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identification of factor-binding sites in the duck hepatitis b virus enhancer and in vivo effects of enhancer mutations.hepatitis b viruses (hepadnaviruses) can cause chronic, productive infections of hepatocytes. analyses of the enhancers and promoters of these viruses in cell lines have suggested a requirement of these elements for liver-enriched transcription factors. in this study, a minimum of seven factor-binding sites on the duck hepatitis b virus enhancer were detected by dnase i footprinting using duck liver nuclear extracts. among the sites that were tentatively identified were one c/ebp-, one hnf1-, an ...19948139013
state of the p53 gene in hepatocellular carcinomas of ground squirrels and woodchucks with past and ongoing infection with hepadnaviruses.infection with hepadnaviruses and exposure to dietary aflatoxin are considered major risk factors in the development of hepatocellular carcinoma (hcc) both in humans and in animals. recently, a broad range of mutations in the p53 tumor suppressor gene has been reported in human hccs, predominantly from hepatitis b virus carriers in areas with either high or low levels of exposure to dietary aflatoxin. to determine whether p53 mutations are common to hccs of hosts infected with related hepadnavir ...19947923176
the woodchuck: an animal model for hepatitis b virus infection in man.since the discovery of woodchuck hepatitis virus (whv) in 1978, the virus and its host, the american woodchuck, have been studied and used as the most suitable model for human hepatitis b virus infection. whv is closely related to the human virus, having strong similarities in morphology, genome structure and gene products, replication, epidemiology, the course of infection and in the development of illness and hepatocellular carcinoma. because of this high homology, the woodchuck model is used ...19958666518
behavioral management of specific pathogen-free rhesus macaques: group formation, reproduction, and parental competence.breeding colonies of specific pathogen-free (spf) rhesus macaques were established to eradicate the transmission of herpesvirus simiae and several retroviruses in this species. strategies to attain this goal included the combination of large numbers of monkeys into groups, the establishment of small unimale groups, and a program using animals that were temporarily socially restricted. all methods required the establishment of new social groups from unfamiliar animals. in using these methods, we ...19947933968
characterization of the antiviral effects of 2' carbodeoxyguanosine in ducks chronically infected with duck hepatitis b virus.this study was carried out to evaluate benefits and limitations of long-term therapy of hepatitis b virus infections with a nucleoside analog inhibitor of virus replication. the model we used was the domestic duck chronically infected with duck hepatitis b virus by in ovo infection. 2' carbodeoxyguanosine was used as an inhibitor of viral dna synthesis. in all animals examined there was a reduction in virus production during therapy. a dose of 2' carbodeoxyguanosine of 10 micrograms/kg every oth ...19948294097
immunization with recombinant woodchuck hepatitis virus nucleocapsid antigen or hepatitis b virus nucleocapsid antigen protects woodchucks from woodchuck hepatitis virus infection.woodchucks were immunized with recombinant woodchuck hepatitis virus (whv) nucleocapsid antigen (whcag) or hepatitis b virus (hbv) nucleocapsid antigen (hbcag) and challenged with 10(6) whv id50. six out of six woodchucks immunized with whcag and four out of six immunized with hbcag were protected from whv infection. woodchucks immunized with whcag or hbcag developed high serum antibody titres against whcag or hbcag. antibodies against whc and hbc displayed little cross-reactivity (< 1%). this c ...19938322485
reactogenicity and immunogenicity of a new recombinant hepatitis b vaccine containing pre s antigens: a preliminary report.a new vaccine against hepatitis b virus (hbv) infection, produced in mammalian chinese hamster ovary (cho) cells, contains the small(s), middle (pre s2) and large (pre s1) surface proteins of hbv. three injections of a 5-micrograms or 10-micrograms dose were administered intramuscularly (i.m.) at 0, 1 and 6 months to a group of 105 young adults, who were monitored for a period of 6 months after the third injection. seroconversion rates were 100% after the second injection of the 5-micrograms or ...19968736239
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
activation of n-myc2 gene expression by cis-acting elements of oncogenic hepadnaviral genomes: key role of enhancer ii.woodchuck hepatitis virus (whv) is strongly oncogenic in its native host, producing hepatocellular carcinomas in the majority of chronically infected animals. an important step in this oncogenic process is the activation of n-myc transcription in the liver as a result of integration of viral sequences in cis to the n-myc2 locus. we have examined the viral sequences involved in the up-regulation of n-myc2 using transient transfection assays of permissive hepg2 cells in culture. whv sequences corr ...19968599232
