h/hej (h-2k) mice. the re ...19836310860
anti-gd monoclonal antibodies inhibit cell fusion induced by herpes simplex virus type 1.monoclonal antibodies directed against glycoprotein d of herpes simplex virus completely inhibited fusion of vero cells infected with type 1 virus. in contrast, several monoclonal antibodies directed against other viral glycoproteins, including b, were ineffective or were only minimally inhibitory at the highest concentrations tested.19836310880
activity of 1-(2'-fluoro-2'-deoxy-beta-d-arabinofuranosyl)thymine against herpes simplex virus in cell cultures and rabbit eyes.a new antiviral compound 1-(2'-fluoro-2'-deoxy-beta-d-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-uracil [fmau]), was compared with acyclovir and idoxuridine in vitro against two strains of both herpes simplex virus type 1 (hsv-1) and hsv-2. determinations of the 50% effective dose varied slightly with each strain and with the host cells employed. the 50% effective dose for fmau and acyclovir against hsv-1 ranged from 0.1 microm to 0.5 to 0.6 microm in rabbit kidney cells and from 0.5 micro ...19836311085
susceptibility of phosphonoformic acid-resistant herpes simplex virus variants to arabinosylnucleosides and aphidicolin.a plaque-reduction assay was used to examine the susceptibility of five phosphonoformic acid-resistant variants of herpes simplex virus type 1 to arabinosylnucleosides and aphidicolin. these viruses were cross-resistant to arabinosylhypoxanthine and to arabinosyladenine when tested in the absence of deoxycoformycin, a deaminase inhibitor. in the presence of deoxycoformycin, no cross-resistance between arabinosyladenine and phosphonoformic acid was observed. the two variants tested were cross-res ...19836311091
herpes simplex virus infection of motor neurons: hypoglossal model.herpes simplex virus type 1 (hsv) was inoculated into the tongue muscle of a/j mice. typical hsv vesicles developed on the tongue surface 4 days after hsv inoculation. virus was isolated from hypoglossal nerve explants, and inflammatory cells appeared where the hypoglossal nerve exists from the ventral medulla. hsv viral capsids were present in astroglial cells near the point of nerve exit. a focal encephalitis ensued with immunoperoxidase staining of hsv antigens in neurons of the hypoglossal n ...19836311751
purification and characterization of herpes simplex virus (type 1) thymidine kinase produced in escherichia coli by a high efficiency expression plasmid utilizing a lambda pl promoter and ci857 temperature-sensitive repressor.the structural gene for herpes simplex virus (type 1) thymidine kinase was cloned downstream from the lambda phage high efficiency leftward promotor in a plasmid (phetk2) also containing the gene for the lambda ci857 temperature-sensitive repressor. thymidine kinase is synthesized as a run-on product containing the nh2 terminus of the lambda n protein. heat inactivation of the lambda repressor by growth at 42 degrees c results in the accumulation of thymidine kinase as approximately 4% of the to ...19836311815
determination of herpes simplex virus type-specific antibodies by enzyme-linked immunosorbent assay.we determined type-specific antibodies to herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) by an indirect enzyme-linked immunosorbent assay, using as antigens hsv-1 glycoprotein gc-1 and a hsv-2-specific polypeptide purified on affinity columns of monoclonal antibodies. all sera were initially screened for hsv antibodies by the enzyme-linked immunosorbent assay with a pool of triton x-100-extracted antigens of hsv-1- and hsv-2-infected hep-2 cells. the titer of hsv antibodies was predicted ...19836311871
relative titers of antibodies to individual polypeptide antigens of herpes simplex virus type 1 in human sera.human immune sera were analyzed by an immunoblot procedure in order to identify which polypeptides of herpes simplex virus type 1 were recognized and to determine the relative concentrations of antibodies to individual viral antigens. the strongest reactivity in all immune sera examined was directed against the three major herpes simplex virus-specific glycoprotein antigens (gab, gc, and gd) and a series of uncharacterized low-molecular-weight polypeptides. titers of antibody to the gc and gd an ...19836311910
