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woodchuck hepatitis virus surface antigen produced in vitro fails to bind polymerized woodchuck serum albumin.using a plasmid (psws) similar to one that has been successfully used for large-scale production of hepatitis b virus (hbv) envelope protein particles (psvs) but containing the corresponding woodchuck hepatitis virus (whv) envelope gene sequences, we have stably transformed the rodent dihydrofolate reductase-deficient cell line cho dhfr-. although production of whv envelope particles in cho/psws cell lines was low, it was sufficient to test whether these particles could bind to polymerized serum ...19948046413
apparent helper-independent infection of woodchucks by hepatitis delta virus and subsequent rescue with woodchuck hepatitis virus.hepatitis delta virus (hdv) is a subviral agent of humans which is dependent upon hepatitis b virus as a helper for transmission. hdv can be experimentally transmitted to woodchucks by using woodchuck hepatitis virus (whv) as the helper. we used this model system to study two types of hdv infections: those of animals already chronically infected with whv and those of animals without any evidence of prior exposure to whv. at 5 to 10 days after infection with hdv, liver biopsies of these two group ...19948057418
dot blot hybridization assay for the detection of duck hepatitis b virus dna among healthy indian country ducks.a dna molecular hybridization technique employing duck hepatitis b virus (dhbv) dna of 3.0 kilobase pairs as a probe was used to screen for the presence of dhbv dna in blood samples, collected from 90 apparently healthy indian country ducks. six out of 90 ducks showed positivity for dhbv dna in serum (5.4%) and only 4 out of 6 dhbv dna positive ducks answered in counter immuno electrophoresis (ciep) using specific antibody against dhbv surface antigen raised in guinea pig. the results indicate t ...19948088900
pure nucleoside enantiomers of beta-2',3'-dideoxycytidine analogs are selective inhibitors of hepatitis b virus in vitro.(-)-beta-l-2',3'-dideoxycytidine (beta-l-ddc), (+)-beta-d-2',3'-dideoxycytidine (beta-d-ddc), (-)-beta-l-2',3'-dideoxy-5-fluorocytidine (beta-l-fddc), (-)-beta-l-2',3'-dideoxy-5-fluoro-3'-thiacytidine (beta-l-ftc), and (+)-beta-d-1,3-dioxolane-5-fluorocytidine (beta-d-fdoc) were evaluated for their anti-hepatitis b virus (anti-hbv) activities in hbv-transfected human liver cells (2.2.15). the order of decreasing potency for the compounds at the 90% effect level was beta-d-fdoc > beta-l-ftc > bet ...19947811039
pharmacokinetics, oral bioavailability, and metabolism in mice and cynomolgus monkeys of (2'r,5's-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine, an agent active against human immunodeficiency virus and human hepatitis b virus.(2'r,5's-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine (524w91) is a nucleoside analog with potent anti-human immunodeficiency virus and anti-human hepatitis b virus activities in vitro. the pharmacokinetics and bioavailability of 524w91 after oral dosing were studied in mice dosed with 10, 100, and 600 mg of 524w91 per kg of body weight by the oral and intravenous routes. cynomolgus monkeys were dosed with 10 and 80 mg of 524w91 per kg. in both species, the clearance of 524w ...19947695253
duck hepatitis b virus infection of muscovy duck hepatocytes and nature of virus resistance in vivo.to test the hypothesis that in vivo resistance to hepadnavirus infection was due to resistance of host hepatocytes, we isolated hepatocytes from muscovy ducklings and chickens, birds that have been shown to be resistant to duck hepatitis b virus (dhbv) infection, and attempted to infect them in vitro with virus from congenitally infected pekin ducks. chicken hepatocytes were resistant to infection, but we were able to infect approximately 1% of muscovy duck hepatocytes in culture. infection requ ...19947511172
distinguishing between acute and symptomatic chronic hepatitis b virus infection.differentiating between an acute hepatitis b (ah-b) infection and an acute exacerbation of a chronic hepatitis b (ch-b) infection can present a problem for the clinician. the only current serological method of distinguishing between acute and symptomatic chronic hepatitis b virus (hbv) infection is the immunoglobulin m antibody to hepatitis b core antigen (anti-hbc) assay, which can be problematic. therefore, in an attempt to better distinguish between acute and chronic hbv infection, sera from ...19947511551
replication of influenza b virus in chicken embryos is suppressed by exogenous aprotinin.chicken embryo proteinases, one of which is a blood clotting factor xa-like proteinase, are known to effectively cleave the haemagglutinin (ha) of influenza b viruses to permit their replication in chicken embryonated eggs. here we show that injection of the serine proteinase inhibitor, aprotinin, into the allantoic cavity of eggs infected with influenza b/hong kong/73 and b/lee/40 viruses suppresses the viral ha cleavage and reduces the virus proteolytic activation and replication. effective in ...19947515225
