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conservative mutations of glutamine-125 in herpes simplex virus type 1 thymidine kinase result in a ganciclovir kinase with minimal deoxypyrimidine kinase activities.the herpes simplex virus type 1 thymidine kinase (hsv-1 tk) is the major anti-herpes virus pharmacological target, and it is being utilized in combination with the prodrug ganciclovir as a toxin gene therapeutic for cancer. one active-site amino acid, glutamine-125 (gln-125), has been shown to form hydrogen bonds with bound thymidine, thymidylate, and ganciclovir in multiple x-ray crystal structures. to examine the role of gln-125 in hsv-1 tk activity, three site-specific mutations of this resid ...200010747801
polyherbal formulations with wide spectrum antimicrobial activity against reproductive tract infections and sexually transmitted pathogens.recent reports indicate high incidence of genital infections, most of which are sexually transmitted. although specific drugs and antibiotics are available for some, a safe spermicidal formulation with wide spectrum antimicrobial action would be a desirable addition to the presently available spermicides.200010735590
identification and initial characterization of four novel members of the interleukin-1 family.interleukin-1 (il-1), fibroblast growth factors (fgfs), and their homologues are secreted factors that share a common beta-barrel structure and act on target cells by binding to cell surface receptors with immunoglobulin-like folds in their extracellular domain. while numerous members of the fgf family have been discovered, the il-1 family has remained small and outnumbered by il-1 receptor homologues. from expressed sequence tag data base searches, we have now identified four additional il-1 ho ...200010744718
herpes simplex virus virion host shutoff (vhs) activity alters periocular disease in mice.during lytic infection, the virion host shutoff (vhs) protein of herpes simplex virus (hsv) mediates the rapid degradation of rna and shutoff of host protein synthesis. in mice, hsv type 1 (hsv-1) mutants lacking vhs activity are profoundly attenuated. hsv-2 has significantly higher vhs activity than hsv-1, eliciting a faster and more complete shutoff. to examine further the role of vhs activity in pathogenesis, we generated an intertypic recombinant virus (kosv2) in which the vhs open reading f ...200010729135
cross-reactive antibodies against gm2 and cmv-infected fibroblasts in guillain-barré syndrome.to investigate whether anti-gm2 antibodies in patients with guillain-barré syndrome (gbs) are induced by molecular mimicry with cytomegalovirus (cmv).200010751257
conditionally replicating herpes vectors for cancer therapy. 200010749560
rapid detection of glycoprotein g gene for the diagnosis and typing of herpes simplex virus infection in genital herpes.to develop a new, rapid, and convenient technique for the diagnosis and typing of herpes simplex virus (hsv) in genital herpes (gh).199910754943
detection of herpes simplex virus dna in maternal breast milk by in situ hybridization with tyramide signal amplification.in this study we investigated the prevalence of herpes simplex virus 1 (hsv-1) and 2 (hsv-2) in maternal breast milk using the technique of in situ hybridization combined with the sensitive detection system of tyramide signal amplification. breast milk samples were collected from both breasts of 34 puerperals 4-5 days after delivery. hsv dna was detected in 16 out of 34 examined breast milk specimens. hsv dna was found in the milk of both breasts in 10 cases (62.5%), in that of left breast in 4 ...199910757038
synthesis of (z)- and (e)-9-[(2-hydroxyethylidene)cyclopropyl]adenine--new methylenecyclopropane analogues of adenosine and their substrate activity for adenosine deaminase.synthesis of z- and e-methylenecyclopropane analogues of adenosine 3 and 4 by alkylation of adenine with novel alkylating agent 5 is described. the e-isomer 4 is a substrate for adenosine deaminase. compounds 3 and 4 were tested for antiviral activity against hcmv, hsv-1, hsv-2, ebv, vzv, hbv and hiv-1.200010772701
synthesis and antiviral activities of enantiomeric 1-[2-(hydroxymethyl) cyclopropyl] methyl nucleosides.cyclopropyl carbocyclic nucleosides have been synthesized from the key intermediate 2 which was converted to the mesylated cyclopropyl methyl alcohol 3. condensation of compound 3 with various purine and pyrimidine bases gave the desired nucleosides. all synthesized nucleosides were evaluated for antiviral activity and cellular toxicity. among them adenine 22 and guanine 23 derivatives showed moderate antiviral activity against hiv-1 and hbv. none of the other compounds showed any significant an ...200010772713
efficacy of topical acyclovir monophosphate, acyclovir, or penciclovir in orofacial hsv-1 infections of mice and genital hsv-2 infections of guinea pigs.the purpose of these studies was to compare the efficacy of acyclovir monophosphate (acvmp), acyclovir (acv), or penciclovir (pcv) against hsv-1 in an orofacial infection of mice and against acv sensitive and resistant genital hsv-2 infections of guinea pigs. treatment was initiated 24, 48, or 72 hours post inoculation with 5% acvmp, 5% acv (zovirax) or 1% pcv (denavir). in all experiments, similar efficacy was obtained for acvmp and acv, whereas pcv was considerably less effective.200010772730
use of herpes simplex virus (hsv) type 1 iscoms 703 vaccine for prophylactic and therapeutic treatment of primary and recurrent hsv-2 infection in guinea pigs.the effect of subunit vaccination on the incidence and severity of primary and recurrent genital herpes was investigated in the female guinea pig model of herpes simplex virus (hsv) type 2 genital infection. after prophylactic immunization with zwitterionic detergent-solubilized hsv-1 glycoproteins formulated with alhydrogel or as immunostimulating complex particles, significant reductions in the incidence and severity of primary herpetic illness were observed in both vaccinated groups compared ...200010762560
neonatal herpes simplex virus type 1 brain infection affects the development of sensorimotor gating in rats.the effect of neonatal brain infection of herpes simplex virus type 1 (hsv-1) on the development of sensorimotor function in the rat was investigated using an acoustic startle paradigm. intracerebral inoculation of hsv-1 at day 2 after birth, but not at day 4, caused a significant delay in the development of prepulse inhibition of acoustic startle. a decrease in prepulse inhibition was shown at 37, 46 and 58 days of age in these rats compared to control rats. no evidence was obtained for other b ...200010773211
herpes simplex virus 1 (hsv-1) strain hszp glycoprotein b gene: comparison of mutations among strains differing in virulence.the nonpathogenic hszp strain of hsv-1 induces large polykaryocytes due to a syn3 mutation (his for arg at residue 858) in the c-terminal endodomain of glycoprotein b (gb) (40). we determined the nucleotide (nt) sequence of the ul27 gene specifying the gb polypeptide of hszp (gbhszp) and found 3 mutations in its ectodomain at aminoacids (aa) 59, 79 and 108. the angpath virus, which also has a syn3 mutation in the c-terminal endodomain of gb (val for ala at residue 855) is pathogenic for adult mi ...200010766304
