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antiviral activities of oral 1-o-hexadecylpropanediol-3-phosphoacyclovir and acyclovir in woodchucks with chronic woodchuck hepatitis virus infection.acyclovir triphosphate is a potent inhibitor of hepatitis b virus dna polymerase, but acyclovir treatment provides no benefit in patients with hepatitis b virus infection. this is due in part to the fact that hepatitis b virus, unlike herpes simplex virus, does not code for a viral thymidine kinase which catalyzes the initial phosphorylation of acyclovir. we synthesized 1-o-octadecyl-sn-glycero-3-phospho (3-p)-acyclovir and found that it was highly active in reducing hepatitis b virus replicatio ...200010858362
reduction of aflatoxin b(1) adduct biomarkers by oltipraz in the tree shrew (tupaia belangeri chinensis).the risk of liver cancer is greatest in people both infected with hepatitis b virus (hbv) and highly exposed to aflatoxin b(1) (afb(1)). the tree shrew (tupaia belangeri chinensis) is a unique species that can be infected with human hbv, is susceptible to afb(1)-induced liver cancer, and shows a synergistic interaction between hbv and afb(1) for liver cancer. in this regard, the tree shrew may be useful for evaluating experimental chemoprevention strategies relevant to high-risk human population ...200010799742
the collagen repeat sequence is a determinant of the degree of herpesvirus saimiri stp transforming activity.herpesvirus saimiri (hvs) is divided into three subgroups, a, b, and c, based on sequence divergence at the left end of genomic dna in which the saimiri transforming protein (stp) resides. subgroup a and c strains transform primary common marmoset lymphocytes to interleukin-2-independent growth, whereas subgroup b strains do not. to investigate the nononcogenic phenotype of the subgroup b viruses, stp genes from seven subgroup b virus isolates were cloned and sequenced. consistent with the lack ...200010933720
identification of five different patr class i molecules that bind hla supertype peptides and definition of their peptide binding motifs.we have sequenced the pan troglodytes class i (patr) molecules from three common chimpanzees and expressed them as single molecules in a class i-deficient cell line. these lines were utilized to obtain purified class i molecules to define the peptide binding motifs associated with five different patr molecules. based on these experiments, as well as analysis of the predicted structure of the b and f polymorphic mhc pockets, we classified five patr molecules (patr-a*0101, patr-b*0901, patr-b*0701 ...200011035079
nucleosomes are major t and b cell autoantigens in systemic lupus erythematosus.double-stranded dna (dsdna) is a well-known target of autoantibodies in systemic lupus erythematosus (sle). the majority of these autoantibodies are of the igg isotype and show affinity maturation, both of which are known hallmarks of t cell help. t cell responses to autoantigens, including dna, have been reported only incidentally in sle patients. nevertheless, in murine sle, naked dna and complexed dna (nucleosomes) are known to be recognized by t cells. this study aimed to characterize the an ...200011037891
puumala (puu) hantavirus strain differences and insertion positions in the hepatitis b virus core antigen influence b-cell immunogenicity and protective potential of core-derived particles.hepatitis b virus (hbv) core-derived chimeric particles carrying a puumala (puu) hantavirus (strain vranica/hällnäs) nucleocapsid (n) protein sequence (aa 1-45), alternatively inserted at three distinct positions (n-, c-terminus, or the internal region), and mosaic particles consisting of hbv core as well as core/puu (vranica/hällnäs) n (aa 1-45) readthrough protein were generated. chimeric particles carrying the insert at the n-terminus or the internal region of core induced some protective imm ...200011040127
immune responses to duck hepatitis b virus infection.the duck hepatitis b virus (dhbv) was the first hepatitis b virus identified from an avian host. it is a member of the hepadnaviridae family of viruses. all members of this family display similar genomic organization and replication strategies and cause species-specific infections that result in either transient (acute) or persistent infection. hepadnavirus infection occurs primarily in hepatocytes in the liver with release of infectious virions and non-infectious 'empty' surface antigen particl ...200010717294
combination therapy with lamivudine and adenovirus causes transient suppression of chronic woodchuck hepatitis virus infections.treatment of hepatitis b virus carriers with the nucleoside analog lamivudine suppresses virus replication. however, rather than completely eliminating the virus, long-term treatment often ends in the outgrowth of drug-resistant variants. using woodchucks chronically infected with woodchuck hepatitis virus (whv), we investigated the consequences of combining lamivudine treatment with immunotherapy mediated by an adenovirus superinfection. eight infected woodchucks were treated with lamivudine an ...200011090175
48-mer synthetic peptide analogue of the hepatitis b virus "a" determinant induces an anti-hbs antibody response after a single injection.an extended (48 amino acid) synthetic peptide analogue of the hepatitus b virus (hbv) s protein (hbsag) 'a' determinant has been produced by using 9-fluorenylmethoxycarbonyl (fmoc) chemistry and a low substitution polystyrene resin as the solid phase support. this peptide (s121/48) elicited a sustained anti-peptide antibody response in balb/c (h-2(d)) mice when immunised with freund's complete adjuvant (fca). cross-reactive, anti-hbs antibodies were induced, directed against a significant propor ...200011002244
temporal pathogenesis of experimental neonatal woodchuck hepatitis virus infection: increased initial viral load and decreased severity of acute hepatitis during the development of chronic viral infection.acute hepatitis b virus (hbv) infections either resolve or progress to chronicity. identification of early deviations in host-virus responses associated with these outcomes can further differentiate cause-effect mechanisms that initiate and maintain chronicity. neonatal woodchucks were infected experimentally with the woodchuck hepatitis virus (whv) at 3 days of age. at 8 or 14 weeks of age (i.e. , the early- or mid-acute stage of infection), whole blood and large surgical biopsies of the liver ...200011003627
naturally occurring woodchuck hepatitis virus (whv) deletion mutants in chronically whv-infected woodchucks.deletion mutants of hepatitis b virus (hbv) are often found in chronically hbv-infected patients. it has not been possible to study the significance of such deletion mutants on liver diseases in a suitable animal model. in this study, we characterized naturally occurring deletion mutants of woodchuck hepatitis virus (whv) in 11 chronically whv-infected woodchucks. deletions within the whv pres region (nt 2992-338) had a length of 72 or 84 bp and were located in the amino terminal part of pres1. ...200011080471
high-level synthesis of human prolactin in chinese-hamster ovary cells.two eukaryotic human prolactin (hprl) expression vectors, based on a selectable dihydrofolate reductase (dhfr) marker, were used to transfect dhfr(-) chinese- hamster ovary (cho) cells. one vector, p658-hprl, contains the hepatitis-b virus-x cdna coding for a viral transactivator and sequences mediating dhfr mrna degradation. the other, peddc-hprl, carries the encephalomyocarditis virus leader sequence coupled to hprl cdna to provide high-level protein expression, possibly via a mechanism of int ...200011001873