species specificity for hbsag binding protein endonexin ii.hepatitis b virus displays a distinct species and tissue tropism. previously we have demonstrated that a human liver plasma membrane protein with a molecular weight of approximately 34 kilodalton specifically binds to hbsag. this protein was identified as endonexin ii, a ca2+ dependent phospholipid binding protein.19968778191
therapeutic basis of glycyrrhizin on chronic hepatitis b.glycyrrhizin, a major component of a herb (licorice), has been intravenously used for the treatment of chronic hepatitis b in japan and improves liver function with occasional complete recovery from hepatitis. this substance modifies the intracellular transport and suppresses sialylation of hepatitis b virus (hbv) surface antigen (hbsag) in vitro. this study was designed to clarify the pharmacological basis for its effectiveness. the structure-bioactivity relationship of glycyrrhizin, glycyrrhet ...19968783808
[production of transgenic rabbits by micro injection].the feasibility of using whole animal instead of bioreactor in genetic engineering has been investigated with transgenic domestic rabbits. the gene chosen is the surface gene (s gene) of hepatitis b virus. two plasmids were specifically constructed for this purpose, phbv3.0 contains the promoter pre s gene and a part of c gene of the virus; while mt-sa, the s gene and mouse mt promotor. these plasmids were made linear by suitable restriction endonuclease before they were transferred into malepro ...19938329213
2',3'-dideoxy-3'-fluoroguanosine inhibits duck hepatitis b virus in vivo.duck hepatitis b virus (dhbv) belongs to the same virus family as the human hepatitis b virus (hbv). domestic ducks infected with dhbv can be used as an animal model for chronic hepatitis b virus infection in therapeutic trials. in this study the antiviral effect of the guanosine analogue 2',3'-dideoxy-3'-fluoroguanosine (flg) was tried in vivo on chronically dhbv-infected ducks. the ducks were either congenitally infected, or inoculated with dhbv immediately post-hatch. flg was given as intrape ...19968811639
unique pres sequence in a gibbon-derived hepatitis b virus variant.a unique hepatitis b virus (hbv) variant has been identified in a gibbon (hylobates lar) which could be passed to a chimpanzee by experimental inoculation. this hbv variant had been shown to have no reactivity to a monoclonal anti-pres2 antibody (pres2 mab 116-34) differentiating it from all human hbv specimens tested. this gibbon sera also was not recognized by an anti-pres1 mab which binds the pres1 hepatocyte receptor region, amino acids 27-35. in this paper, we report the dna sequence of the ...19938363598
safety of 9-(2-phosphonylmethoxyethyl)adenine (pmea) in patients with human immunodeficiency virus infection: a pilot study.the compound 9-(2-phosphonylmethoxyethyl)adenine (pmea) is a potent inhibitor of a number of viruses in vitro such as human immunodeficiency virus types 1 and 2, herpes simplex virus types 1 and 2, hepatitis b virus, cytomegalovirus, and epstein-barr virus. pmea also proved to be effective in vivo against feline immunodeficiency virus in cats and simian immunodeficiency virus in rhesus monkeys. in an open, non-placebo-controlled trial, the safety of weekly doses of pmea in 10 patients with acqui ...19968861829
human hepatitis b virus and hepatocellular carcinoma. i. experimental infection of tree shrews with hepatitis b virus.tree shrews (tupaia belangeri chinenesis) can be experimentally infected with human hepatitis b virus (hbv) by inoculation with human serum positive for hbv, the experimental infection rate being 55.21%. successive infections have been passed through five generations among the tree shrews inoculated with hbv-positive sera from the infected animals, the average infection rate being 94.0%. the experimental infection of tree shrews with hbv may be prevented by immunization with hepatitis b vaccine, ...19968609151
use of dominant negative mutants of the hepadnaviral core protein as antiviral agents.chronic hepatitis b virus (hbv) infection is a major cause of acute and chronic liver diseases. we have recently described hbv and woodchuck hepatitis virus (whv) dominant negative (dn) core mutants that were capable of inhibiting wild-type viral replication by 95%. these mutants may represent a potent class of antiviral agents that act as "intracellular immunogens." to facilitate their potential use in animal model systems, we now have studied the duck hbv (dhbv) and placed the dn mutant constr ...19968903368
[preparation and study of recombinant strains of venezuelan equine encephalomyelitis virus expressing the pres2-s gene of the hepatitis b virus].venezuelan equine encephalomyelitis (vee) virus-based vectors for expression of heterologous genes have been constructed using full-length cdna copy of the interstrain recombinant virus (trinidad donkey and 230 strain). gene cassettes carrying the subgenomic mrna promoter of vee virus and the pres2-s gene of hepatitis b virus (hbv) were inserted before or after the genes of structural viral proteins. live virus stocks were obtained by transfection of chick embryo fibroblasts with in vitro transc ...19968928499