virus isolation study of the human ganglion geniculi (nerve vii). 199410774427
the role of natural killer cells in protection of mice against death and corneal scarring following ocular hsv-1 infection.c57bl/6 mice depleted of nk (natural killer) cells with anti-asialo-gm1 antibody were more susceptible to lethal hsv-1 ocular challenge (12% survival) than control c57bl/6 mice (100% survival), cd4+ depleted mice (100% survival), cd8+ depleted mice (80% survival), or macrophage depleted mice (85% survival). nk depletion also resulted in significantly higher levels of hsv-1 induced corneal scarring than was seen with any of the other groups. c57bl/6 mice depleted of nk cells with pk136 (anti-nk1. ...200010774588
the exchange of cognate tata boxes results in a corresponding change in the strength of two hsv-1 early promoters.previous analysis of two herpes simplex virus type-1 (hsv-1) promoters controlling expression of mrna encoding early genes (u(l)37 and u(l)50) showed that the u(l)50 (dutpase) promoter is at least 6-fold stronger both in its normal genomic location and in the non-essential gc locus. in the present report we demonstrate that the tata element of either promoter is the major determinant of promoter strength. when the u(l)37 tata element (cgtataac) was mutated with two base changes to the u(l)50 tat ...200010766301
[molecular epidemiology of human alpha-herpesvirus infection].herpes simplex virus type 1, 2 (hsv-1, 2) and varicella-zoster virus(vzv) are significant pathogens in humans. these three viruses belong to the alpha-herpesvirus subfamily. the molecular epidemiological analyses of the viruses are based on the heterogeneity of each viral genome found in isolates. hsv-1, 2 strains are classified into genotypes as intratypic variations by gains or losses of cleavage sites using restriction endonucleases recognizing 6-base pairs. on the other hand, vzv strains can ...200010774203
herpes simplex virus 1 late gene expression is preferentially inhibited during infection of the taf250 mutant ts13 cell line.a key component of the polymerase ii transcription machinery is the transcription factor tfiid, a complex that contains the tata-box binding protein and several (10-12) associated factors designated as tafs (tbp-associated factors). ts13 cells, which contain a temperature-sensitive mutant in taf250, the largest subunit of tfiid, exhibit promoter-specific defects in gene expression at the nonpermissive temperature, suggesting that individual tafs are required for transcription of specific subsets ...200010772991
seeing the herpesvirus capsid at 8.5 a.human herpesviruses are large and structurally complex viruses that cause a variety of diseases. the three-dimensional structure of the herpesvirus capsid has been determined at 8.5 angstrom resolution by electron cryomicroscopy. more than 30 putative alpha helices were identified in the four proteins that make up the 0.2 billion-dalton shell. some of these helices are located at domains that undergo conformational changes during capsid assembly and dna packaging. the unique spatial arrangement ...200010797014
molecular epidemiology of herpes simplex virus type 1 genital infection in association with clinical manifestations.the antigenic types of herpes simplex virus (hsv), hsv-1 and hsv-2 are considered to be the etiology of genital herpes. symptoms of primary hsv-1 and hsv-2 genital infections are similar, however, recurrence of the infection is less frequent after the hsv-1-related genital infection. we determined genotypes of 79 hsv-1 strains isolated from genital lesions in women (43 from primary and 36 from recurrent infections), by analyzing restriction fragment length polymorphism of the hsv-1 strains. each ...200010795518
specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene.to produce disease, viruses must enter the host, multiply locally in host tissues, spread from the site of entry, and overcome or evade host immune responses. at each stage in this infectious process, specific microbial and host genes determine the ultimate virulence of the virus. genetic approaches have identified many viral genes that play critical roles in virulence and are presumed to target specific components of the host innate and acquired immune response. however, formal proof that a vir ...200010801979
synthesis of 4'-substituted nucleosides and their biological evaluation.4'-c-ethynyl-beta-d-arabino- and 4'-c-ethynyl-beta-d-2'-deoxy-ribo-pentofuranosyl pyrimidines were synthesized. most of these 4'-ethynyl nucleosides showed interesting biological activities.199910780412
spiropentane mimics of nucleosides: analogues of 2'-deoxyadenosine and 2'-deoxyguanosine. synthesis of all stereoisomers, isomeric assignment, and biological activity.synthesis of spirocyclic analogues of 2'-deoxyadenosine and 2'-deoxyguanosine (12a-15a and 12b-15b) is described. rhodium-catalyzed reaction of ethyl diazoacetate with methylenecyclopropane 19, obtained from 2-bromo-2-bromomethylcyclopropane 17 via debromination (16), reduction (18), and acetylation (19), gave a mixture of all four isomeric spiropentanes 20a-20d. hydrolysis afforded hydroxy carboxylic acids 21a-21d. acetylation of separated proximal + medial-syn isomers 21a + 21b and medial anti ...200010814087
difference in incidence of spontaneous mutations between herpes simplex virus types 1 and 2.spontaneous mutations within the herpes simplex virus (hsv) genome are introduced by errors during dna replication. indicative of the inherent mutation rate of hsv dna replication, heterogeneous hsv populations containing both acyclovir (acv)-resistant and acv-sensitive viruses occur naturally in both clinical isolates and laboratory stocks. wild-type, laboratory-adapted hsv type 1 (hsv-1) strains kos and cl101 reportedly accumulate spontaneous acv-resistant mutations at a frequency of approxima ...200010817703
etiology of microglial nodules in brains of patients with acquired immunodeficiency syndrome.microglial nodules associated with opportunistic and hiv-related lesions are frequently found in the brains of aids patients. however, in many cases, the causative agent is only presumptively suspected. we reviewed 199 brains of aids patients with micronodular lesions to clarify their etiology by immunohistochemistry (to toxoplasma gondii, cytomegalovirus, herpes simplex virus i/ii, varicella zoster virus and hiv-p24 core protein), pcr (for herpetic viruses and mycobacterium tuberculosis) and el ...200010786996
expression of ryanodine receptor ryr3 produces ca2+ sparks in dyspedic myotubes.discrete, localized elevations of myoplasmic [ca2+], ca2+ 'sparks', were readily detected using the fluorescent ca2+ indicator fluo-3 and laser scanning confocal microscopy in 'dyspedic' 1b5 myotubes, i.e. myotubes which do not express ryanodine receptors (ryrs), transduced with virions containing cdna for ryr type 3 that were saponin permeabilized to allow dye entry. ca2+ sparks were never observed in non-transduced ryr null myotubes. the spatial locations of sparks observed in permeabilized my ...200010811728