antiviral efficacy of lobucavir (bms-180194), a cyclobutyl-guanosine nucleoside analogue, in the woodchuck (marmota monax) model of chronic hepatitis b virus (hbv) infection.lobucavir (bms-180194), a cyclobutyl-guanosine nucleoside analogue, effectively reduced whv-viremia in chronically infected carrier woodchucks (marmota monax) by daily per os treatment. whv-viremia in the animals was measured by the serum content of hybridizable whv-genomic dna. lobucavir, given at daily doses of 10 and 20 mg/kg body weight, reduced whv-viremia by a 10- to 200-fold range during therapy. lobucavir, given at 5 mg/kg, suppressed whv-viremia by a 10- to 30-fold range, whereas a 0.5 ...200011164506
immune responses following simian/human immunodeficiency virus (shiv) challenge of rhesus macaques after human immunodeficiency virus (hiv)-1 third variable domain (v3) loop-based genetic immunization.following dna immunization of rhesus macaques with a plasmid encoding the human immunodeficiency virus (hiv)-1 third variable domain (v3) loop, presented by pseudo-viral envelope particles of hepatitis b virus, specific immune responses were induced. the primates were then inoculated with a chimeric simian/human immunodeficiency virus (shiv). all the animals were infected, but the v3-specific immunization provided a relative attenuation of the acute phase of infection in the absence of neutraliz ...200011168828
generation and characterization of a novel tetravalent bispecific antibody that binds to hepatitis b virus surface antigens.hepatitis b virus (hbv) infection is a worldwide public health problem affecting about 350 million people. hbv envelope contains three surface antigens, called pre-s1, pre-s2 and s. for the prophylaxis of hbv infection, only an anti-s monoclonal antibody was tested for the protective efficacy against hbv infection, but it was shown to be incomplete. in addition, some immune escape mutants carrying mutations on the s antigen were reported. therefore, a multivalent bispecific antibody rather than ...200011451417
[the feature of influenza virus activity and genetic characterization of ha1 gene of influenza a h3n2 viruses isolated from 1994-1997 in shenzhen].to understand the feature of influenza virus activity and genetic characterization of ha1 gene of influenza a h3n2 viruses isolated in recently years in shenzhen.199912569759
a new avian hepadnavirus infecting snow geese (anser caerulescens) produces a significant fraction of virions containing single-stranded dna.we describe the identification and functional analysis of an evolutionary distinct new avian hepadnavirus. infection of snow geese (anser caerulescens) with a duck hepatitis b virus (dhbv)-related virus, designated sghbv, was demonstrated by detection of envelope proteins in sera with anti-dhbv pres and s antibodies. comparative sequence analysis of the pcr-amplified sghbv genomes revealed unique sghbv sequence features compared with other avian hepadnaviruses. unlike dhbv, sghbv shows an open r ...199910489339
the expression of insulin-like growth factor ii, hepatitis b virus x antigen and p21 in experimental hepatocarcinogenesis in tree shrews.the purpose of this paper was to study the mechanism of synergistic effect in hepatocarcinogenesis induced by hepatitis b virus (hbv) infection and aflatoxin b1 (afb1) intake. immunohistochemical staining was used in formalin-fixed, paraffin-embedded sections of cancer and liver tissues. the incidence of hepatocellular carcinomas (hccs) was 52.9% in experimental tree shrews that received both hbv and afb1. it was significantly higher than that of animals exposed to hbv (11.1%, group b), or (afb1 ...199910374027
evaluation of immune responses to inactivated influenza vaccines prepared in embryonated chicken eggs and mdck cells in a mouse model.this study was initiated with the isolation of influenza a and b viruses from clinical throat swabs in both fertile chicken eggs (egg) and mdck cells, which were used in subsequent vaccine production in the above two hosts. on the basis of haemagglutination-inhibiting (hi) tests, immune mouse sera from mice vaccinated with mdck cell-derived vaccines revealed antigenic similarities among h3n2 or b viruses isolated in mdck cells or eggs. similarly, antiserum prepared by immunization with egg-deriv ...199910494959
unraveling hepatitis b virus infection of mice and men (and woodchucks and ducks) 199910502809
hepatitis b virus x protein: structure, function and biology.the x gene is conserved among mammalian hepadnaviruses and the x protein, px, is essential for viral propagation at least in the woodchuck. during the last decade, efforts have centered on elucidating the oncogenic role of px in hepatitis b virus infection. the accumulating knowledge on px indicates that it is a multifunctional regulatory protein which modulates many host functions by communicating directly or indirectly with a variety of host targets as is the case for many viral regulatory pro ...199910516464
fusogenic activity of hepadnavirus peptides corresponding to sequences downstream of the putative cleavage site.sequence homology between the amino-terminal region of the s protein of hepatitis b virus (hbv) and known fusion peptides from retroviruses and paramyxoviruses led us to propose that this region might be equally involved in the initial infective steps of hepadnaviruses. in fact, we showed that a synthetic peptide corresponding to the n-terminus region of the s protein of hbv had membrane-interacting properties and was able to induce liposome fusion adopting an extended (beta-sheet) conformation ...199910441561
activation of the n-myc2 oncogene by woodchuck hepatitis virus integration in the linked downstream b3n locus in woodchuck hepatocellular carcinoma.in the woodchuck hepatitis virus (whv)/woodchuck model for hepatitis b virus-induced hepatocellular carcinoma, frequent activation of n-myc oncogenes by whv integration has been firmly established. n-myc2, the most frequently affected gene, was reported to be activated by whv insertion either in the proximity of the gene or in a distant uncoding locus, win. we previously reported that a whv integration cloned from a liver tumor was located in a chromosomal locus already described by others as th ...199910329558
phyllanthus orbicularis aqueous extract: cytotoxic, genotoxic, and antimutagenic effects in the cho cell line.the present work evaluates the cytotoxic, genotoxic, and antimutagenic effects of phyllanthus orbicularis (plant of genus phyllantus) aqueous extract in chinese hamster ovary (cho) cells. p. orbicularis aqueous extracts are used in cuban traditional medicine for their antiviral activity against hepatitis b virus and a and b flu virus. the cytotoxicity of the extract was tested by means of colony-forming ability and growth-inhibition assays as well as by measuring the mitotic index. apoptosis ind ...199910620480
persistence of infectious hepadnavirus in the offspring of woodchuck mothers recovered from viral hepatitis.mother-to-child transmission is an important route for hepatitis b virus (hbv) dissemination. it has been established that hbv traces persist for years after complete clinical recovery from hepatitis b. similarly, resolution of hepatitis caused by hbv-related woodchuck hepatitis virus (whv) is followed by occult lifelong carriage of pathogenic virus. in this study, we documented that whv persisting after termination of acute hepatitis is transmittable to newborns as an asymptomatic long-term inf ...199910411550