herpes simplex virus non-structural proteins. iv. purification of the virus-induced deoxyribonuclease and characterization of the enzyme using monoclonal antibodies.the alkaline nucleases induced by herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) have been purified from high salt extracts of virus-infected cells. the purification used three types of column chromatography and resulted in apparently homogeneous dnase preparations with good recovery. the enzyme from hsv-2-infected cells has been characterized. it had both exonuclease and endonuclease activity, each with an unusually high ph optimum. the enzyme had an absolute requirement for magnesium w ...19836311954
physical mapping of temperature-sensitive mutations of herpes simplex virus type 1 using cloned restriction endonuclease fragments.sequences from the whole of the hsv-1 strain 17 genome were cloned into bacterial plasmid vectors, with the exception of part of bamhi v which was deleted in all cloned dnas spanning this region of the virus dna. the cloned dnas were used in intratypic marker rescue experiments to map temperature-sensitive (ts) mutations on to the virus genome. since the sequences of these dnas overlapped, any mutation could be rapidly assigned a physical map position. this approach is particularly useful for ma ...19836311955
an evaluation of certain chain-extended analogues of 9-beta-d-arabinofuranosyladenine for antiviral and cardiovascular activity.several nucleosides modified and chain extended at the 5'-position have been synthesized as follows: n6-benzamido- 9-(2,3-di-o-benzoyl-beta-d-arabino-pentodialdo-1,4-furanosyl)adenine, o=chr, a leads to (e)-etococh=chr (2) b leads to etococh2ch2r (3) c leads to h2ncoch2ch2r (6) d leads to 1-(adenin-9- yl)-1,5,6-trideoxy-beta-d-arabino-hepto-1,4-furanuronamide (8); 3 e leads to ethyl 1-(adenin-9-yl)-1,5,6-trideoxy-beta-d-arabino-hepto-1, 4-furanuronate (5) f leads to 1-(adenin-9-yl)-1, 5,6-trideo ...19836312045
positive control of the herpes simplex virus thymidine kinase gene requires upstream dna sequences.we examined the ability of deleted versions of the herpes simplex virus type 1 thymidine kinase gene, present in biochemically transformed mouse cells, to be induced in trans to a higher level of expression by superinfecting herpes simplex virus immediate early gene products. the results demonstrate that sequences mapping between -200 and -80 and between -70 and -12 are required for induction. as these regions are largely coincident with the previously identified thymidine kinase gene promoter, ...19836312067
functional suppression in mammalian cells of nonsense mutations in the herpes simplex virus thymidine kinase gene by suppressor trna genes.a nonsense mutation (uag) in the thymidine kinase gene of herpes simplex virus type 1 can be suppressed in vivo to produce active thymidine kinase by prior infection with a defective simian virus 40 stock which acts as a vector to introduce a functional suppressor trna gene into mammalian cells in culture. the suppression is specific for uag, but not uga or missense, mutants and restores thymidine kinase activity to 20 to 40% of the wild-type level. these results suggest that many cell lines sus ...19836312072
mutations in the major dna-binding protein gene of herpes simplex virus type 1 result in increased levels of viral gene expression.we have examined the effect of temperature-sensitive mutations in the herpes simplex virus 1 dna-binding protein gene on viral gene expression. we have found that at the nonpermissive temperature, the synthesis of certain immediate early, early, and late viral polypeptides was greater in cells infected with the temperature-sensitive mutants than in cells infected with the wild-type virus. this effect was independent of the requirement for this viral protein for viral dna replication. the altered ...19836312079
genetic and phenotypic analysis of herpes simplex virus type 1 mutants conditionally resistant to immune cytolysis.nine temperature-sensitive (ts) mutants of herpes simplex virus type 1 selected for their inability to render cells susceptible to immune cytolysis after infection at the nonpermissive temperature have been characterized genetically and phenotypically. the mutations in four mutants were mapped physically by marker rescue and assigned to functional groups by complementation analysis. in an effort to determine the molecular basis for cytolysis resistance, cells infected with each of the nine mutan ...19836312082