unwinding of a herpes simplex virus type 1 origin of replication (ori(s)) by a complex of the viral origin binding protein and the single-stranded dna binding protein.a herpes simplex virus type 1 (hsv-1) ori(s) analogue in which the a+t sequence linking the box i and ii elements was replaced by two single-stranded oligo(dt)s is unwound by the ul9 protein-icp8 complex. unwinding of wild-type ori(s) by the ul9 protein-icp8 complex was also observed under conditions which destabilize the a+t sequence. these experiments support a model for the unwinding of ori(s) in which destabilization of the a+t sequence can generate a single-stranded dna binding site for icp ...200010823882
intravitreal toxicology and duration of efficacy of a novel antiviral lipid prodrug of ganciclovir in liposome formulation.to evaluate the intraocular safety and antiviral treatment efficacy of the sustained lipid prodrug of ganciclovir, 1-o-hexadecylpropanediol-3-phospho-ganciclovir (hdp-p-gcv), as an intravitreal injectable drug system for viral retinitis.200010798672
fibril formation and neurotoxicity by a herpes simplex virus glycoprotein b fragment with homology to the alzheimer's a beta peptide.despite significant progress in the elucidation of the genetic basis of early-onset familial alzheimer's disease (ad), the etiology of sporadic cases remains elusive. although certain genetic loci play a role in conferring susceptibility in some sporadic ad cases, it is likely that the etiology is multifactorial; hence, the majority of cases cannot be attributed to genetic factors alone, indicating that environmental factors may modulate the onset and/or progression of the disease. head injury a ...200010821670
tumor-selective gene transduction and cell killing with an oncotropic autonomous parvovirus-based vector.a recombinant mvmp of the fibrotropic strain of minute virus of mice (mvmp) expressing the chloramphenicol acetyltransferase reporter gene was used to infect a series of biologically relevant cultured cells, normal or tumor-derived, including normal melanocytes versus melanoma cells, normal mammary epithelial cells versus breast adenocarcinoma cells, and normal neurons or astrocytes versus glioma cells. as a reference cell system we used normal human fibroblasts versus the sv40-transformed fibro ...200010822306
monoclonal antibodies suitable for type-specific identification of herpes simplex viruses by a rapid culture assay.eight monoclonal antibodies (mabs) to herpes simplex viruses 1 and/or 2 (hsv-1, hsv-2) were tested for their reactivity with 190 previously typed hsv-positive clinical specimens in order to determine their suitability for use as type-specific reagents. using a rapid culture assay we found that two mabs (t51 and t96) identified hsv-1 in all the 94 specimens, previously found hsv-1-positive, but did not react with the 96 specimens, previously found hsv-2-positive. in contrast, one mab (303) confir ...199910825932
enhanced green fluorescent protein fusion proteins of herpes simplex virus type 1 thymidine kinase and cytochrome p450 4b1: applications for prodrug-activating gene therapy.to monitor therapeutic transgene expression, we developed fusion genes of enhanced green fluorescent protein (egfp) with two different prodrug-activating enzyme genes: herpes simplex virus type 1 thymidine kinase (hsv-tk) and rabbit cytochrome p450 4b1 (cyp4b1). expression of the resulting fusion proteins, tk-egfp and 4b1-egfp, rendered transduced human and rodent glioma cells sensitive to cytotoxic treatment with the corresponding prodrugs ganciclovir and 4-ipomeanol. ganciclovir and 4-ipomeano ...200010830728
herpes simplex virus: the importance of asymptomatic shedding.herpes simplex virus (hsv) is frequently shed after infection of the genital or perianal area. hsv shedding, as determined by culture, occurs on about 3% of days for immunocompetent women and men, and more for persons with hiv infection or if measured by polymerase chain reaction (pcr). most horizontal and vertical transmission of hsv occurs during unrecognized or asymptomatic shedding, and the majority of hsv-2-infected persons are unaware of their infection. many persons with 'asymptomatic' hs ...200010855766
plasmid dna encoding ifn-alpha 1 antagonizes herpes simplex virus type 1 ocular infection through cd4+ and cd8+ t lymphocytes.the present study was undertaken to further characterize the anti-viral efficacy of a plasmid dna encoding ifn-alpha1 against ocular herpes simplex virus type 1 (hsv-1) infection. in mice ocularly treated with plasmid dna encoding ifn-alpha 1, the efficacy of the transgene was inversely proportional to the amount of virus used to infect the mice. ocular treatment of mice with the ifn-alpha 1 transgene was the only mucosal route tested that showed efficacy against ocular hsv-1 infection compared ...200010843699
immunomodulatory therapy in the management of viral infections in patients with hiv infection.human immunodeficiency virus (hiv) causes disease by infecting lymphocytes and progressively destroying critical regulatory and effector cells of the immune system, leaving patients vulnerable to a number of bacterial, fungal, and viral infections. facial herpes (herpes simplex virus-1 [hsv-1]), genital herpes (hsv-2), herpes zoster (varicella zoster virus), oral hairy leukoplakia (epstein-barr virus), kaposi's sarcoma (hhv-8), molluscum contagiosum, condyloma acuminata (human papillomavirus [hp ...200010861104
testing for type-specific antibody to herpes simplex virus--implications for clinical practice.recently, assays that can distinguish between antibody to herpes simplex virus (hsv) types 1 and 2 have become available. these tests not only make it possible to better define infection in symptomatic patients and their sexual partners but also to identify asymptomatic infected individuals who may, nevertheless, be infectious. type-specific antibody tests for hsv have several potential applications. they have a clear role in helping to define the worldwide distribution and pattern of hsv infect ...200010855767
the mal proteolipid is necessary for the overall apical delivery of membrane proteins in the polarized epithelial madin-darby canine kidney and fischer rat thyroid cell lines.the mal proteolipid has been recently demonstrated as being necessary for correct apical sorting of the transmembrane influenza virus hemagglutinin (ha) in madin-darby canine kidney (mdck) cells. the fact that, in contrast to mdck cells, fischer rat thyroid (frt) cells target the majority of glycosylphosphatidylinositol (gpi)-anchored proteins to the basolateral membrane provides us with the opportunity to determine the role of mal in apical transport of membrane proteins under conditions in whi ...200010848627
