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retrospective analysis of an outbreak of b virus infection in a colony of debrazza's monkeys (cercopithecus neglectus).in 1981, an outbreak of herpetic disease developed in a colony of debrazza's monkeys (cercopithecus neglectus). in seven of eight infected animals, clinical signs of infection included vesicular and ulcerative lesions on the lips, tongue, and/or palate. histologic examination of lesions revealed intranuclear inclusion bodies, and electron microscopy revealed nucleocapsids and virions with typical herpesvirus morphology. although a virus was isolated that appeared similar to monkey b virus, techn ...200011200573
key determinants in the occurrence of clonal variation in humanized antibody expression of cho cells during dihydrofolate reductase mediated gene amplification.recombinant chinese hamster ovary (cho) parental clones expressing a humanized antibody against s surface antigen of hepatitis b virus were obtained by cotransfection of heavy chain (hc) and light chain (lc) cdna expression vectors into dihydrofolate reductase (dhfr)-deficient cho cells. when 23 representative parental clones were subjected to stepwise selection for increasing methotrexate (mtx) resistance, such as 0.02, 0.08, 0.32, and 1.0 microm, their clonal variations in regard to antibody e ...200111170482
immune responses following simian/human immunodeficiency virus (shiv) challenge of rhesus macaques after human immunodeficiency virus (hiv)-1 third variable domain (v3) loop-based genetic immunization.following dna immunization of rhesus macaques with a plasmid encoding the human immunodeficiency virus (hiv)-1 third variable domain (v3) loop, presented by pseudo-viral envelope particles of hepatitis b virus, specific immune responses were induced. the primates were then inoculated with a chimeric simian/human immunodeficiency virus (shiv). all the animals were infected, but the v3-specific immunization provided a relative attenuation of the acute phase of infection in the absence of neutraliz ...200011168828
antiviral efficacy of lobucavir (bms-180194), a cyclobutyl-guanosine nucleoside analogue, in the woodchuck (marmota monax) model of chronic hepatitis b virus (hbv) infection.lobucavir (bms-180194), a cyclobutyl-guanosine nucleoside analogue, effectively reduced whv-viremia in chronically infected carrier woodchucks (marmota monax) by daily per os treatment. whv-viremia in the animals was measured by the serum content of hybridizable whv-genomic dna. lobucavir, given at daily doses of 10 and 20 mg/kg body weight, reduced whv-viremia by a 10- to 200-fold range during therapy. lobucavir, given at 5 mg/kg, suppressed whv-viremia by a 10- to 30-fold range, whereas a 0.5 ...200011164506
limited proteolysis induces woodchuck hepatitis virus infectivity for human hepg2 cells.previous work from our laboratory has shown that digestion of hepatitis b virus (hbv) with v8 protease rendered the virus infectious for human hepatoblastoma cell line (hepg2). it was hypothesized that the cleavage exposes a 16 amino acid region that includes a consensus 'fusion' motif necessary to mediate infectivity. since woodchuck hepatitis virus (whv) and hbv possess significant homology in this region of their envelope proteins, including the v8 protease cleavage site, the possibility that ...200111163642
in vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus.woodchuck hepatitis virus (whv) and human hepatitis b virus are closely related, highly hepatotropic mammalian dna viruses that also replicate in the lymphatic system. the infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. in this study, hepato- and lymphotropism of whv produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid cell cultures and coculture systems, and virus pathogenicity wa ...200111160675
hepatitis b virus (hbv) virion and covalently closed circular dna formation in primary tupaia hepatocytes and human hepatoma cell lines upon hbv genome transduction with replication-defective adenovirus vectors.hepatitis b virus (hbv), the causative agent of b-type hepatitis in humans, is a hepatotropic dna-containing virus that replicates via reverse transcription. because of its narrow host range, there is as yet no practical small-animal system for hbv infection. the hosts of the few related animal viruses, including woodchuck hepatitis b virus and duck hepatitis b virus, are either difficult to keep or only distantly related to humans. some evidence suggests that tree shrews (tupaias) may be suscep ...200111152483