perspectives for the treatment of hepatitis b virus infections.primarily resulting as a spin-off of the search for effective anti-hsv or anti-hiv agents, several compounds have been identified as effective and promising candidate anti-hbv drugs, i.e. famciclovir (penciclovir), bms-200475, lamivudine (3tc), (-)ftc, l(-)fd4c, l-fmau, dapd (dxg), bis(pom)-pmea and bis(poc)-pmpa. they all inhibit hbv replication in hep g2 2.2.15 at concentrations that are well below the cytotoxicity threshold. all these nucleoside analogues require three phosphorylation steps t ...199910418752
occult lifelong persistence of infectious hepadnavirus and residual liver inflammation in woodchucks convalescent from acute viral hepatitis.traces of hepatitis b virus (hbv) genome can persist for years following recovery from hepatitis b. to determine overall duration, molecular characteristics, and pathological implications of this serologically undetectable form of hepadnaviral carriage, we have analyzed the expression of transcriptionally active virus genomes, their infectivity, and examined liver alterations during the natural lifespan of woodchucks convalescent from acute infection with hbv- related woodchuck hepatitis virus ( ...199910051500
recombinant duck interferon gamma inhibits duck hepatitis b virus replication in primary hepatocytes.interferon gamma (ifn-gamma), which has been cloned in several mammalian species and recently in birds, plays a critical role in modulating immune system function. ifn-gamma and tumor necrosis factor alpha (tnf-alpha) have been shown to be crucial in the pathogenesis of viral hepatitis and in the transient disappearance of hepatitis b virus (hbv) from the liver after adoptive transfer of hbv-specific cytotoxic t lymphocytes into hbv-transgenic mice. similar studies in the natural animal hosts of ...199910074168
a new group of hepadnaviruses naturally infecting orangutans (pongo pygmaeus).a high prevalence (42.6%) of hepatitis b virus (hbv) infection was suspected in 195 formerly captive orangutans due to a large number of serum samples which cross-reacted with human hbv antigens. it was assumed that such viral infections were contracted from humans during captivity. however, two wild orangutans were identified which were hbv surface antigen positive, indicating that hbv or related viruses may be occurring naturally in the orangutan populations. sequence analyses of seven isolate ...199910438880
kemri hep-cell ii hepatitis b surface antigen screening kit.kenya is a high hepatitis b virus (hbv) endemic zone. prevention of hbv transmission by transfusing safe blood is necessary. kits for screening hepatitis b surface antigen (hbsag) are usually imported and are expensive. hence it has been difficult to screen donated and patient blood samples all over kenya.199910685326
identification and expression of glycine decarboxylase (p120) as a duck hepatitis b virus pre-s envelope-binding protein.a 120-kilodalton protein (p120) was identified in the duck liver that binds to several truncated versions of duck hepatitis b virus (dhbv) pre-s envelope protein, suggesting p120 may serve as a dhbv co-receptor. the amino acid sequences of tryptic peptides from purified p120 were found to be the duck p protein of the glycine decarboxylase complex (dgd). dgd cdna cloning revealed extensive protein conservation with the chicken homologue except for several insertions in the n-terminal leader seque ...199910488106
synergistic effect of hepatitis b virus and aflatoxin b1 in hepatocarcinogenesis in tree shrews.an animal experiment with tree shrews was performed to detect the synergistic effects of hepatitis b virus (hbv) infection and dietary aflatoxin b1 (afb1) in hepatocarcinogenesis. adult healthy tree shrews (tupaia belangeri chinensis) were divided into four groups: group a (hbv + afb1)--animals were infected with human hbv serum at first, then fed afb1 diluted with milk, 150 ug/kg.bw/day, 6 days/week for 105 weeks. group b (hbv)--animals were infected with human hbv as group a, but no afb1 treat ...199910374028
new chimaeric hepatitis b virus core particles carrying hantavirus (serotype puumala) epitopes: immunogenicity and protection against virus challenge.virus-like particles generated by the heterologous expression of virus structural proteins are able to potentiate the immunogenicity of foreign epitopes presented on their surface. in recent years epitopes of various origin have been inserted into the core antigen of hepatitis b virus (hbv) allowing the formation of chimaeric hbv core particles. chimaeric core particles carrying the 45 n-terminal amino acids of the puumala hantavirus nucleocapsid protein induced protective immunity in bank voles ...199910486924
pharmacokinetics of beta-l-2',3'-dideoxy-5-fluorocytidine in rhesus monkeys.beta-l-2',3'-dideoxy-5-fluorocytidine (beta-l-fddc), a novel cytidine analog with an unnatural beta-l sugar configuration, has been demonstrated by our group and others to exhibit highly selective in vitro activity against human immunodeficiency virus types 1 and 2 and hepatitis b virus. this encouraging in vitro antiviral activity prompted us to assess its pharmacokinetics in rhesus monkeys. three monkeys were administered an intravenous dose of [3h] beta-l-fddc at 5 mg/kg of body weight. follo ...199910103200
hepadnavirus evolution and molecular strategy of adaptation in a new host.in order to elucidate the mechanisms of hepadnavirus evolution in vivo and to trace the fate of known quasispecies in a single animal during the acute phase of infection, a woodchuck (marmota monax) was infected with the hepadnavirus woodchuck hepatitis b virus (whv). woodchuck 197 (w197) was injected intravenously with pooled sera collected from a chronic carrier that had been infected originally with a molecular clone of known genome sequence (whv7). viral genome variants from both the inoculu ...199910092000
b-virus specific-pathogen-free breeding colonies of macaques (macaca mulatta): retrospective study of seven years of testing.national institutes of health's division of comparative medicine has sponsored a multi-institutional program for the establishment of specific-pathogen-free (spf) macaque colonies. b virus (herpesvirus simiae, cercopithecine herpesvirus type 1) has been targeted in this surveillance. participating institutions have established individual timetables for frequency of testing and types of monitoring and husbandry techniques, all with the common goal of producing pathogen-free monkeys for research. ...199910331543
[experimental study of residual virulence of viral vaccine strains].residual virulence of three vaccinia strains: neurovaccine, l-ivp, and its recombinant revacs-b expressing hbs and pres2 antigens of hepatitis b virus is compared. insertion of hbs and pres2 antigens of hepatitis b virus in the genome of vaccinia virus strain l-ivp decreases its residual virulence and leads to a benign course of vaccinal reaction involving no deaths of rabbits, cotton rats, or guinea pigs. we may expect that recombinant vaccine revacs b based on l-ivp strain will cause no postva ...199910358902
double-stranded linear duck hepatitis b virus (dhbv) stably integrates at a higher frequency than wild-type dhbv in lmh chicken hepatoma cells.integration of hepadnavirus dnas into host chromosomes can have oncogenic consequences. analysis of host-viral dna junctions of dhbv identified the terminally duplicated r region of the viral genome as a hotspot for integration. since the r region is present on the 5' and 3' ends of double-stranded linear (dsl) hepadnavirus dnas, these molecules have been implicated as integration precursors. we have produced a lmh chicken hepatoma cell line (lmh 66-1 dsl) which replicates exclusively dsl duck h ...19999882355