clinical management of selected oral fungal and viral infections during hiv-disease.the purpose of this review is to describe current possibilities of management of selected fungal and viral oral opportunistic infections including oral candidiasis, herpes simplex type 1 and 2-related lesions (hsv1,2), oral hairy leukoplakia (ohl) and oral lesions associated with human papilloma viruses (hpv). less common diseases such as cytomegalovirus infection or human herpes virus type 8 associated with kaposi's sarcoma and others are not considered. in a number of instances lifelong therap ...199910858761
role of serology in the diagnosis of herpes simplex encephalitis.twenty one cerebrospinal fluid (csf)/brain tissue (16 csf and 5 brain tissue) from patients clinically suspected of herpes simplex encephalitis (hse) were collected during one year period and was subjected for the detection of hsv type i and type ii antigen by direct immunofluorescence (dif). paired serum and csf samples obtained from 12 patients were tested for herpes simplex virus antibodies by indirect immunofluorescence test. of the 21 cases, two were positive for hsv-1 antigen in csf and on ...199910862294
transfusion-associated infections with cytomegalovirus and other human herpesviruses.of all human herpesviruses, human cytomegalovirus (hcmv) is the most significant cause of transfusion-associated (ta) morbidity and mortality. the problem of ta hcmv infection differs from that of other transfusion-transmitted infections in that only certain groups of patients require hcmv-free blood or blood components, i.e. seronegative pregnant women, premature infants of low birth weight who are born to seronegative mothers, seronegative recipients of allogeneic bone marrow transplants from ...200010878482
[studies on the antiviral activity of silver sulfathiazole].silver sulfathiazole shows strong antibacterial activity and good tolerance after topical application. the aim of the study was to determine the antiviral activity of silver sulfathiazole in tissue culture after incubation of drug and virus. the antiviral activity was measured after various periods of exposure and at different drug concentrations. the results obtained indicate the activity of silver sulfathiazole against herpesvirus type 1 and type 2. this drug suppresses or completely inactivat ...199910865442
two leaky-late hsv-1 promoters differ significantly in structural architecture.the hsv-1 vp5 and vp16 transcripts are expressed with leaky-late (gamma1) kinetics and reach maximal levels after viral dna replication. while the minimal vp5 promoter includes only an sp1 site at -48, a tata box at -30, and an initiator (inr) element at the cap site, here we show that elements upstream of -48 can functionally compensate for the mutational loss of the critical sp1 site at -48. to determine whether this is a general feature of leaky-late promoters, we have carried out a detailed ...200010873762
purification and characterization of of-1, a host factor implicated in herpes simplex replication.a human cellular factor (of-1) has been previously implicated in replication of herpes simplex virus, type 1. this protein binds to three conserved regions (boxes i, ii, and iii) in the viral replication origin and appears to be required for viral dna synthesis (dabrowski, c. c., carmillo, p. j., and schaffer, p. a. (1994) mol. cell. biol. 14, 2545-2555). in the present study, we have partially purified and characterized of-1 from human cells. this protein appears to consist of a tetramer compos ...200010878004
transduction of human pancreatic tumor cells with vesicular stomatitis virus g-pseudotyped retroviral vectors containing a herpes simplex virus thymidine kinase mutant gene enhances bystander effects and sensitivity to ganciclovir.we examined the suitability of moloney murine leukemia virus (mlv) 4070a-, cat endogenous virus (cev) rd114-, or vesicular stomatitis virus g (vsv-g)-pseudotyped retroviruses containing the humanized enhanced green fluorescent protein (hegfp) or one of two herpes simplex virus thymidine kinase (hsv-tk) genes to transduce and provide gene expression in human pancreatic tumor cells. fluorescence-activated cell sorter analysis demonstrated that vsv-g-pseudotyped hegfp vector infected a greater perc ...200010880025
design, synthesis, and biological evaluation of tricyclic nucleosides (dimensional probes) as analogues of certain antiviral polyhalogenated benzimidazole ribonucleosides.the polyhalogenated benzimidazole nucleosides 2,5, 6-trichloro-1-(beta-d-ribofuranosyl)benzimidazole (tcrb) and the 2-bromo analogue (bdcrb) were synthesized in our laboratory and established as potent and selective inhibitors of human cytomegalovirus (hcmv) with a novel mode of action. in an effort to study the behavior of the key substructure in a dimensionally extended manner and probe the spatial limitation of the target enzyme(s), a series of 2-substituted 6, 7-dichloro-1-(beta-d-ribofurano ...200010882370
6-n-acyltriciribine analogues: structure-activity relationship between acyl carbon chain length and activity against hiv-1.triciribine (tcn) and triciribine-5'-monophosphate (tcn-p) are active against hiv-1 at submicromolar concentrations. in an effort to improve and better understand this activity, we have conducted a structure-activity relationship study to explore the tolerance of tcn to structural modifications at the 6-position. a number of 6-n-acyltriciribine analogues were synthesized and evaluated for antiviral activity and cytotoxicity. the cytotoxicity of these compounds was minimal in three human cell lin ...200010882373
mature dendritic cells infected with herpes simplex virus type 1 exhibit inhibited t-cell stimulatory capacity.mature dendritic cells (dc) are the most potent antigen-presenting cells within the entire immune system. interference with the function of these cells therefore constitutes a very powerful mechanism for viruses to escape immune responses. several members of the herpesviridae family have provided examples of such escape strategies, including interference with antigen presentation and production of homologous cytokines. in this study we investigated the infection of mature dc with herpes simplex ...200010888653
a prospective study of cytomegalovirus, herpes simplex virus 1, and coronary heart disease: the atherosclerosis risk in communities (aric) study.conflicting evidence exists implicating infectious disease in the pathological processes leading to coronary heart disease (chd). the objective of this article is to describe the relationship of previous infection with cytomegalovirus (cmv) and herpes simplex virus 1 to incident chd in a population-based cohort study.200010888976
percutaneous gene therapy using recombinant adenoviruses encoding human herpes simplex virus thymidine kinase, human pai-1, and human nos3 in balloon-injured porcine coronary arteries.local intracoronary delivery of recombinant adenoviruses expressing anti-migratory or anti-proliferative proteins including human constitutive endothelial nitric oxide synthase (nos3), plasminogen activator inhibitor 1 (pai-1), or herpesvirus thymidine kinase (tk) (combined with ganciclovir) was used to prevent neointimal formation in porcine coronary arteries. after balloon injury of the left anterior descending (lad) coronary artery, animals received an intramural injection of adenovirus (1.5 ...200010890742