class i defective herpes simplex virus dna as a molecular cloning vehicle in eucaryotic cells.defective herpes simplex virus type 1 genomes are composed of head-to-tail tandem repeats of small regions of the nondefective genome. monomeric repeat units of class i defective herpes simplex virus genomes were cloned into bacterial plasmids. the repeat units functioned as replicons since both viral and convalently linked bacterial plasmid dna replicated (with the help of dna from nondefective virus) when transfected into rabbit skin cells. recombinant plasmids were packaged into virions and w ...19836312096
insertion mutants of herpes simplex virus have a duplication of the glycoprotein d gene and express two different forms of glycoprotein d.we produced insertion mutants of herpes simplex virus (hsv) that contain two functional copies of genes encoding different forms of glycoprotein d (gd). these viruses have the gene for hsv type 2 (hsv-2) gd at the normal locus and the gene for hsv-1 gd inserted into the thymidine kinase locus. results of immunoprecipitation experiments done with monoclonal antibodies revealed that both gd genes were expressed by these viruses, regardless of orientation of the inserted hsv-1 gd gene, and that max ...19836312097
rnas transcribed from a 3.6-kilobase smai fragment of the short unique region of the herpes simplex virus type 1 genome.a 3.6-kilobase (kb) smai subclone of the bamhi j fragment of herpes simplex virus type 1 (kos) dna was utilized to characterize the mrnas transcribed from the genome segment (0.91 to 0.93 map units) that encodes glycoprotein d mrna. rna blotting demonstrated two major rna species of 2.3 and 1.5 kb. 5' and 3' mapping with 32p-end-labeled dna fragments indicated that these rnas are a nested set, each having its own promoter and 3' terminus. less abundant rna species with discrete 5' ends were also ...19836312102
detection of antibodies to herpes simplex virus with a continuous cell line expressing cloned glycoprotein d.the gene for glycoprotein d of herpes simplex virus type 1 (hsv-1) was expressed in stable mammalian cell lines. glycoprotein d produced in these cells has a number of antigenic determinants in common with the native glycoprotein. cell lines expressing glycoprotein d were used in an enzyme-linked immunosorbent assay to detect human antibodies to glycoprotein d. this strategy should prove useful in determining the extent to which the immune response to hsv-1 is directed toward glycoprotein d.19836312563
effects of (e)-5-(2-bromovinyl)-2'-deoxyuridine on the proliferation of herpes simplex virus type 1-transformed and thymidine kinase-deficient mouse cells.(e)-5-(2-bromovinyl)-2'-deoxyuridine (bvdu) is a highly selective inhibitor of herpes simplex virus-1 (hsv-1). a cell line (lh-1) expressing the hsv thymidine kinase (tk) gene is extremely sensitive to bvdu, whereas the parent line that expresses the cellular tk is resistant to bvdu. a tk-deficient derivative cell line (lmtk(-] which expresses neither the cellular nor viral tk was also extremely sensitive to bvdu. this suggests that the thymidine analog, bvdu, can be phosphorylated in thymidine ...19836312685
interferon susceptibility of herpes simplex virus strains isolated from patients enrolled in clinical trials.herpes simplex virus type 1 strains isolated from patients who had received interferon in a clinical trial were not more resistant to human leukocyte interferon than strains derived from recipients of a placebo. the susceptibility of herpes simplex virus type 2 strains isolated from herpes genitalis was slightly less than that of herpes simplex virus type 1 strains causing herpes genitalis.19836312872
antiherpetic activity and mechanism of action of 9-(4-hydroxybutyl)guanine.9-(4-hydroxybutyl)guanine was synthesized and tested for antiherpes activity. in cell cultures, different strains of herpes simplex virus type 1 (hsv-1) and type 2(hsv-2) were inhibited by 50% at 2-14 microm of 9-(4-hydroxybutyl)guanine, while a hsv-1 mutant lacking thymidine kinase (hsv-1 tk-) was resistant. linear competitive inhibition of purified hsv-1-induced thymidine kinase (tk) with thymidine as a variable substrate was observed for 9-(4-hydroxybutyl)guanine with an apparent ki value of ...19836312878