human hepatitis b virus and hepatocellular carcinoma. ii. experimental induction of hepatocellular carcinoma in tree shrews exposed to hepatitis b virus and aflatoxin b1.on the basis of the successful establishment of an animal model in tree shrews experimentally infected with human hepatitis b virus (hbv), a study on the hepatocarcinogenic effects of hbv and/or aflatoxin b1 (afb1) was conducted. the results showed that the incidence of hepatocellular carcinoma (hcc) was significantly higher in the animals both infected with hbv and exposed to afb1 (52.94%) than in those solely infected with hbv (11.11%) or exposed to afb1 (12.50%). no hcc of precancerous lesion ...19968609152
liver-targeted antiviral nucleosides: enhanced antiviral activity of phosphatidyl-dideoxyguanosine versus dideoxyguanosine in woodchuck hepatitis virus infection in vivo.it would be desirable to develop antiviral agents that can be targeted to liver to enhance their antiviral effects and reduce nonhepatic toxicity. 2',3'-dideoxyguanosine (ddg) has been found to be a potent and selective antihepatitis b agent both in vitro and in vivo. to evaluate ddg and its liver-targeted analog, we synthesized a series of phosphatidyl-ddgs and incubated them with 2.2.15 cells, which chronically produce hepatitis b virus. 1,2-dipalmitoylphosphatidyl-dideoxyguanosine (dpp-ddg) i ...19968621175
a hepatitis b virus pre-s-retinoic acid receptor beta chimera transforms erythrocytic progenitor cells in vitro.in this report, we investigated the transforming properties of retinoic acid receptor beta (rar beta). the v-erba protein, which is the viral oncogenic homologue of the thyroid hormone receptor, was replaced by either the complete rar beta (beta r) or a hepatitis b virus pre-s-rar beta (h beta r) hybrid product in an avian erythroblastosis virus-based vector. in chicken hematopoietic cells, the h beta r protein was able to transform erythroid progenitor cells, whereas no such transformation was ...19938093562
a functional n-myc2 retroposon in ground squirrels: implications for hepadnavirus-associated carcinogenesis.three hepatitis b viruses infecting humans, woodchucks and ground squirrels increase the risk of hepatocellular carcinoma in their respective hosts. the woodchuck hepatitis b virus (whv), unlike the two other viruses, induces a rapid carcinogenic process characterized by direct activation of myc proto-oncogenes by insertion of viral dna. the highly preferred target of insertional mutagenesis in woodchucks is n-myc2, an intronless n-myc gene. strikingly, n-myc2 has no human homolog and the homolo ...19968649862
influenza b virus nb glycoprotein is a component of the virion.the influenza b virus nb glycoprotein is abundantly expressed at the surface of virus-infected cells. nb spans the membrane once and has an 18 amino acid ectodomain, a 22 amino acid transmembrane domain, and a 60 amino acid cytoplasmic tail. the nb n-terminal ectodomain contains two asparagine residues that are modified by the addition of palmitic n-linked carbohydrate chains, which become further modified by the addition of polylactosaminoglycan. we have now shown that nb is also modified by ad ...19968661386
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
characterization and biosynthesis of the woodchuck hepatitis virus e antigen.the biosynthesis of the secretory core gene product of the woodchuck hepatitis virus (whv) was studied in human cells. we have shown that the whv e antigen was a n-glycosylated (most likely a diglycosylated) protein, with an apparent m(r) of 24k. to demonstrate that the whv precore protein was correctly processed in human cells, we engineered chimeric proteins in which signal peptides or arginine-rich domains of whv and hepatitis b virus (hbv) precore proteins were exchanged. our results showed ...19948113724
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
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
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
epidemiology of cercopithecine herpesvirus 1 (b virus) infection and shedding in a large breeding cohort of rhesus macaques.the epidemiology of b virus infection in a large (n = 157) cohort of rhesus macaques at the california regional primate research center was evaluated prospectively from september 1989 through january 1991 by serial physical examinations, a behavioral substudy (n = 51), and repeated diagnostic testing. half were b virus antibody-positive at baseline; subsequently, incident cases of infection were documented through serology alone (42) or with virus isolation (5). eight recurrent infections and a ...19938380607
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
overexpression of a p-glycoprotein in hepatocellular carcinomas from woodchuck hepatitis virus-infected woodchucks (marmota monax).the leading cause of human hepatocellular carcinomas (hccs) is hepatitis b virus (hbv) infection. woodchucks infected with a closely related hepadnavirus, woodchuck hepatitis virus (whv), serve as a model for hbv because woodchucks chronically infected with whv also develop hepatocellular carcinomas. increased expression of p-glycoprotein (pgp) in human hccs is a common obstacle in successful cancer chemotherapy. pgps are encoded by a family of multidrug-resistance (mdr) genes. livers from uninf ...19968666315
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
[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