synthesis and antiviral activity of 3-(beta-d-ribofuranosyl)-1,2,4-oxadiazole-5-carboxamide.3-(beta-d-ribofuranosyl)-1,2,4-oxadiazole-5-carboxamide (5) was prepared by condensation reaction of amidoxime 6 with monoethyl oxaloyl chloride followed by reaction with ammonia. the compound 5, however, did not exhibit any significant activity against herpes simplex virus type-i (hsv-i) and semliki forest virus (sfv).200010893705
assessment trials of the therapeutic efficacy of the drug "zovirax" in some recurrent ocular and genital herpetic infections.in this work are reported the results of the researches performed by the authors more than a decade ago, aimed at assessing the clinical benefit of the introduction of the drug "zovirax" in the treatment of recurrent herpetic infections with genital or ocular location. the results of the treatment carried out on a restricted group of patients were positive both in cases of genital herpes and of herpetic keratitis. the clinical benefit consisted in the reduction of the mean duration of the diseas ...199810892424
observations regarding the neurocytokaryological study of the experimental infection with herpes simplex virus type 1 and type 2 in the white mouse.mice distributed in groups were inoculated with the herpes virus simplex type 1 and type 2 strains in various dilutions (10(-1)-10(-7)), which had been maintained on primary human embryo cell cultures. the animals were killed and homogenates were prepared of their brains, which were used for testing the infective titre in vivo and for the isolation of nuclei, by means of the hymer-kuff technique. for the cytokaryological examinations, smears were prepared from the homogenate, which were stained ...199810892432
treatment with meliacine, a plant derived antiviral, prevents the development of herpetic stromal keratitis in mice.herpetic stromal keratitis is caused by ocular infection with herpes simplex virus type 1 (hsv-1) and constitutes a leading cause of human blindness. the effect of meliacine, an antiviral compound isolated from leaves of melia azedarach l. that inhibits hsv-1 replication in vitro, was examined on experimental corneal hsv-1 inoculation in balb/c mice. mice were inoculated with hsv-1 strain kos at their corneas after abrasion. meliacine was administered topically 3 times a day for 4 days beginning ...200010897066
the catalytic subunit of herpes simplex virus type 1 dna polymerase contains a nuclear localization signal in the ul42-binding region.the herpes simplex virus type 1 dna polymerase consists of a catalytic subunit (pol or ul30) and a processivity factor (ul42). the pol/ul42 interaction, which occurs through the extreme c-terminus of pol, is essential for hsv-1 replication and thus represents a valid target for drug inhibition. we recently showed (a. loregian et al. (1999) proc. natl. acad. sci. usa 96, 5221-5226) that an oligopeptide corresponding to the 27 c-terminal amino acids of pol, when delivered into herpes simplex virus ...200010891416
evaluation of tta-mediated gene activation system on human cytomegalovirus and herpes simplex virus type-1 infections.the tetracycline-controlled transactivator (tta)-mediated gene activation system was examined in virus infected cells to determine its role in the control of gene expression. in the presence of tta, the gene expression from the teto-modified minimal promoter was efficiently activated in the uninfected cells, whereas essentially no activation was observed from the only minimal promoter without the seven direct repeats of 42 bp teto sequences. however, essentially no activation was observed when o ...200010896059
neutral sphingomyelinase-inhibiting guanidines prevent herpes simplex virus-1 replication.we synthesized a series of new guanidinium derivatives and studied the inhibitory activity on both neutral sphingomyelinase and herpes simplex virus-1 (hsv-1) replication. the lipophilic quality of the molecules was found to be correlated with the inhibitory potential of the compounds. undecylidene-aminoguanidine was superior to derivatives with 10, 8 or 6 carbon atoms whereas propylidene-aminoguanidine was completely inactive. decylidene-aminoguanidine was the most active derivative, with 10 ca ...200010894556
association between clinical disease activity and epstein-barr virus reactivation in ms.to assess the potential significance of epstein-barr virus (ebv) reactivation in disease activity in ms patients.200010908887
conformational lability of herpesvirus protein vp22.the herpesvirus protein vp22 traffics between cells, being exported from expressing cells in a non-golgi-dependent manner and localizing in the nuclei of surrounding cells. this transport is retained in certain vp22 fusion proteins, making vp22 a candidate for use in macromolecular drug delivery. in an effort to understand the physical basis for this activity, we have initiated structural studies of vp22.c1, the c-terminal half of vp22, which possesses the full transport activity of the native p ...200010913125
molecular localisation of a g-protein mrna using differential display and in situ hybridization.defining molecular repertoires within virally infected tissues of the nervous system may provide insight into the pathogenesis of, and immunity to, neurotropic viruses. here we report the application of such a method, namely mrna differential display (dd), to the identification of mrnas that are expressed at different levels in herpes simplex virus (hsv) infected nervous tissue from immunocompetent and cd8(+) lymphocyte depleted mice. small amounts of input rna can be used by dd, making the meth ...200010906495
hsv-1 amplicon vectors--simplicity and versatility. 200010899823
the conserved carboxyl-terminal half of herpes simplex virus type 1 regulatory protein icp27 is dispensable for viral growth in the presence of compensatory mutations.icp27 is an essential herpes simplex virus type 1 (hsv-1) immediate-early protein that regulates viral gene expression by poorly characterized mechanisms. previous data suggest that its carboxyl (c)-terminal portion is absolutely required for productive viral infection. in this study, we isolated m16r, a second-site revertant of a viral icp27 c-terminal mutant. m16r harbors an intragenic reversion, as demonstrated by the fact that its cloned icp27 allele can complement the growth of an hsv-1 icp ...200010906189
therapy of head and neck squamous cell carcinoma with an oncolytic adenovirus expressing hsv-tk.currently available therapeutic modalities for advanced head and neck squamous cell carcinoma (hnscc), such as radical surgery, high-dose radiotherapy, and chemotherapy, are of limited efficacy. overall survival has not significantly improved over the past 30 years; thus, hnscc represents a promising target for new therapeutic approaches, such as gene therapy. a major obstacle to the development of effective suicide gene therapy strategies that rely on in situ transduction of tumor cells is the ...200010933912