effect of aphidicolin on dna synthesis in hsv-1 infected and uninfected vero cells.the effect of aphidicolin on dna synthesis in herpes simplex virus type 1 (hsv-1) infected and uninfected vero cells was determined by isodensity banding of [32p]-labelled dna. a 50% inhibition of hsv-1 dna synthesis was observed at 0.07 microm aphidicolin while 2.1 and 1.3 microm were required to inhibit the cellular dna synthesis to 50% in infected and uninfected vero cells, respectively. when the viral dna synthesis was totally inhibited by 10 microm aphidicolin, the cellular dna synthesis wa ...19836312879
replication of herpes simplex virus in two cell systems derived from rhesus monkeys.the replication of herpes simplex virus (hsv) in two cell systems derived from rhesus monkeys (llc-mk2 and dbs-frhl-2) was studied. in llc-mk2, the growth of hsv-1 was abortive or extremely limited regardless of the multiplicity of infection, while that of hsv-2 was productive only on infection at high multiplicities. dbs-frhl-2 cells supported growth of both types of hsv, although growth was highly dependent on the age of monolayers and the infectious dose of virus inocula. plaques were produce ...19836312959
metabolism of 9-(1,3-dihydroxy-2-propoxymethyl)guanine, a new anti-herpes virus compound, in herpes simplex virus-infected cells.the metabolism of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (dhpg), one of the most promising new anti-herpes virus compounds, in hela cells infected with herpes simplex virus type 1 was compared with that in the uninfected hela cells. in the virus-infected cells, the uptake of dhpg was enhanced and the major metabolites were found to be the mono-, di-, and triphosphate derivatives. the formation of these metabolites was dependent on the extracellular concentration of dhpg (0.5 to 5.0 microm). vi ...19836313660
effect of sucrose phosphate and sorbitol on infectivity of enveloped viruses during storage.cytomegalovirus and varicella-zoster virus recovery from sucrose phosphate (0.2 m sp) and 70% sorbitol (sorbitol) was compared after storage at -70, 4, and 20 degrees c over time. recovery from 0.2 m sp was uniformly better. more tissue culture infective doses and infectious foci were recovered in cell monolayers inoculated with 0.2 m sp virus stocks as compared with viruses stored in 70% sorbitol. although both viruses were isolated from diluted fresh stocks (10(-1) through 10(-4], freezing dil ...19836313747
herpes simplex encephalitis. immunohistological demonstration of spread of virus via olfactory pathways in mice.six-week-old balb/c mice were inoculated intranasally with a suspension of hsv1 virus and the distribution of viral antigen in the brain 3-7 days later was surveyed using the immunoperoxidase technique. virus was first detectable in the brain 4 days later at 2 distinct sites: the trigeminal root entry zone in the brain stem and the olfactory bulbs. on succeeding days virus spread from the trigeminal focus to many other brain stem nuclei and, in some mice, to the thalamus and the cerebellum. from ...19836313868
high-resolution characterization of herpes simplex virus type 1 transcripts encoding alkaline exonuclease and a 50,000-dalton protein tentatively identified as a capsid protein.four partially overlapping mrnas (1.9, 2.3, 3.9, and 4.5 kilobases [kb]) were located between 0.16 and 0.19 map units on the herpes simplex virus type 1 genome. their direction of transcription was found to be from right to left. the 2.3-kb mrna was found to be early (beta), whereas the others were late (beta gamma). partial sequence analysis of the dna encoding these genes indicated that the promoter for the 2.3-kb mrna shares structural features with other early (beta) promoters. in vitro tran ...19836313961
the heterogenous regions in herpes simplex virus 1 dna.restriction endonuclease analyses of herpes simplex virus (hsv-1) dnas revealed variability in the electrophoretic migration of specific bam hi and kpn i fragments. the variable regions of the genome map at the ends and near the ends of both l and s components, near the l-s junction region and in middle of the s component. the variability of the fragments was demonstrated by comparing the electrophoretic mobility patterns of dnas from plaque-purified stocks originally derived from a common paren ...19836314098