treatment of chronic hepadnavirus infection in a woodchuck animal model with an inhibitor of protein folding and trafficking.a novel strategy for anti-viral intervention of hepatitis b virus (hbv) through the disruption of the proper folding and transport of the hepadnavirus glycoproteins is described. laboratory reared woodchucks chronically infected with woodchuck hepatitis virus (whv) were treated with n-nonyl-deoxynojirimycin (n-nonyl-dnj), an inhibitor of the endoplasmic reticulum (er) alpha-glucosidases. the woodchucks experienced significant dose dependent decreases in enveloped whv, resulting in undetectable a ...19989585237
[hepatitis b virus and hepatocellular carcinoma].hepatitis b is a very important public health problem. epidemiologic studies have shown a relationship between the hepatitis b virus (hbv) chronic carrier state and the development of hepatocellular carcinoma. hbv belongs to the hepadna viruses family which includes the woodchuck hepatitis virus (whv), woodchucks infected with whv represent a good experimental model to study the viral oncogenesis. in 85% of the studied cases, whv acts by insertional mutagenesis in a gene of the myc family, mostl ...19989622933
cytokeratin expression is reduced in glycogenotic clear hepatocytes but increased in ground-glass cells in chronic human and woodchuck hepadnaviral infection.hepatocytes of normal adult liver express cytokeratins (cks) 8/18, but bile duct cells additionally contain ck7/19. we have previously demonstrated the frequent occurrence of foci of altered hepatocytes in association with hepatic tumors in humans and provided evidence for a preneoplastic nature of the focal lesions. in this study, we investigated the ck expression in both the preneoplastic lesions and extrafocal parenchyma. sixty-seven explanted livers with cirrhosis or advanced fibrosis harbor ...19989695996
woodchuck hepatitis virus contains a tripartite posttranscriptional regulatory element.the hepatitis b virus posttranscriptional regulatory element (hbvpre) is a cis-acting rna element that partially overlaps with enhancer i and is required for the cytoplasmic accumulation of hbv surface rnas. we find that the closely related woodchuck hepatitis virus (whv), which has been shown to lack a functional enhancer i, also contains a posttranscriptional regulatory element (wpre). deletion analysis suggests that the wpre consists of three independent subelements. comparison of the biparti ...19989573279
the gdpal region of the pre-s1 envelope protein is important for morphogenesis of woodchuck hepatitis virus.the pre-s envelope protein of duck hepatitis b virus (dhbv) contains a region, asp-asp-pro-leu-leu (ddpll), that is specifically required for virus assembly and secretion (lenhoff and summers, j virol 1994;68:4565-4571). we found that amino acids 201 to 205 of the pre-s envelope protein of woodchuck hepatitis virus (whv) form a conserved amino acid cluster, gly-asp-pro-ala-leu (gdpal), which resembles the ddpll sequence of dhbv. to determine whether the gdpal region was functionally equivalent t ...19989581699
isolation of a hepadnavirus from the woolly monkey, a new world primate.hepatitis b virus (hbv) infections are a major worldwide health problem with chronic infections leading to cirrhosis and liver cancer. viruses related to human hbv have been isolated from birds and rodents, but despite efforts to find hepadnaviruses that infect species intermediate in evolution between rodents and humans, none have been described. we recently isolated a hepadnavirus from a woolly monkey (lagothrix lagotricha) that was suffering from fulminant hepatitis. phylogenetic analysis of ...19989576957
chimaeric hbv core particles carrying a defined segment of puumala hantavirus nucleocapsid protein evoke protective immunity in an animal model.hantaviruses are rodent-born agents which are pathogenic in humans causing haemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome. to induce a protective immunity against a european hantavirus (puumala) we constructed chimaeric hepatitis b virus (hbv) core particles carrying defined fragments of the puumala virus nucleocapsid protein. after immunisation of bank voles, the natural host of puumala virus, with core particles possessing an insertion of the n-terminal part of puumala ...19989607042
woodchuck hepatitis virus enhancer i and enhancer ii are both involved in n-myc2 activation in woodchuck liver tumors.direct activation of the n-myc2 oncogene by insertion of woodchuck hepatitis virus (whv) dna is a major oncogenic step in woodchuck hepatocarcinogenesis. we previously reported that whv enhancer ii (we2), which controls expression of the core/pregenome rna, can also activate the n-myc2 promoter in hepatoma cell lines. to better define the integrated whv regulatory sequences responsible for n-myc2 promoter activation in woodchuck liver tumors, we analyzed the structure and enhancer activity of a ...19989621085
[development of a method for creating a colony of macaca mulatta, free of herpes b virus infection].to form the colony of monkeys, free of herpes b virus, the serological study was made with the aim of finding out the carriers of this virus. 482 rhesus macaques (macaca mulatta) from the adler monkey house were examined for the presence of antibodies to herpes b virus by the method of point immunoblotting with the use of herpes virus simiae as antigen. the contamination of monkeys in different open-air cages varied from 12.5% to 92%. in different age groups, it was 27% in nonpubescent monkeys ( ...19989700888
[the serologic detection of virus-induced infections in the domestic goose (anser anser dom.)].the most important virus-induced diseases associated with heavy losses in the domestic goose are derzsy's disease which is caused by a goose parvovirus and duck plague (duck viral enteritis) which is caused by an avian herpesvirus. both diseases still occur but can be prevented by timely vaccinations. antibodies against influenza a viruses of the subtypes h1, h5, and h7 as well as against avian paramyxoviruses of the serogroups 4, 6, and 8, respectively, were not detected in any of the examined ...19989710927
genetic immunization of chimpanzees chronically infected with the hepatitis b virus, using a recombinant retroviral vector encoding the hepatitis b virus core antigen.cytotoxic t lymphocyte (ctl) activity and cd4+ helper t cell responses to the hepatitis b virus (hbv) core antigen (hbcag) have been implicated in clearance of acute and chronic hbv infections. we showed that intramuscular injections of a novel recombinant retroviral vector expressing an hbcag-neomycin phosphotransferase ii (hbc-neo) fusion protein induces hbc/eag-specific antibodies and cd4+ and cd8+ t cell responses in mice and rhesus monkeys. we have now immunized three chronically infected c ...19989721082
molecular evidence for distinct genotypes of monkey b virus (herpesvirus simiae) which are related to the macaque host species.although monkey b virus (herpesvirus simiae; bv) is common in all macaque species, fatal human infections appear to be associated with exposure to rhesus macaques (macaca mulatta), suggesting that bv isolates from rhesus monkeys may be more lethal to nonmacaques than are bv strains indigenous to other macaque species. to determine if significant differences that would support this supposition exist among bv isolates, we compared multiple bv strains isolated from rhesus, cynomolgus, pigtail, and ...19989765470