hsv-1-based vectors for gene therapy of neurological diseases and brain tumors: part ii. vector systems and applications.many properties of hsv-1 are especially suitable for using this virus as a vector to treat diseases affecting the central nervous system (cns), such as parkinson's disease or malignant gliomas. these advantageous properties include natural neurotropism, high transduction efficiency, large transgene capacity, and the ability of entering a latent state in neurons. selective oncolysis in combination with modulation of the immune response mediated by replication-conditional hsv-1 vectors appears to ...199910933055
qsar and molecular graphics analysis of n2-phenylguanines as inhibitors of herpes simplex virus thymidine kinases.a quantitative structure-activity relationship study of n2-(substituted)-phenylguanines (phg) as inhibitors of herpes simplex virus thymidine kinase (hsv tk) was performed. the activity of a set of phg derivatives were analyzed against the thymidine kinase of herpes simplex virus types 1 (hsv1 tk) and 2 (hsv2 tk). classic and calculated physicochemical parameters were included in the analysis. the results showed that there is an important difference in the activity of the meta substituted phg de ...200010935205
herpes simplex virus-specific t cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive t cells.herpetic stromal keratitis (hsk) is a t-cell-mediated inflammatory disease initiated by a herpes simplex virus (hsv) infection of the cornea. recently, studies in the hsk mouse model have shown that the immunopathogenic t cells are directed against the hsv protein ul6 cross-reacting with an unknown corneal autoantigen. whether this type of autoimmunity plays a role in human hsk was analyzed.200010937573
characterization by two-dimensional gel electrophoresis of host proteins whose synthesis is sustained or stimulated during the course of herpes simplex virus type 1 infection.herpes simplex virus type 1 (hsv-1) gene expression is concomitant with a selective shutoff of host protein synthesis. while the synthesis of the vast majority of cellular proteins is inhibited immediately after infection, several cellular proteins continue to be synthesized, even during the late phase of infection. because these cellular proteins may intervene in the life cycle of the virus, we undertook two-dimensional polyacrylamide gel electrophoresis (2-d page) analyses to evaluate the prop ...200010939467
imaging transgene expression with radionuclide imaging technologies.a variety of imaging technologies are being investigated as tools for studying gene expression in living subjects. noninvasive, repetitive and quantitative imaging of gene expression will help both to facilitate human gene therapy trials and to allow for the study of animal models of molecular and cellular therapy. radionuclide approaches using single photon emission computed tomography (spect) and positron emission tomography (pet) are the most mature of the current imaging technologies and off ...200010933072
expression of intracellular ifn-gamma in hsv-1-specific cd8+ t cells identifies distinct responding subpopulations during the primary response to infection.cutaneous infection in the footpads of c57bl/6 mice with hsv-1 results in an accumulation of activated (cd44high cd25+) cd8+ t cells within the draining popliteal lymph node (pln). these studies were undertaken to evaluate the frequency and phenotype of the cd8+ t cell population within the pln, recognizing the single immunodominant hsv-1 epitope derived from the viral envelope glycoprotein, glycoprotein b (gb), using an intracellular ifn-gamma-staining assay. it revealed that approximately 6% o ...200010925295
the role of the e1b 55 kda gene product in oncolytic adenoviral vectors expressing herpes simplex virus-tk: assessment of antitumor efficacy and toxicity.in this study, we evaluated three herpes simplex virus-1 thymidine kinase (hsv-tk) carrying replication-competent adenoviral vectors with and without the ad5 e1b 55 kda gene to assess whether this gene product has an influence on their antitumor efficacy, replication kinetics, and potential hepatotoxicity. furthermore, we assessed the efficacy of these vectors in combination with ganciclovir (gcv). when compared with wild-type adenovirus, the recombinant vectors, in particular the e1b 55 kda-del ...200010945625
synthesis and biological evaluation of certain alpha,beta-unsaturated ketones and their corresponding fused pyridines as antiviral and cytotoxic agents.a new series of 3,5-bis(arylidene)-4-piperidones, as chalcone analogues carrying variety of aryl and heteroaryl groups, pyrazolo[4,3-c]pyridines, pyridolo[4,3-c]pyrimidines, and pyrido[4,3-c]-pyridines, carrying an arylidene moiety, and a series of pyrano[3,2-c]pyridines, as flavone and coumarin isosteres, were synthesized and screened for their in vitro antiviral and antitumor activities at the national cancer institute (nci). compounds 9 and 18 proved to be active against herpes simplex virus- ...200010956199
antibody-dependent enhancement of hsv-1 infection by anti-gk sera.we previously reported that vaccination of balb/c mice with the baculovirus expressed hsv-1 glycoprotein k (gk) or passive transfer of gk purified igg to naive balb/c mice causes severe exacerbation of hsv-1 induced corneal scarring following ocular challenge. in addition, a productive chronic infection, rather than a latent infection, is found in most trigeminal ganglia. these phenomena are accompanied by a very high t(h)1+t(h)2 response in the eye (ghiasi, h., cai, s., nesburn, a.b., wechsler, ...200010958985
[typing of herpes simplex virus in patients with uveitis].to examine the type of herpes simplex virus (hsv) in cases with uveitis.200010934865
synthesis and antiviral properties of novel analogues of monophosphate and diphosphate bioactive forms of acyclovir.new analogues (compounds 6, 7 and 9) of the mono- (8) and diphosphate (10) bioactive forms of the antiherpes drug acyclovir are described. in compound 6, the monophosphate moiety of 8 was replaced by an aminosulfonyloxy group, while in compounds 7 and 9, a phosphonoacetamidoxy and an o-ethyl phosphonoacetamidoxy moiety are, respectively present instead of the diphosphate one of 10. none of the compounds synthesized proved to possess an appreciable activity on herpes simplex virus (hsv) or human ...200010966166
physiological significance of apoptosis in animal virus infection.in contrast to insect viruses, animal viruses can produce considerable amounts of progeny virus in cells undergoing apoptosis. nevertheless, viruses in general have acquired the ability to escape apoptosis of infected cells. these facts indicate that the role of apoptosis in virus infection is different in insect virus and animal virus, although both viruses need to avoid apoptosis of the infected cells for a viral life cycle in nature. in animal virus infection, the primary role of apoptosis is ...200010967291