the in vitro anti-hepatitis b virus activity of fiau [1-(2'-deoxy-2'-fluoro-1-beta-d-arabinofuranosyl-5-iodo)uracil] is selective, reversible, and determined, at least in part, by the host cell.a human hepatoblastoma cell line was stably transfected with a head-to-tail dimer of the hepatitis b virus (hbv), subtype adw, genome to generate a cell line which produces hbv. fiau [1-(2'-deoxy-2'-fluoro-1-beta-d-arabinofuranosyl-5-iodo)uracil] inhibited viral replication in these cells with an ic50 of 0.90 microm, as determined by pcr analysis of extracellular dane particle dna, and displayed a 50% cytotoxic concentration (tc50) of 344.3 microm, as determined using the mtt assay. the selectiv ...19948141592
different in situ expression of insulin-like growth factor type ii in hepatocellular carcinoma. an in situ hybridization and immunohistochemical study.reexpression of the insulin-like growth factor type ii (igf-ii) gene has recently been described in hepatocellular carcinoma (hcc). in this study, we used a nonisotopic in situ hybridization method to analyze the expression of igf-ii mrna in a series of 28 hccs arising on cirrhotic and noncirrhotic livers. an immunohistochemical method was used to detect igf-ii peptide. hepatitis b virus (hbv) status and the histological differentiation degree were also evaluated. increased expression of igf-ii ...19948162257
[recombinant oka varicella vaccine as a live hepatitis b virus vaccine].recombinant oka varicella-hepatitis b virus (hbv) vaccine was constructed by inserting the hbv surface antigen (hbsag) gene coding partial pres2 and whole s regions into the viral thymidine kinase gene. hbsag was expressed in the cytoplasm of infected cells. intracellular hbsag (26k and 30k) was n- and o-glycosylated, sialylated, and secreted into the supernatant as 30k and 35k hbsag particles. recombinant virus induced antibody response to both varicella-zoster virus and hbsag in guinea pigs an ...19938381884
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
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
molecular events in the pathogenesis of hepadnavirus-associated hepatocellular carcinoma.chronic hepadnavirus infection is associated with hepatocellular carcinoma (hcc) in natural hosts such as humans, woodchucks, and beechey ground squirrels. several possible oncogenic mechanisms have been identified, including a potential role of the hepadnavirus x (hbx) gene, which transactivates transcription regulated by certain cis-acting sequences, e.g. regulatory sequences of the hepatitis b virus (hbv) and heterologous regulatory sequences of other viruses and cellular genes. the oncogenic ...19948198385
duck hepatitis b virus infection, aflatoxin b1 and liver cancer in ducks.the association between chronic infection by hepadnaviruses isolated from human (hbv), woodchuck (whv), ground squirrel (gshv) and development of hepatocellular carcinoma (hcc) in their respective hosts is well established (reviewed in [11, 15, 17]). by contrast, the association of duck hepatitis b virus (dhbv) infection with hcc is less documented. pekin ducks congenitally infected with dhbv and followed for several years throughout the world do not develop liver tumors: hcc has been found only ...19938260880
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
direct cloning and expression of pcr amplified dna and rna sequences: application to the hepadnaviruses nucleocapsid proteins.gene amplification may benefit from the construction of primers that augments the speed at which cloning and protein expression proceeds. such primers include ecori or hindiii linkers as well as an in phase initiation or termination codon. pcr was carried out directly from viral particles of human hepatitis b virus (hbv) and woodchuck hepatitis virus (whv) without dna purification and from rna extracted from whv infected liver. amplified products were directly cloned in the pkk223-3 expression v ...19938514845
duck hepatitis b virus infection, aflatoxin b1 and liver cancer in domestic chinese ducks.the oncogenicity of duck hepatitis b virus (dhbv) is unclear since hepatocellular carcinomas (hccs) have been reported only in domestic ducks in qidong, an area of china where hepatitis b virus (hbv) and aflatoxin b1 (afb1) are risk factors for liver cancer in man. in order to better define the association between dhbv infection, afb1 and hcc we analysed a series of 16 duck liver samples collected from local farms in qidong. hcc was found in eight and cirrhosis in one of these samples. furthermo ...19948286190
liver targeting of adenine arabinoside monophosphate (ara-amp) by coupling to lactosaminated human serum albumin.adenine arabinoside monophosphate (ara-amp) is a potent antiviral agent against hepadnaviruses but its use in the treatment of chronic hepatitis b is hampered by severe neurotoxic side effects, which are dose dependent. in order to reduce these adverse reactions and to adopt the lysosomotropic approach to antiviral chemotherapy, ara-amp was coupled to lactosaminated human serum albumin (l-hsa), a neoglycoprotein which specifically penetrates hepatocytes. in mice with ectromelia virus hepatitis, ...19958520036
phosphatidyl-2',3'-dideoxy-3'-thiacytidine: synthesis and antiviral activity in hepatitis b-and hiv-1-infected cells.we recently found that phosphatidyl-2',3'-dideoxycytidine (phosphatidyl-ddc) had substantial anti-hepatitis b virus (hbv) activity in vitro compared to 2',3'-dideoxycytidine (ddc) (hostetler et al. (1994) antiviral res. 24, 59-67). upon administration of liposomal phosphatidyl-ddc to mice, a 40-fold higher drug area under curve was observed in the liver. to evaluate the possibility of using liver-targeted anti-hbv nucleosides to treat woodchuck hepatitis virus, we wanted to find the most potent ...19958585765