prevalence of herpes b virus antibody in nonhuman primates reared at the national university of japan.a serological investigation by means of an enzyme immuno assay test for herpes b virus (cercopithecine herpesvirus 1) was performed on 961 sera of healthy nonhuman primates reared in laboratory animal facilities which belong to the association of laboratory animal facilities of the national university of japan. an antibody prevalence of 40% (384/ 961) was demonstrated. the antibody titer was shown to be higher among macaques (60% of cynomolgus monkeys, 53% of rhesus monkeys, and 34% of japanese ...19989816497
inhibition of human hepatitis b virus replication by at-61, a phenylpropenamide derivative, alone and in combination with (-)beta-l-2',3'-dideoxy-3'-thiacytidine.at-61, a member of a novel class of phenylpropenamide derivatives, was found to be a highly selective and potent inhibitor of human hepatitis b virus (hbv) replication in four different human hepatoblastoma cell lines which support the replication of hbv (i.e., hepad38, hepad79, 2.2.15, and transiently transfected hepg2 cells). this compound was equally effective at inhibiting both the formation of intracellular immature core particles and the release of extracellular virions, with 50% effective ...19989835512
retrovirus receptor pit-1 of the felis catus.we isolated a cdna encoding a feline homolog of human pit-1, a sodium-dependent phosphate symporter which is utilized by gibbon ape leukemia virus (galv) as a receptor for entry into host cells. the overall homology between the human and feline receptors is 92 and 93% at the nucleotide and deduced amino acid levels, respectively. hydropathy analyses implied ten potential membrane spanning regions and, in analogy to human and murine homologs, five extracellular and four intracellular loops. strik ...19989878855
fatal cercopithecine herpesvirus 1 (b virus) infection following a mucocutaneous exposure and interim recommendations for worker protection.on december 10, 1997, a 22-year-old female worker at a primate center died from cercopithecine herpesvirus 1 (b virus) infection 42 days after biologic material (possibly fecal) from a rhesus macaque (macaca mulatta) splashed into her right eye. this report summarizes the clinical features of her illness and the subsequent investigation by cdc in response to a technical assistance request from the occupational safety and health administration (osha) and presents interim recommendations to preven ...19989879633
immunogenicity and protective efficacy in mice of influenza b virus vaccines grown in mammalian cells or embryonated chicken eggs.the immunogenicity and protective efficacy of formalin-inactivated influenza b/memphis/1/93 virus vaccines propagated exclusively in vero cells, mdck cells, or embryonated chicken eggs (hereafter referred to as eggs) were investigated. mammalian cell-grown viruses differ from the egg-grown variant at amino acid position 198 (pro/thr) in the hemagglutinin gene. the level of neuraminidase activity was highest in egg-grown virus, while mdck and vero cell-derived viruses possessed 70 and 90% less ac ...19989557744
preclinical investigation of l-fmau as an anti-hepatitis b virus agent.preclinical aspects of a potent anti-hepatitis b virus (hbv) l-nucleoside, 1-(2-fluoro-5-methyl-beta-l-arabino-furanosyl)uracil (l-fmau) are described. l-fmau was prepared from l-ribose derivatives via either l-xylose or l-arabinose. l-fmau shows potent antiviral activity against hepatitis b virus (ec50 5.0 microm in h1 cells) with high selectivity in vitro. l-fmau is not incorporated into mitochondrial dna and no significant lactic acid production was observed in vitro. l-fmau is phosphorylated ...199810726061
experimental study on pathogenicity of precore mutants in hepadnaviridae.to study the replicative competency and pathogenicity of precore gene mutants of duck hepatitis b virus (dhbv) in the duck model.199811245071
antiviral activity and toxicity of fialuridine in the woodchuck model of hepatitis b virus infection.woodchucks were used to study the antiviral activity and toxicity of fialuridine (fiau; 1,-2'deoxy-2'fluoro-1-beta-d-arabinofuranosyl-5-iodo-uracil). in an initial experiment, groups of six chronic woodchuck hepatitis virus (whv) carrier woodchucks received daily doses of fiau by intraperitoneal injection for 4 weeks. at 0.3 mg/kg/d, the antiviral effect was equivocal, but at 1.5 mg/kg/d, fiau had significant antiviral activity. no evidence of drug toxicity was observed during the 4-week period ...19989657111
in vivo induction of specific cytotoxic t lymphocytes in mice and rhesus macaques immunized with dna vector encoding an hiv epitope fused with hepatitis b surface antigen.dna immunization offers a novel means to induce humoral and cellular immunity in inbred or in outbred animals. here we have tested the efficiency of genetic immunization with hepatitis b virus (hbv) envelope-based vectors. in naive primates, injection of a plasmid dna encoding hbv envelope proteins induced an hbv-specific cytotoxic response and appearance of potentially protective anti-hbs antibodies. moreover, intramuscular and intradermal injections of a dna expression vector encoding an epito ...19989454704
structure and glycosylation patterns of surface proteins from woodchuck hepatitis virus.woodchucks chronically infected with woodchuck hepatitis virus (whv) are a valuable model for human hepatitis b virus (hbv) in studies of pathogenesis, immunity, and antiviral therapy. for this reason, substantial efforts to characterize both the similarities and the differences between hbv and whv are being made. the structure of the whv surface proteins (whs proteins) has not yet been adequately elucidated. the bands that would be expected for glycosylated and nonglycosylated small (s) whs pro ...19989811735
in vitro inhibition of hepadnavirus polymerases by the triphosphates of bms-200475 and lobucavir.the guanosine analogs bms-200475 and lobucavir have previously been shown to effectively suppress propagation of the human hepatitis b virus (hbv) and woodchuck hepatitis virus (whv) in 2.2.15 liver cells and in the woodchuck animal model system, respectively. this repression was presumed to occur via inhibition of the viral polymerase (pol) by the triphosphate (tp) forms of bms-200475 and lobucavir which are both produced in mammalian cells. to determine the exact mode of action, bms-200475-tp ...19989835515
efficacy of the carbocyclic 2'-deoxyguanosine nucleoside bms-200475 in the woodchuck model of hepatitis b virus infection.daily oral treatment with the cyclopentyl 2'-deoxyguanosine nucleoside bms-200475 at doses ranging from 0.02 to 0.5 mg/kg of body weight for 1 to 3 months effectively reduced the level of woodchuck hepatitis virus (whv) viremia in chronically infected woodchucks as measured by reductions in serum whv dna levels and endogenous hepadnaviral polymerase activity. within 4 weeks of daily therapy with 0.5 or 0.1 mg of bms-200475 per kg, endogenous viral polymerase levels in serum were reduced about 1, ...19989835516