dna sequence elements required for regulated expression of the hsv-1 glycoprotein d gene lie within 83 bp of the rna capsites.the genes of herpes simplex virus type 1 (hsv-1) are classified into three temporally regulated groups. the immediate-early (ie) genes are transcribed first by the pre-existing transcription apparatus of the cell. the early genes are transcribed only after ie-gene expression, and finally the late genes are activated. the control of transcription of the hsv-1 glycoprotein d (gd) gene (an early function) was studied by quantitative s1 mapping of rna produced in hsv-1 infected hela cells after shor ...19836314251
prophylactic and therapeutic treatment with acyclovir of genital herpes in the guinea pig.the antiviral drug, acyclovir, was tested on experimentally infected guinea pigs with either of two herpes simplex virus type 1 (hsv-1) isolates following intravaginal inoculation. the drug was continuously infused subcutaneously utilizing an osmotic pump. infusion was begun either prior to virus inoculation (prophylactic) or after virus inoculation at the time of first appearance of lesions (therapeutic). prophylactic treatment markedly reduced the severity of the genital lesions, the appearanc ...19836314343
[isolation and characteristics of a mutant herpes simplex virus type 1 resistant to phosphonoacetic acid].by successive passages and triple cloning of herpes simplex virus type 1 (hsv-1) in vero cell culture in the presence of increasing concentrations of phosphonoacetic acid (paa) a mutant of hsv-1 resistant to paa (paar) was derived and characterized. the resistance to the inhibitor was transmitted from paar-mutant to a sensitive strain (l2) by recombination performed by the marker rescue method using dna fragmented by hpa-1 restrictase. the resulting recombinant (r-551) was resistant to the inhib ...19836314671
[resistance of various herpes simplex virus strains to the action of chemical inhibitors].the effect of chemical inhibitors on reproduction of 2 laboratory and 3 vaccine strains of herpes simplex virus (hsv), types 1 and 2, was studied. by the time of the study the vaccine strains had undergone from 27 to 69 passages in chick embryo fibroblast cultures. all the vaccine strains (l2, us, and vn) exhibited 100-1000 fold higher resistance to phosphonoacetic acid than did the laboratory f+ and g strains, and the vaccine l2 strain (hsv-1) was also 1000-fold resistant to 1-beta-d-arabinofur ...19836314676
herpes simplex acyclovir-resistant mutant in experimental keratouveitis.acyclovir is a potent and selective antiviral agent. unfortunately, drug-resistant (acyclovir-resistant) mutants have already been reported in herpes simplex virus type 1 (hsv-1) orofacial infections. we have developed a laboratory acyclovir-resistant hsv-1 mutant. the natural course of acyclovir-resistant hsv-1 keratitis was found to be less virulent than that observed in wild type hsv-1 keratitis, but the rate of ganglionic latency was as high as that induced by the parental strain. in vitro s ...19836314952
a helix-destabilising protein from herpes simplex virus type i infected cells which specifically stimulates the virus induced dna polymerase activity in vitro.we have isolated a protein fraction from hsv-1 infected cells which binds specifically to single-stranded dna, facilitates a lowering of the melting temperature of poly[d(a-t)] and specifically stimulates the activity of the homologous virus-induced dna-dependent dna polymerase in vitro. these are major characteristics of a helix-destabilising protein, exemplified by the prokaryotic gene 32 protein.19836315006
dna sequence homology between two co-linear loci on the hsv genome which have different transforming abilities.a transcription unit at the herpes simplex virus (hsv) type 2 transforming region, mtr-2 (map coordinates 0.580-0.625), comprises two early, unspliced mrnas of 4.5 kb and 1.2 kb which are 3' co-terminal; a region including that specifying the 1.2-kb mrna has been sequenced. the putative translated portions of these two mrnas do not overlap and this feature, together with the arrangement of the mrnas, is similar to the apparently equivalent co-linear hsv-1 locus which however does not transform. ...19836315408