novel class of thiourea compounds that inhibit herpes simplex virus type 1 dna cleavage and encapsidation: resistance maps to the ul6 gene.in our search for novel inhibitors of herpes simplex virus type 1 (hsv-1), a new class of thiourea inhibitors was discovered. n-(4-[3-(5-chloro-2,4-dimethoxyphenyl)-thioureido]-phenyl)-acetamide and its 2-fluoro-benzamide derivative inhibited hsv-1 replication. hsv-2, human cytomegalovirus, and varicella-zoster virus were inhibited to a lesser extent. the compounds acted late in the replication cycle by impairing both the cleavage of concatameric viral dna into progeny genome length and the pack ...200010982350
novel hepatotrophic prodrugs of the antiviral nucleoside 9-(2-phosphonylmethoxyethyl)adenine with improved pharmacokinetics and antiviral activity.the device of new hepatotrophic prodrugs of the antiviral nucleoside 9-(2-phosphonylmethoxyethyl)adenine (pmea) with specificity for the asialoglycoprotein receptor on parenchymal liver cells is described. pmea was conjugated to bi- and trivalent cluster glycosides (k(gn)(2) and k(2)(gn)(3), respectively) with nanomolar affinity for the asialoglycoprotein receptor. the liver uptake of the pmea prodrugs was more than 10-fold higher than that of the parent drug (52+/-6% and 62+/-3% vs. 4.8+/-0.7% ...200010973928
the effects of antiviral therapy on the distribution of herpes simplex virus type 1 to ganglionic neurons and its consequences during, immediately following and several months after treatment.both famciclovir (fcv) and valaciclovir (vacv) are potent inhibitors of herpes simplex virus type 1 (hsv-1) in a murine cutaneous infection model. the object of the present study was to determine whether either drug had an effect on the anatomical distribution of infected neurons in the peripheral nervous system and to assess the consequences for infected cells during, immediately following and several months after a 9 day period of continuous treatment. mice were inoculated via the neck with a ...200010993926
[bacterial infection in the conjunctiva of patients with adenoviral conjunctivitis].we evaluate the microbiological features of mixed infection in adenovirus-infected conjunctiva.200010979295
the differential regulation of nitric oxide by herpes simplex virus-1 and -2 in a corneal epithelial cell line.herpes simplex keratitis s a significant cause of blindness worldwide. nitric oxide (no) has been shown to play a role in non-specific defence mechanisms and cell signalling in bacterial and parasitic infections. we investigated if herpes simplex virus (hsv) isolated from keratitis could induce no production. human corneal epithelial cells were infected with high (multiplicity of infection; moi 0.4) and low (moi 0.04) hsv-1 and hsv-2 concentrations. culture supernatants were collected at 1 h, 4 ...200010981795
characterization of glycoprotein c of hszp strain of herpes simplex virus 1.sequences of ul44 genes of strains hszp, kos and 17 of herpes simplex virus 1 (hsv-1) were determined and the amino acid sequences of corresponding glycoproteins (gc) were deduced. in comparison with the 17 strain, the hszp strain showed specific changes in 3 nucleotides and in 2 amino acids (aa 139 and 147, both from arg to trp) in the antigenic locus lii. the change at aa 147 was situated within the gag-binding epitope. in a similar comparison, kos strain had changes in 3 nucleotides and 3 ami ...200010989701
antiherpetic activities of acidic protein bound polysacchride isolated from ganoderma lucidum alone and in combinations with interferons.to investigate antiherpetic activity, an acidic protein bound polysaccharide (apbp) was isolated from carpophores of ganoderma lucidum. this brownish apbp was isolated from water soluble substances of the carpophores by activity-guided isolation method. apbp was tested for its antiviral activity against herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) by plaque reduction assay in tissue culture. apbp showed potent antiviral activity against hsv-1 and hsv-2 in vero cells at its 50% effectiv ...200010996285
possible mode of antiviral activity of acidic protein bound polysaccharide isolated from ganoderma lucidum on herpes simplex viruses.two protein bound polysaccharides, a neutral protein bound polysaccharide (npbp) and an acidic protein bound polysaccharide (apbp), were isolated from water soluble substances of ganoderma lucidum by etoh precipitation and deae-cellulose column chromatography. their antiviral activities against herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) were then investigated by plaque reduction assay. apbp exhibited more potent hsv-1 and hsv-2 antiviral activity than npbp with 50% effective concentr ...200010996289
the essential protein encoded by the ul31 gene of herpes simplex virus 1 depends for its stability on the presence of ul34 protein.to pursue an earlier observation that the protein encoded by the u(l)34 gene binds to intermediate chain of dynein, we constructed a series of mutants from which sequences encoding the entire protein (deltau(l)34) or amino-terminal [u(l)34delta(3-119)] or carboxyl-terminal [u(l)34delta(245-275)] domains were deleted. the mutant lacking the sequence encoding the carboxyl-terminal domain grew in all cell lines tested. the two other mutants replicated only in cell type-dependent manner and poorly. ...200011005871
experimental myelitis in balb/cn and c57bl/6n mice caused by herpes simplex virus type 1 compared with herpes simplex virus type 2.intraperitoneal and footpad inoculations of herpes simplex virus type 1 (hsv) into balb/cn (hsv-susceptible) and c57bl/6n (hsv-resistant) mice were carried out to induce experimental myelitis. standard laboratory strains (mcintyre, f, rk, and recently okinawa strain r1) were inoculated in mice. as a control, the hsv 2 standard laboratory strain sav was also inoculated. the mcintyre strain was the most virulent, while the f strain was the least. rk and r1 were both moderately virulent. myelitis w ...200010997739
analysis of in vitro activities of herpes simplex virus type 1 ul42 mutant proteins: correlation with in vivo function.the dna polymerase (pol) catalytic subunit of herpes simplex virus type 1, encoded by ul30, and its accessory factor, ul42 protein, are both essential for the replication of the virus. because the stable interaction between ul42 and pol renders the pol fully processive for replicative dna synthesis, disruption of this interaction represents a potential goal in the development of novel antiviral compounds. to better compare the effects of mutations in ul42 protein on its known in vitro functions, ...200010998337
herpes simplex virus pneumonia in trauma patients. 200011003335