antiviral activity of ganciclovir, 9-(1,3-dihydroxy-2-propoxymethyl) guanine against woodchuck hepatitis virus: quantitative measurement of woodchuck hepatitis virus dna using storage phosphor technology.ganciclovir is a nucleoside analogue active against cytomegalovirus. the compound has also shown in vitro and in vivo activity against duck hepatitis b virus. we investigated the ability of ganciclovir to inhibit another hepadnaviridae, the woodchuck hepatitis virus, which is the most closely related with hepatitis b virus. we compared two different quantification methods of woodchuck hepatitis virus dna.19989836108
pharmacodynamics of (-)-beta-2',3'-dideoxy-3'-thiacytidine in chronically virus-infected woodchucks compared to its pharmacodynamics in humans.the pharmacodynamics of (-)-beta-2',3'-dideoxy-3'-thiacytidine (3tc) was studied in chronically woodchuck hepatitis virus-infected woodchucks and compared to that in previous studies in hepatitis b virus (hbv)-infected humans. net depletion rates of serum virus dna in woodchucks receiving 3tc were modeled as a sum of an exponentially declining virus input and a first-order elimination. preceding shoulders and pseudo-first-order virus half-lives in serum ranged from 1 to 7 days and were dose depe ...19989797207
characterization of chimeric antibody producing cho cells in the course of dihydrofolate reductase-mediated gene amplification and their stability in the absence of selective pressure.recombinant chinese hamster ovary (cho) cells expressing a high-level of chimeric antibody against s surface antigen of hepatitis b virus were obtained by co-transfection of heavy and light chain cdna expression vectors into dihydrofolate reductase (dhfr)-deficient cho cells and subsequent gene amplification in medium containing stepwise increments in methotrexate (mtx) level such as 0.02, 0.08, 0.32, 1.0, and 4.0 microm. the highest producer (hp) subclone was isolated from each mtx level and wa ...199810099263
metabolic labeling of woodchuck hepatitis b virus x protein in naturally infected hepatocytes reveals a bimodal half-life and association with the nuclear framework.in order to identify potential sites of hepadnavirus x protein action, we have investigated the subcellular distribution and the stability of woodchuck hepatitis virus (whv) x protein (whx) in primary hepatocytes isolated from woodchucks with persistent whv infection. in vivo cell labeling and cell fractionation studies showed that the majority of whx is a soluble cytoplasmic protein while a minor part of newly synthesized whx is associated with a nuclear framework fraction (20%) and with cytosk ...19989765489
[clinical and experimental study on treatment of chronic hepatitis b with yanggan aoping mixture].to assess the efficacy of yanggan aoping mixture (ygapm) in treating hepatitis b.19979863082
development of replicative and nonreplicative hepatitis b virus vectors.to investigate the possibility of using hepatitis b virus (hbv) as a vector, the tat gene from human immunodeficiency virus type 1 (hiv-1) was inserted into the full-length hbv genome in-frame with the polymerase (pol) open reading frame in the tether region and downstream of the pres1 promoter. we demonstrated that the tat gene was expressed with full activity in transactivating the hiv-1 long terminal repeat (ltr). the expression of the tat gene in the context of the hbv genome in chicken hepa ...19979472557
differential regulation of the pre-c and pregenomic promoters of human hepatitis b virus by members of the nuclear receptor superfamily.synthesis of the pre-c and pregenomic rnas of human hepatitis b virus (hbv) is directed by two overlapping yet separate promoters (x. yu and j. e. mertz, j. virol. 70:8719-8726, 1996). previously, we reported the identification of a binding site for the nuclear receptor hepatocyte nuclear factor 4 (hnf4) spanning the tata box-like sequence of the pre-c promoter. this hnf4-binding site consists of an imperfect direct repeat of the consensus half-site sequence 5'-aggtca-3' separated by one nucleot ...19979371596
fatal disseminated cercopithecine herpesvirus 1 (herpes b infection in cynomolgus monkeys (macaca fascicularis).two adult female cynomolgus monkeys (macaca fascicularis) that had been housed together for 4 months died within 2 weeks of each other after brief illnesses. monkey no. 1 presented with collapse, watery stool, and hypothermia and died overnight. monkey no. 2 presented with dyspnea, nasal discharge, leukopenia, and hypoproteinemia and was euthanized after 2 days. both animals had peritoneal effusions, massive necrosis of pharyngeal, esophageal, and gastric mucosa, and multifocal hepatic and pancr ...19979381651
prevalence of herpesvirus papio 2 in baboons and identification of immunogenic viral polypeptides.the prevalence of herpesvirus papio 2 (hvp2) in several groups of captive and wild-caught baboons was determined by detection of anti-hvp2 antibodies in 133 sera of adult baboons. over 90% of newly imported (wild-caught) adult olive baboons (papio anubis) from kenya and chacma baboons (p. ursinus) from south africa were found to have anti-hvp2 titers. similarly, approximately 85% of captive breeding colony baboons (p. anubis and p. cynocephalus) were seropositive for hvp2. infected animals were ...19979241626
cooperative binding of nf-y and sp1 at the dnase i-hypersensitive site, fatty acid synthase insulin-responsive element 1, located at -500 in the rat fatty acid synthase promoter.in vitro dnase i footprint analysis of the rat fatty acid synthase (fas) promoter from -568 to -468 revealed four protein binding sites: a, b, and c boxes and the fas insulin-responsive element 1 (fire1). as demonstrated by gel mobility shift analysis and supershift experiments, fire1, located between -516 and -498, is responsible for binding nf-y. the c box located downstream of fire1 was shown by in vitro footprinting to be a sp1 binding site, and furthermore, competition with sp1 also abolish ...19979261184
a novel transcriptional element in circular dna monomers of the duck hepatitis b virus.we report the presence of two elements, pet and net, that are required for proper transcription of the duck hepatitis b virus (dhbv). these regions were previously identified by using plasmid clones of the virus in transient expression assays (m. huang and j. summers, j. virol. 68:1564-1572, 1994). in this study, we further analyzed these regions by using in vitro-synthesized circular dhbv dna monomers to mimic the authentic transcriptional template. we observed that pet was required for pregeno ...19979311882
pharmacokinetics of 1-(2-fluoro-5-methyl-beta-l-arabinofuranosyl)uracil in woodchucks.1-(2-fluoro-5-methyl-beta-l-arabinofuranosyl)uracil (l-fmau) is a nucleoside analog with potent in vitro activity against hepatitis b virus (hbv) and epstein-barr virus. the purpose of this study was to characterize the disposition of l-fmau following oral and intravenous administration in the woodchuck animal model. the numerous similarities between woodchuck hepatitis virus and hbv infection justify the use of the woodchuck as an animal model for preclinical studies of anti-hbv agents in vivo. ...19979333045
characterization of t-cell response to woodchuck hepatitis virus core protein and protection of woodchucks from infection by immunization with peptides containing a t-cell epitope.specific activation of t cells appears to be a prerequisite for viral clearance during hepatitis b virus (hbv) infection. the t-cell response to hbv core protein is essential in determining an acute or chronic outcome of hbv infection, but how this immune response contributes to the course of infection remains unclear. this is due to results obtained from humans, which are restricted to phenomenological observations occurring during the clinical onset after hbv infection. thus, a useful animal m ...19978985324