thf gamma 2 stimulates cytokine release by peripheral blood mononuclear cells of patients with chronic hepatitis b virus infection.a recent study indicated that thymic hormones have antiviral effects in human hepatitis b virus infection and woodchuck hepatitis virus infection. these hormones are known to exert immunomodulatory effects on lymphocyte maturation and function; because these are abnormal in patients with chronic hepatitis b virus infection, we have examined the effects of a thymic hormone (thf gamma 2) on peripheral blood mononuclear cells from patients with chronic hepatitis b virus infection. thf gamma 2 (50 o ...19947516950
phenotypic mixing between different hepadnavirus nucleocapsid proteins reveals c protein dimerization to be cis preferential.hepadnaviruses encode a single core (c) protein which assembles into a nucleocapsid containing the polymerase (p) protein and pregenomic rna during viral replication in hepatocytes. we examined the ability of heterologous hepadnavirus c proteins to cross-oligomerize. using a two-hybrid assay in hepg2 cells, we observed cross-oligomerization among the core proteins from hepatitis b virus (hbv), woodchuck hepatitis virus, and ground squirrel hepatitis virus. when expressed in xenopus oocytes, in w ...19947518533
improved immunogenicity in mice of a mammalian cell-derived recombinant hepatitis b vaccine containing pre-s1 and pre-s2 antigens as compared with conventional yeast-derived vaccines.the widely used hepatitis b virus (hbv) vaccines consist of the small hepatitis b surface (shbs) protein produced in transfected yeast cells. the frequency of non-responders, especially among immunocompromised patients, has increased the demand for a more immunogenic vaccine. we evaluated the immunogenicity of recombinant hbs 20 nm particles secreted by transfected chinese hamster ovary (cho) cells, bio-hep-b (biotechnology general ltd, israel), and compared it with yeast-derived vaccines. the c ...19947533967
cytosolic activation of aromatic and heterocyclic amines. inhibition by dicoumarol and enhancement in viral hepatitis b.the aromatic amines 2-aminofluorene (2af), 2-acetylaminofluorene, and 2-aminoanthracene, and the heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (iq), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, and 3-amino-1-methyl-sh-pyrido[4,3-b]indole (trp-p-2) were activated by rat liver cytosolic fractions to form mutagenic metabolites in salmonella typhimurium strains ta98, ta98nr, and ta98/1,8-dnp6. in the case of the trp-p-2, the cytosolic activation was even more potent than the microsomal ...19947534225
detection of an rnase h activity associated with hepadnaviruses.replication of the hepadnavirus dna genome is accomplished via reverse transcription of an intermediate, pregenomic rna molecule. this process is likely to be carried out by a virally encoded, multifunctional polymerase which possesses dna- and rna-dependent dna polymerase and rnase h activities. however, the nature of the product(s) of the polymerase gene predicted to mediate these functions is unclear. biochemical studies of the polymerase protein(s) have been limited by its apparent low abund ...19957543585
in vitro activation of woodchuck lymphocytes measured by radiopurine incorporation and interleukin-2 production: implications for modeling immunity and therapy in hepatitis b virus infection.cellular immune responses to hepatitis b virus (hbv) play an important role in the resolution of acute infection. they also influence the course of chronic infection and disease but are inadequate to completely clear the infection. woodchuck hepatitis virus (whv) infection of the woodchuck can provide a model to study these processes. lymphocyte responses of woodchucks were assessed by in vitro proliferation and/or interleukin (il)-2 assays using mitogen (concanavalin a [cona]), cytokine (il-2), ...19957544755
inhibition of woodchuck hepatitis virus replication by adenine arabinoside monophosphate coupled to lactosaminated poly-l-lysine and administered by intramuscular route.we prepared a hepatotropic conjugate, suitable for intramuscular (im) injection, of lactosaminated poly-l-lysine with adenine arabinoside monophosphate (ara-amp), a drug active against hepatitis b virus (hbv). we studied its organ distribution in mice and its antiviral activity in woodchucks that are carriers of woodchuck hepatitis virus (whv). in mice, after im administration of a conjugate tritiated in the drug moiety (5.2 micrograms/g equal to 2 micrograms/g of ara-amp) radioactivity in liver ...19957557853