the herpes simplex virus type 1 fc receptor discriminates between igg1 allotypes.herpes simplex virus type 1 (hsv-1) expresses a complex of two virally encoded glycoproteins, ge and gl, which is capable of binding nonimmune human igg. the ge-gl complex has thus become known as an fc receptor (fcr), which reportedly binds human igg subclasses in the order igg4 > igg1 > or = igg2 and does not bind igg3 from many individuals. there is, however, allelic variation in the genes encoding the human igg1 heavy chain constant region and this gives rise to allotypes of igg1. using reco ...200011009087
amplification of herpes simplex virus type 1 dna in human geniculate ganglia from formalin-fixed, nonembedded temporal bones.polymerase chain reaction (pcr) has provided new insights in molecular biology. recently, some studies have been focused on temporal bone pathology, with amplification of dna from fixed sections of celloidin-embedded bones. the purpose of our study was to elucidate the utility of pcr in detection of minor concentrations of dna from nonoptimal stored samples. we obtained geniculate ganglia from 30 temporal bones preserved in formalin for a long time, without any process of embedding. by performin ...200011020196
alphaherpesvirus proteins related to herpes simplex virus type 1 icp0 affect cellular structures and proteins.the herpes simplex virus type 1 (hsv-1) immediate-early protein icp0 interacts with several cellular proteins and induces the proteasome-dependent degradation of others during infection. in this study we show that icp0 is required for the proteasome-dependent degradation of the nd10 protein sp100 and, as with the other target proteins, the icp0 ring finger domain is essential. further, comparison of the kinetics and icp0 domain requirements for the degradation of pmi and sp100 suggests that a co ...200011024129
differences in determinants required for complex formation and transactivation in related vp16 proteins.vp16-h is an essential structural protein of herpes simplex virus type 1 (hsv-1) and is also a potent activator of virus immediate-early (ie) gene expression. current models of functional determinants within vp16-h indicate that it consists of two domains, an n-terminal domain involved in recruiting vp16-h to a multicomponent dna binding complex with two host proteins, oct-1 and host cell factor (hcf), and an acidic c-terminal domain exclusively involved in transactivation. vp16-e, from equine h ...200011024140
herpes simplex virus type 1 icp0 protein does not accumulate in the nucleus of primary neurons in culture.infected-cell protein 0 (icp0), the product of the herpes simplex virus (hsv) immediate-early (ie) alpha0 gene, is a promiscuous transactivator of viral early (e) and late (l) gene expression. hsv mutants lacking icp0 function are severely deficient in viral growth and protein synthesis, particularly at low multiplicities of infection. early in the infectious process in vitro, icp0 protein accumulates in distinct domains within the nucleus to form characteristic structures active in the transcri ...200011024142
a new positive/negative selectable marker, pudeltatk, for use in embryonic stem cells.a novel positive/negative selection cassette, pudeltatk, was generated. pu(delta)tk is a bifunctional fusion protein between puromycin n-acetyltransferase (puro) and a truncated version of herpes simplex virus type 1 thymidine kinase (deltatk). murine embryonic stem (es) cells transfected with pu(delta)tk become resistant to puromycin and sensitive to 1-(-2-deoxy-2-fluoro-1-beta-d-arabino-furanosyl)-5-iodouracil (fiau). unlike other hsv1 tk transgenes, pudeltatk is readily transmitted through th ...200011020714
a single tube pcr assay for simultaneous amplification of hsv-1/-2, vzv, cmv, hhv-6a/-6b, and ebv dnas in cerebrospinal fluid from patients with virus-related neurological diseases.cerebrospinal fluid (csf) specimens from 27 patients with encephalitis, meningitis, and other neurological diseases were studied for the presence of herpes simplex virus types 1 and 2 (hsv-1/-2), varicella-zoster virus (vzv), cytomegalovirus (cmv), human herpesviruses 6a and 6b (hhv-6a/-6b) and epstein-barr virus (ebv) dna using the polymerase chain reaction (pcr) method. the dnas were amplified using two sets of consensus primer pairs in a single tube, bringing simultaneous amplification of the ...200011031694
plasmid dna-expressed secreted and nonsecreted forms of herpes simplex virus glycoprotein d2 induce different types of immune responses.herpes simplex viruses (hsvs) are significant pathogens and major targets of vaccine development. several attempts have been made to develop prophylactic and therapeutic vaccines for hsv types 1 and 2. although these vaccines elicit strong humoral responses, the overall impact on pathology has been disappointing. an effective vaccine for hsv must induce both humoral and cellular immune responses. dna vaccines are ideal candidates for hsv vaccines because they induce both types of immune response ...200011023455
icp0 induces the accumulation of colocalizing conjugated ubiquitin.herpes simplex virus type 1 (hsv-1) immediate-early protein icp0 is a general activator of viral gene expression which stimulates the initiation of lytic infection and reactivation from quiescence and latency. the importance of icp0 to the biology of hsv-1 infection has stimulated interest in its mode of action. previous studies have reported its interactions with other viral regulatory molecules, with the translation apparatus, with cyclin d3, and with a ubiquitin-specific protease. it has been ...200011024128
a transgenic mouse model for inducible and reversible dysmyelination.oligodendrocytes are glial cells devoted to the production of myelin sheaths. myelination of the cns occurs essentially after birth. to delineate both the times of oligodendrocyte proliferation and myelination, as well as to study the consequence of dysmyelination in vivo, a model of inducible dysmyelination was developed. to achieve oligodendrocyte ablation, transgenic animals were generated that express the herpes virus 1 thymidine kinase (hsv1-tk) gene under the control of the myelin basic pr ...200011027231
rho gtpases and axonal growth cone collapse. 200011036628
different forms of hsv-1 vp22a within purified virion and infected cells.utilizing the monoclonal antibody mca406, our experimental data suggest that the herpes simplex virus type 1 (hsv-1) protein, vp22a, is present in the purified virus in a different form from that present within infected cells, namely the virion and infected-cell form, respectively. it seems reasonable to suggest that two different forms of vp22a are synthesized during the hsv-1 productive cycle. using varying quantities of reducing agents, both inter- and intramolecular disulfide linkages were d ...200011045375
therapy of peritoneal carcinomatosis from colon cancer with oncolytic adenoviruses.the major emphasis on the safety of viral vectors for gene delivery has led to the generally accepted approach of disabling their ability to replicate and thus their potential capacity to spread throughout a tumor by consecutive rounds of infection and lysing neighboring cells.200011045429
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