characterization of cd8+ cytotoxic t-lymphocyte responses after genetic immunization with retrovirus vectors expressing different forms of the hepatitis b virus core and e antigens.cytotoxic t-lymphocyte (ctl) activity appears to play an important role in resolving hepatitis b virus (hbv) infection, and the ability to induce such responses remains an important goal for developing effective immunotherapeutics. a panel of recombinant retrovirus vectors expressing different forms of the hbv core antigen (hbcag) or e antigen (eag) were found to induce antigen-specific major histocompatibility complex-restricted ctl responses in both mice and macaques. in addition, a novel retr ...19979094605
major differences between whv and hbv in the regulation of transcription.studies were carried out to further characterize enhancer and promoter elements on the woodchuck hepatitis virus (whv) genome. we were able to confirm the existence of whv promoters analogous to the major promoters of the related human hepatitis b virus (hbv) and of an enhancer analogous to the recently described whv e2 element (ueda, k., wei, y., and ganem, d., virology 217, 413, 1996). however, we were unable to identity an enhancer analogous to the e1 element of (hbv), despite the fact that t ...19979123867
mapping of the cellular immune responses to woodchuck hepatitis core antigen epitopes in chronically infected woodchucks.t-cell responses to hepatitis b virus nucleocapsid antigens (hbcag and hbeag) play an important role in disease outcome in those infected with hepatitis b virus (hbv). the woodchuck is naturally infected in the wild with woodchuck hepatitis virus (whv), which shows a high degree of genetic homology to hbv and produces a similar pattern of infection in its natural host. twenty-three overlapping peptides were constructed to cover the entire whv core region and used to identify immunodominant cellu ...19979179757
the hepatitis b virus x gene potentiates c-myc-induced liver oncogenesis in transgenic mice.the hepatitis b virus x protein (hbx) is thought to be implicated in the development of hepatocellular carcinoma, but its exact function remains controversial. transgenic mice from pex7 and ax16 lineages that express hbx in the liver under control of different viral regulatory elements develop no liver pathology (billet et al., 1995). we have crossed these two mouse lineages with whv/c-myc oncomice in which liver-specific expression of c-myc driven by woodchuck hepatitis virus (whv) regulatory s ...19979053836
hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-l-lysine. synthesis of the carrier and pharmacological properties of the conjugate.the hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-l-lysine (l-poly(lys)) must have a high solubility in order to be injected in a small volume compatible with the intramuscular route. in this paper the molecular weights of poly(lys) which allowed the synthesis of conjugates with the properties of high solubility and limited loss by the kidney were determined and a procedure for obtaining poly(lys) preparations with the required range of polymerization has b ...19979059943
hepatitis b virus pres1 functions as a transcriptional activation domain.hepatitis b virus (hbv) pres1 fused to the gal4 dna-binding domain functioned as a transcriptional activation domain in yeast and mammalian cells. the gal4-pres1 fusion proteins derived from the pres1 of all three tested hbv subtypes (adr, adw and ayw) specifically activated the transcription of a lacz or chloramphenicol acetyltransferase reporter gene linked to a gal4-responsive promoter in transient transfection assays using yeast or hepg2 cells, respectively. deletion analyses showed that the ...19979152426
in vitro neutralization of hepatitis b virus by monoclonal antibodies against the viral surface antigen.in vitro hbv infection and neutralization were assayed using an anti-pres1 murine monoclonal antibody (1b3) and anti-pres2 (h69k) and anti-s (cs131a) murine-human chimeric antibodies. the 1b3 (igg1) and h69k (igg1) was constructed previously and the cs131a was constructed for this study by expressing stably the chimeric heavy and light chains in chinese hamster ovary cells and purifying from the culture supernatant. previous study showed that the h69k and cs131a recognize known virus-neutralizin ...19979179773
woodchuck hepatitis virus-induced carcinoma as a relevant natural model for therapy of human hepatoma.eastern american woodchuck (marmota monax), naturally infected with woodchuck hepatitis virus, a virus similar to human hepatitis b virus, develops liver cancer with a high prevalence.19979210620
threat to humans from virus infections of non-human primates.several hundred distinct non human primate species are recognised, and they are likely to harbour a similar range of viruses to humans. simians such as cynomolgus and rhesus macaques, african green monkeys, and marmosets are widely used for biomedical research, but despite this extensive close contact very few simian viruses have been shown to pose a threat of infection or illness to humans. herpesvirus simiae is the best recognised zoonotic hazard of simians. it is an alphaherpes virus of asiat ...199710398488
cloning and characterization of partial cdnas for woodchuck cytokines and cd3epsilon with applications for the detection of rna expression in tissues by rt-pcr assay.immunologic reagents and methodology are essential to develop further the woodchuck and woodchuck hepatitis virus (whv) as a model of immune response, inflammation, and immunotherapy in hepatitis b virus (hbv) infection. partial cdna clones for the woodchuck cd3epsilon marker of t cells (536 bp) and for selected woodchuck cytokines were developed, including il-1beta (332 bp), il-2 (249 bp), il-4 (205 bp), il-10 (476 bp), ifn-gamma (476 bp), and tnf-alpha (381 bp). this panel of markers includes ...19979298738
in vivo antiviral activity and pharmacokinetics of (-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in woodchuck hepatitis virus-infected woodchucks.the (-) enantiomer of cis-5-fluoro-1l-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine [(-)-ftc)], a substituted oxathiolane compound with anti-hepatitis b virus activity in vitro, was assessed for its efficacy in woodchucks with naturally acquired woodchuck hepatitis virus (whv) infection. pharmacokinetics and in vitro anabolism were also determined. (-)-ftc was anabolized to the 5'-triphosphate in a dose-related fashion, reaching a maximum concentration at about 24 h in cultured woodchuck hepat ...19979333028
therapeutic vaccination of woodchucks against chronic woodchuck hepatitis virus infection.therapeutic vaccination is a new approach to treat patients with chronic hepatitis b virus infection. we have used the woodchuck model to examine the efficacy and safety of this approach.19979365049
[efficacy of interferon alpha in primary prevention of preneoplastic lesions in a transgenic murine model of hepatocellular carcinoma related to the interaction between woodchuck hepatitis viruses and c-myc oncogene].c-myc oncogene overexpression by near insertion of hepatitis b virus is important in woodchuck hepatocarcinogenesis. this dna fragment was transferred in mice who developed hepatocellular carcinoma via preneoplastic lesions. in the present study, we tested the preventive effect of alpha interferon on the incidence of hepatocyte dysplasia.19979295972