complete nucleotide sequence of the herpesvirus simiae glycoprotein g gene and its expression as an immunogenic fusion protein in bacteria.the nucleotide sequence of a 2384 bp portion within the unique short (us) region of the herpesvirus simiae (simian herpes b virus; shbv) genome is presented. a partial and a complete open reading frame (orf) were found within this nucleotide sequence. the partial orf encodes the c terminus (147 amino acids) of a protein kinase which is highly conserved in the herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) and simian agent 8 (sa8) us regions. the complete orf is located 3' to the partial ...19957561753
recombinant duck interferon: a new reagent for studying the mode of interferon action against hepatitis b virus.although interferon is widely used to treat chronic hepatitis b virus infections, its mode of action against hepadnaviruses is largely unknown. this deficit is due mainly to the lack of suitable model systems. the duck system could not be used because purified duck interferon was not available in sufficient quantities. we have now cloned a dna fragment that contains an intronless gene for duck interferon. the primary translation product consists of 191 amino acids, the n-terminal 30 residues of ...19957571434
transactivation of cellular gene expression by hepatitis b viral proteins: a possible molecular mechanism of hepatocarcinogenesis.epidemiologic data indicate the crucial role of chronic hepatitis b virus (hbv) infection in hepatocellular carcinoma (hcc) development. on the molecular level, hbv sequences are frequently integrated in hepatocellular dna. however, in contrast to the woodchuck model, in which specific hbv-dna integration is detectable in most cases, insertional (in-) activation of cellular genes seems to be a rare event in man. the recent discovery of transactivating functions exerted by hbx and truncated hbs(u ...19957602073
evaluation of tuberculin testing and measles prophylaxis procedures used in rhesus macaque quarantine/conditioning protocols.twenty-three of 103 adult rhesus macaques (macaca mulatta) entering nih holding facilities with no history of measles vaccination or infection, no titer to rubeola virus, a minimum of four negative results of intrapalpebral tuberculosis tests, and negative for herpesvirus simiae and type d retroviruses were selected to evaluate the adequacy of commonly used quarantine/conditioning protocol procedures. one month after sensitization by subcutaneous inoculation with 100 mg of killed mycobacterium t ...19957603012
susceptibility to duck hepatitis b virus infection is associated with the presence of cell surface receptor sites that efficiently bind viral particles.to test the hypothesis that susceptibility of hepatocytes to duck hepatitis b virus (dhbv) infection requires cell surface receptors that bind the virus in a specific manner, we developed an assay for the binding of dhbv particles to monolayers of intact cells, using radiolabeled immunoglobulin g specific for dhbv envelope protein. both noninfectious dhbv surface antigen particles and infectious virions bound to a susceptible fraction (approximately 60%) of pekin duck hepatocytes. in contrast, b ...19957609048
synergistic hepatocarcinogenic effect of hepadnaviral infection and dietary aflatoxin b1 in woodchucks.interactive hepadnaviral and chemical hepatocarcinogenesis was studied in woodchucks inoculated as newborns with woodchuck hepatitis virus (whv), which is closely related to the human hepatitis b virus. when the woodchucks reached 12 months of age, aflatoxin b1 (afb1) was administered in the diet at dose levels of 40 micrograms/kg body weight/day for 4 months and subsequently 20 micrograms/kg body weight/day (5 days/week) for lifetime. whv dna was demonstrated by southern blot hybridization in t ...19957614467
efficient production of anti-(hepatitis b virus) antibodies and their neutralizing activity in chimpanzees.for industrial production of human monoclonal antibodies (hmab) against hepatitis b virus surface antigen (hbsag), we scaled-up a short-term perfusion culture in serum-free medium, which was chosen as the most suitable culture method, to a 50-1 fermentor equipped with a rotating shear filter. using hydrophobic chromatography as the initial step of hmab purification, the mab hbw4, hbw6 and w471 were isolated in good quality from the respective culture broths in yields of approximately 75%. each o ...19957632396
identification of woodchuck class i mhc antigens using monoclonal antibodies.two class i major histocompatibility complex (mhc) proteins with molecular masses of 43- and 39-kda were identified in the cell surface membranes of normal woodchucks using a newly developed antiwoodchuck class i monoclonal antibody (mab) b1b.b9 and immunoblotting. b1b.b9 was generated by immunizing mice with viable woodchuck peripheral blood mononuclear cells and was selected for anti-class i mhc reactivity using a cellular enzyme-linked immunoassay, indirect immunofluorescence on tissue sectio ...19957652741