a vehicle for dna transfer and for recovery of transferred genes: lambda charon phage-pbr322 hybrid.recombinant charon 4a phages accommodating the herpes simplex virus (hsv-1) thymidine kinase (tk) gene, the ampicillin-resistance (apr) gene, and the replication origin of pbr322 were constructed. the phage dna was introduced into mouse ltk- cells by a free dna transfer method or phage-mediated dna transfer method [ishiura et al., mol. cell. biol. 2 (1982) 607]. analyses of the physical state of the transferred dna in the recipient cell genome showed that a dna fragment as long as 12.7 kb was in ...19836315539
a lambda library of herpes simplex virus type 1 (kos) dna fragments obtained by partial digestion with sau3a.large fragments of herpes simplex virus type 1 (hsv-1, strain kos) dna were produced by partial cleavage with sau3a and inserted into a phage lambda bamhi vector. recombinant phage (lambda kos) dna molecules were isolated and characterised. the final collection of phage recombinants contains partially overlapping inserts, which represent most of the hsv-1 genome. restriction enzyme analysis of many independent clones containing us sequences revealed sequence polymorphism in two specific regions.19836315542
inhibition of initiator-induced sv40 gene amplification in sv40-transformed chinese hamster cells by infection with a defective parvovirus.amplification of sv40 genes in sv40-transformed chinese hamster embryo cells (co631) by chemical carcinogens as well as by herpes simplex virus infection can be inhibited by infection with the defective parvovirus, aav-5. this is shown by in situ hybridization with sv40 dna of aav-5-infected co631 cells after treatment with herpes simplex virus type 1 or with chemical carcinogens: the initiator-induced selective amplification of sv40 sequences is prevented in the presence of the parvovirus. duri ...19836315605
elisa for the detection of herpes simplex virus antigens in the cerebrospinal fluid of patients with encephalitis.an inhibition enzyme-linked immunosorbent assay (elisa) for the detection of herpes simplex virus antigens in cerebrospinal fluid (csf) has been developed. a triton x-100 extract of herpes simplex virus type 1 (hsv-1) infected hep-2 cells was used to coat wells of polyvinyl chloride plates. rabbit anti-hsv-1 globulin served as the reference antibody and the csf specimens were tested at a final dilution of 1:4. positive results were obtained in csf specimens from 11/18 (61%) neonates with hsv inf ...19836315749
antigen-specific suppression of delayed type hypersensitivity to murine cytomegalovirus in mcmv-infected mice.when primary infection with murine cytomegalovirus (mcmv) was by the intravenous route, the resulting delayed type hypersensitivity (dth) to mcmv was reduced compared with subcutaneous or intraperitoneal infection. intravenous injection of 10(3) or more p.f.u. of mcmv also reduced the dth response to virus injected at the same time subcutaneously. when spleen cells from mice injected intravenously with mcmv 1 to 3 weeks earlier were transferred to subcutaneously infected mice, the resulting dth ...19836315864
herpes simplex virus defective genomes: structure of hsv-1 ang defective dna of class ii and encoded polypeptides.sequence organization and origin of hsv-1 strain angelotti (ang) class ii defective dna (hsv-1 ang ddna1) were examined in detail by establishing physical maps and by molecular cloning. ddna1 consists of concatemers of tandem repeat units in which sequences from the ul region spanning map coordinates 0.37 to 0.415 of standard hsv ang dna are covalently linked to trs/irs sequences. the size of the repeat unit was determined to be about 8.9 kilobase pairs (kb), comprising sequences of 7.3 kb from ...19836315866
accumulation of herpes simplex virus type 1 glycoprotein d in adhesion areas of infected cells.by indirect immunofluorescence microscopy (iif) we have localized glycoprotein d (gd) of herpes simplex virus-infected cells to the vinculin-containing junctional areas and to the focal adhesion sites on the ventral surface of the cells. double-staining iif showed that gd and vinculin co-distributed in the infected cells and treatment of the infected cells 4 h post-infection with rabbit antibodies to gd prevented attachment of the cells to the growth substratum. our results therefore support the ...19836315867
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