a short linear sequence in the pre-s domain of the large hepatitis b virus envelope protein required for virion formation.envelopment of the hepatitis b virus (hbv) nucleocapsid depends on the large envelope protein l, which is expressed as a transmembrane polypeptide at the endoplasmic reticulum membrane. previous studies demonstrated that the cytosolic exposure of the n-terminal pre-s domain (174 amino acids) of l was required for virion formation. n-terminal truncations of l up to arg 103 were tolerated. to map sites in the remaining c-terminal part of pre-s important for virion morphogenesis, a series of 11 l m ...19979371594
metabolic activation of aflatoxin b1 to aflatoxin b1-8,9-epoxide in woodchucks undergoing chronic active hepatitis.chronic hepatitis b virus infection as well as consumption of food contaminated with the mycotoxin aflatoxin b1 are considered to be 2 major risk factors for the development of primary liver cancer in humans. furthermore, epidemiological surveys indicate that hepatitis b virus and aflatoxin b1 might act synergistically to induce primary liver cancer. in the present study, we have tested the hypothesis that the metabolic activation of aflatoxin b1 to aflatoxin b1-8,9-epoxide, the ultimate mutagen ...19979389576
plasma antioxidant vitamins, chronic hepatitis b virus infection and urinary aflatoxin b1-dna adducts in healthy males.epidemiological evidence indicates that aflatoxin b1 (afb1) intake is associated with an increased risk of hepatocellular carcinoma (hcc). the hepatocarcinogenesis is initiated by covalent binding of afb1 to cellular dna. to determine whether nutritional factors and hormonal status may influence the binding of afb1 to hepatic dna, a cross-sectional study was performed on a total of 42 male asymptomatic hepatitis b surface antigen (hbsag) carriers and 43 male non-carriers in a cohort study on the ...19979214602
effects of a frequent double-nucleotide basal core promoter mutation and its putative single-nucleotide precursor mutations on hepatitis b virus gene expression and replication.the basal core promoter (bcp) of hepatitis b virus (hbv) directs the transcription of both precore rna and core rna which code for e antigen (hbeag) and core antigen, respectively. a double mutation in the bcp which converts nucleotide (nt) 1762 from a to t and nt 1764 from g to a is frequently observed in patients with chronic hepatitis b. we recently demonstrated that this double mutation prevented the binding of a liver-enriched factor (lef) to the bcp, suppressed only precore rna transcripti ...19979267007
cross-reactive cellular immune responses in chickens vaccinated with live infectious bronchitis virus vaccine.two-week-old chickens were vaccinated intra-nasally with a live infectious bronchitis virus (ibv) vaccine (h120). on days 4, 7, 11 and 14 post-vaccination (p.v.) spleen mononuclear cells (mnc) prepared from control and vaccinated chickens were stimulated in vitro with homologous (strain m41) and heterologous (strains 7 and 793/b) virus antigens. antigen-specific lymphoproliferation and interleukin-2 (il-2) and interferon-y (ifn) production were used to measure cross-reactive cell mediated immune ...199718483933
[in vitro expression of wild type and precore mutant woodchuck hepatitis virus].hepatitis b virus (hbv) precore 1896 and 1898 g-->a mutations are regarded as hot spots to study. such mutants have been considered associating with molecular and biological changes of hbv and causing chronic hepatitis and severe forms of hepatitis, including fulminant hepatitis. using oligonucleotide-directed mutagenesis, we have conducted the same point mutations in the precore gene of an infectious clone of woodchuck hepatitis virus (whv-8). transfection of mutant whv dna, 1896 mutant (whv-m1 ...199715619810
efficient and inducible production of human interleukin 6 in chinese hamster ovary cells using a novel expression system.high level and inducible production of human interleukin 6 (hil-6) was achieved using a novel expression system in chinese hamster ovary (cho) cells. in this system, the transcription of hil-6 gene under the control of phcmv*-1 promoter composed of tetracycline operator sequences and a minimal promoter is activated by a chimeric transactivator (tta) composed of tetracycline repressor and transactivating domain of vp16 protein of herpes simplex virus. the transcription of tta gene, which is also ...199722358879
effects of social reorganization on cellular immunity in male cynomolgus monkeys.exposure to acute stressors has been shown to impair cellular immunity in human beings and other animal species. comparatively little is known, however, about the effects of long-term stressors on immune function and how individual behavioral characteristics may mediate differences in immune function and clinical disease susceptibility. to determine the effects of social stress on cellular immunity and reactivation of a latent herpesvirus, 20 herpes b virus-positive male cynomolgus monkeys were ...199631918506
hepatitis b virus infection of tupaia hepatocytes in vitro and in vivo.for the systematic analysis of various clinical and molecular aspects of hepatitis b virus (hbv) infection, an experimental small animal system of hbv infection would be a great advance. the susceptibility to hbv infection, therefore, of hepatocytes from the tree shrew species tupaia belangeri was studied in vitro and in vivo. primary hepatocytes isolated from livers of tupaias can be reproducibly infected with hbv. in vitro infection results in viral dna and rna synthesis in hepatocytes and sec ...19968707245
pharmacokinetics of (-)-beta-d-2-aminopurine dioxolane and (-)-beta-d-2-amino-6-chloropurine dioxolane and their antiviral metabolite (-)-beta-d-dioxolane guanine in rhesus monkeys.(-)-beta-d-2-aminopurine dioxolane (apd) and (-)-beta-d-2-amino-6-chloropurine dioxolane (acpd) are recently synthesized dioxolanylpurine nucleoside derivatives being developed as potential prodrugs for the antiviral nucleoside analog (-)-beta-d-dioxolane guanine (dxg). in vitro, apd and acpd are converted to dxg by xanthine oxidase and adenosine deaminase, respectively. the purpose of this study was to evaluate the preclinical pharmacokinetics of apd and acpd and their potential for generating ...19968891140
pharmacokinetics of (-)-2'-3'-dideoxy-3'-thiacytidine in woodchucks.the woodchuck (marmota monax) has proven to be a suitable animal model for studying hepatitis b virus (hbv) infection owing to similarities in the course of infection between woodchuck hepatitis virus (whv) in woodchucks and hbv in humans. (-)-beta-l-2',3'-dideoxy-3'-thiacytidine (3tc; lamivudine) is a nucleoside analog which has demonstrated antiviral activity against hbv as well as human immunodeficiency virus (hiv). the purpose of the present investigation was to characterize the pharmacokine ...19968851586
treatment of woodchuck hepatitis virus infection in vivo with 2', -3'-dideoxycytidine (ddc) and 2',-3'-dideoxycytidine monophosphate coupled to lactosaminated human serum albumin (l-hsa ddcmp).dideoxycytidine (ddc) is a nucleoside analogue active against human immunodeficiency virus and with in vitro activity against human hepatitis b virus. we investigated the ability of ddc to inhibit one of the hepadnaviridae, the woodchuck hepatitis virus and compared the results with the effect obtained by a conjugate of lactosaminated human serum albumin 2',-3'-dideoxycytidine monophosphate (l-hsa ddcmp). this compound specifically enters the hepatocyte via the asialoglycoprotein receptor. we tr ...19968740840
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