differential gene expression in experimental hepatocellular carcinoma induced by woodchuck hepatitis b virus.hepatitis b virus infection is closely linked to hepatocellular carcinoma (hcc), the pathological mechanism of hepatocarcinogenesis by this virus is not well understood. in order to gain further insight into the molecular mechanism of hcc, we constructed and screened a subtracted c-dna library which was specific to hcc cells of a woodchuck infected with woodchuck hepatitis b virus. among eight clones that were isolated based on their differential expressions, we determined nucleotide sequences o ...19957656224
herpesvirus papio 2, an sa8-like alpha-herpesvirus of baboons.several sa8 isolates obtained from baboons were compared to the prototype sa8 herpesvirus of african green monkeys. sds-page and restriction enzyme analyses revealed definite differences between green monkey and baboon isolates. dna and amino acid sequences of the gb, gd and gj glycoprotein genes exhibited substantial differences in variable regions. for the gb and gd, the amount of amino acid substitutions between sa8 and the baboon viruses was comparable to levels observed between analogous ge ...19957733825
detection of hepatitis b and woodchuck hepatitis viral dna in plasma and mononuclear cells from heparinized blood by the polymerase chain reaction.amplification by the polymerase chain reaction (pcr) of hepatitis b virus (hbv) dna extracted from parallel samples of serum and heparinized plasma gave contradictory results, indicating that heparin inhibits virus detection. similarly, analysis of pcr products of woodchuck hepatitis virus (whv) dna showed that heparinization of blood abolished whv dna amplification, while anticoagulation with sodium edta or acid citrate dextrose did not. amplification of recombinant whv and hbv dna in the prese ...19957738148
risk of venereal b virus (cercopithecine herpesvirus 1) transmission in rhesus monkeys using molecular epidemiology.the importance of venereal modes of b virus (cercopithecine herpesvirus 1) transmission was evaluated in 49 rhesus monkeys tested at necropsy. antibodies to b virus were demonstrated in 19 monkeys, but no active viral shedding was detected in mucosal swabs collected at death. the polymerase chain reaction demonstrated presence of the icp 18.5 (ul28) gene of b virus in neuronal tissues of 15 monkeys presumed to be latently infected, including 12.8% of trigeminal and 22.9% of lumbosacral ganglia p ...19957751688
phenotypic mixing of rodent but not avian hepadnavirus surface proteins into human hepatitis b virus particles.the virus family hepadnaviridae comprises two genera: orthohepadnaviruses isolated from humans (hepatitis b virus [hbv]) and rodents (e.g., woodchuck hepatitis virus [whv]) and avihepadnaviruses isolated from birds (e.g., duck hepatitis b virus [dhbv]). they carry in their envelopes two (dhbv) or three (hbv and whv) coterminal proteins referred to as small (s), middle (m), or large (l) surface protein. these proteins are also secreted from infected cells as subviral particles consisting of surfa ...19957815496
duck hepatitis b virus integrations in lmh chicken hepatoma cells: identification and characterization of new episomally derived integrations.while the cytoplasmic phase of the hepadnavirus replication cycle is well understood, very little is known about the nuclear phase. in contrast to retroviruses, proviral integration is not required for hepadnavirus replication; however, some of the viral dnas in the nucleus are diverted into an integration pathway. under certain conditions these integrations function as carcinogenic agents. in order to study the integration process, we have utilized lmh-d2 cells, which replicate wild-type duck h ...19957494330
spectrum of liver disease and duck hepatitis b virus infection in a large series of chinese ducks with hepatocellular carcinoma.the striking difference in the geographical distribution of liver cancer in ducks raised the question of whether duck hepatitis b virus (dhbv), like mammalian hepadnaviruses, could be an oncogenic agent. hepatocellular carcinomas (hccs) have been found only in domestic ducks in qidong, china, where hepatitis b virus infection and aflatoxin b1 (afb1) are both risk factors and where a high frequency of human hccs has been reported. to date, the study of liver pathology occurring in chinese ducks h ...19957768491
[induction of protective immune responses by a chimeric soluble protein from a recombinant bcg vector candidate vaccine to hiv-1].we have been isolated hiv strains from blood specimens of hiv infected individuals in japan for these 6 years. the number of specimens tested reached approximately 1,700 that ninety percent of them were from hemophiliacs repeatedly injected blood products from the united states. more than 300 of field hiv were successfully isolated from the samples. the isolation rates has decreased to 30 percent in 1993 from 40 percent in 1992, suggesting that treatment with anti-hiv drugs such as azt and/or dd ...19957783347