an animal study on transmission of hepatitis b virus through mosquitoes.three gena of mosquitoes were fed with human blood infected with hepatitis b virus (hbv) artificially. when blood in the stomach was completely digested, mosquitoes were used to bite monkeys tupaia belangeri. a month after biting, venous blood samples were taken from the monkeys to detect serum hbsag, hbeag, anti-hbs and anti-hbc. among 29 test monkeys, 9 were hbv infective serum markers positive. in 4 of 16 test monkey liver biopsies, acute inflammatory changes were found with hematoxylin-eosin ...19958728939
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
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
duck hepatitis b virus polymerase acts as a suppressor of core protein translation.nucleocapsid assembly in hepadnavirus replication requires selective encapsidation of the pregenomic rna template and the viral polymerase by the core proteins. it has been shown that an encapsidation signal located at the 5' end of the pregenomic rna is responsible for its interaction with the polymerase. in the present study, we have shown that a region located at the 3' periphery of the core open reading frame may interact with the viral polymerase in duck hepatitis b virus. by using an in vi ...19968764010
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
what is the situation of human t cell lymphotropic virus type ii (htlv-ii) in africa? origin and dissemination of genomic subtypes.human t cell lymphotropic virus type ii (htlv-ii) and its two genomic subtypes, a and b, which differ by 3 to 6% at the nucleotide level (depending on the gene studied), were until recently considered to be endemic only in certain indian tribes in the americas and were therefore considered mainly as a "new world virus." first, the evidence of htlv-ii antibodies and later characterization of isolates from sex workers or individuals living in large west and central african cities suggested that ht ...19968797728
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
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
[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
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
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
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
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
absence of mutations in the p53 tumor suppressor gene in woodchuck hepatocellular carcinomas associated with hepadnavirus infection and intake of aflatoxin b1.infection with hepadnaviruses and exposure to aflatoxin b1 (afb1) are considered major risk factors in the development of hepatocellular carcinoma (hcc) in humans and in animals. a high rate of mutations in the p53 tumor suppressor gene in hepatocellular carcinomas of predominantly hepatitis b virus (hbv) carrier patients has been recently related to dietary aflatoxin. another member of the hepadnavirus family, the woodchuck hepatitis virus (whv), infects woodchucks in a manner similar to that o ...19969006107
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
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
hepatitis b virus: specific binding and internalization of small hbsag by human hepatocytes.previously, we identified human liver endonexin ii (eii) present on human hepatocyte plasma membrane as a specific hepatitis b surface antigen (hbsag) binding protein. we also showed the spontaneous development of anti-idiotypic (anti-hbsag) antibodies in rabbits immunized with eii and in chicken immunized with the f(ab')2 fragment of rabbit anti-eii igg. these findings suggest the existence of a receptor-ligand relationship between eii and hbsag. in the present study, we demonstrate that small ...19959049356
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
covalently closed circular viral dna formed from two types of linear dna in woodchuck hepatitis virus-infected liver.we found that livers from woodchucks chronically infected with woodchuck hepatitis virus (whv) contained covalently closed circular dna (cccdna) molecules with deletions and insertions indicative of their formation from linear viral dna by nonhomologous recombination, as we previously described for the duck hepatitis b virus (w. yang and j. summers, j. virol. 69:4029-4036, 1995). however, evidence for two different types of linear precursors was obtained by analysis of the recombination joints i ...19968676483
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
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
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
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
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
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
[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
[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
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
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
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
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
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
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