carbohydrate-dependent biological activities of glycosylated human interferon-beta on human hepatoblastoma cells in vitro.to evaluate the relationship between the sugar chain structure and biological activity, fibroblast-derived glycosylated human interferon-beta, chinese hamster ovary cell-derived glycosylated recombinant human interferon-beta and escherichia coli-derived unglycosylated recombinant human interferon-beta were evaluated using human hepatoblastoma cells in vitro. native fibroblast interferon-beta expressed more cell-growth inhibitory action, 2'5'-oligoadenylate synthetase induction, and the inhibitio ...19957783683
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
high-performance liquid chromatographic determination of (-)-beta-d-2,6-diaminopurine dioxolane and its metabolite, dioxolane guanosine, using ultraviolet and on-line radiochemical detection.(-)-beta-d-2,6-diaminopurine dioxolane (dapd) and its metabolite dioxolane guanosine (dxg) have potent activity against hepatitis b virus and hiv, in vitro. a reversed-phase hplc analytical method using uv and on-line radiochemical detection for the determination of dapd and dxg in monkey serum and urine is described in this report. retention times for dxg, dapd and internal standard (2',3'-didehydro-2'deoxythymidine, d4t) were 5.0, 6.0 and 13.0 min, respectively. the extraction recovery was gre ...19958590923
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
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
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
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
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
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
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
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
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
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
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
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
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
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
antiviral activity of a conjugate of adenine-9-beta-d-arabinofuranoside 5'-monophosphate and a 9 kda fragment of arabinogalactan.an arabinogalactan conjugate containing a 9 kda fragment of arabinogalactan and adenine-9-beta-d-arabinofuranoside 5'-monophosphate (araamp), denoted ag(9 kda)-araamp, has been synthesized and characterized. in 2.2.15 (human hepatoblastoma) cells, the attachment of araamp to ag(9 kda), a ligand of the asialoglycoprotein receptor, decreased the effective concentration for inhibiting extracellular hepatitis b virus (hbv) production by 90% (ec90) from 17 to 0.9 microm adenine arabinoside (araa) equ ...199611322248
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
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
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
loss and acquisition of duck hepatitis b virus integrations in lineages of lmh-d2 chicken hepatoma cells.hepatocellular carcinoma is the culmination of a series of genetic events which progressively alter the phenotype of a hepatocyte toward malignancy. hepadnaviral dna integrations are agents of genetic change which can promote the process of hepatocarcinogenesis. we previously characterized episomally derived duck hepatitis b virus (dhbv) integrations in lmh-d2 cells that replicate wild-type dhbv. in an effort to understand how integrations function as agents of progressive genetic change, we hav ...19968627726
chimeric hepatitis b virus core particles as probes for studying peptide-integrin interactions.an rgd-containing epitope from the foot-and-mouth disease virus (fmdv) vp1 protein was inserted into the e1 loop of the hepatitis b virus core (hbc) protein. this chimeric protein was expressed at high levels in escherichia coli and spontaneously assembled into virus-like particles which could be readily purified. these fusion particles elicited high levels of both enzyme-linked immunosorbent assay- and fmdv-neutralizing antibodies in guinea pigs. the chimeric particles bound specifically to cul ...19968648742
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
natural populations of woodchuck hepatitis virus contain variant precore and core sequences including a premature stop codon in the epsilon motif.we have determined a consensus sequence and the type and the frequency of spontaneous sequence variations in the woodchuck hepatitis virus (whv) precore gene and the 5' region of the core gene in 101 serum samples from 53 naturally whv-infected woodchucks by polymerase chain reaction sequencing. twenty of the 53 woodchucks were found to have variant sequences. ten patterns of variant sequences were identified in these 20 animals. whv sequences from 4 woodchucks had 1 nucleotide change, 3 had 2 n ...19968659124
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
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 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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
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