targeting murine immune responses to selected t cell- or antibody-defined determinants of the hepatitis b surface antigen by plasmid dna vaccines encoding chimeric antigen.by exchanging sequences from the middle-surface (ms) and small-surface (s) ag of hepatitis b virus (hbv) with corresponding sequences of the ms ag of woodchuck hepatitis virus, we constructed chimeric ms variants. using these constructs as dna vaccines in mice, we selectively primed highly specific (non-cross-reactive) ab responses to pre-s2 of the hbv ms ag and the "a" determinant of the hbv s ag, as well as l(d)- or k(b)-restricted ctl responses to hbv s epitopes. in transgenic mice that const ...200111145726
antiviral activity of clevudine [l-fmau, (1-(2-fluoro-5-methyl-beta, l-arabinofuranosyl) uracil)] against woodchuck hepatitis virus replication and gene expression in chronically infected woodchucks (marmota monax).l: -fmau [1-(2-fluoro-5-methyl-beta,l-arabinofuranosyl) uracil] has been shown to be an effective inhibitor of hepatitis b virus (hbv) and duck hepatitis b virus replication in cell culture and duck hepatitis b virus replication in acutely infected peking ducks. the woodchuck hepatitis virus (whv) and its natural host, the eastern woodchuck (marmota monax), have been established as a predictive model for the evaluation of antiviral therapies against chronic hbv infection. in this report, the ant ...200111124844
antiviral l-nucleosides specific for hepatitis b virus infection.a unique series of simple "unnatural" nucleosides has been discovered to inhibit hepatitis b virus (hbv) replication. through structure-activity analysis it was found that the 3'-oh group of the beta-l-2'-deoxyribose of the beta-l-2'-deoxynucleoside confers specific antihepadnavirus activity. the unsubstituted nucleosides beta-l-2'-deoxycytidine, beta-l-thymidine, and beta-l-2'-deoxyadenosine had the most potent, selective, and specific antiviral activity against hbv replication. human dna polym ...200111120971
combination therapy with lamivudine and adenovirus causes transient suppression of chronic woodchuck hepatitis virus infections.treatment of hepatitis b virus carriers with the nucleoside analog lamivudine suppresses virus replication. however, rather than completely eliminating the virus, long-term treatment often ends in the outgrowth of drug-resistant variants. using woodchucks chronically infected with woodchuck hepatitis virus (whv), we investigated the consequences of combining lamivudine treatment with immunotherapy mediated by an adenovirus superinfection. eight infected woodchucks were treated with lamivudine an ...200011090175
naturally occurring woodchuck hepatitis virus (whv) deletion mutants in chronically whv-infected woodchucks.deletion mutants of hepatitis b virus (hbv) are often found in chronically hbv-infected patients. it has not been possible to study the significance of such deletion mutants on liver diseases in a suitable animal model. in this study, we characterized naturally occurring deletion mutants of woodchuck hepatitis virus (whv) in 11 chronically whv-infected woodchucks. deletions within the whv pres region (nt 2992-338) had a length of 72 or 84 bp and were located in the amino terminal part of pres1. ...200011080471
puumala (puu) hantavirus strain differences and insertion positions in the hepatitis b virus core antigen influence b-cell immunogenicity and protective potential of core-derived particles.hepatitis b virus (hbv) core-derived chimeric particles carrying a puumala (puu) hantavirus (strain vranica/hällnäs) nucleocapsid (n) protein sequence (aa 1-45), alternatively inserted at three distinct positions (n-, c-terminus, or the internal region), and mosaic particles consisting of hbv core as well as core/puu (vranica/hällnäs) n (aa 1-45) readthrough protein were generated. chimeric particles carrying the insert at the n-terminus or the internal region of core induced some protective imm ...200011040127
nucleosomes are major t and b cell autoantigens in systemic lupus erythematosus.double-stranded dna (dsdna) is a well-known target of autoantibodies in systemic lupus erythematosus (sle). the majority of these autoantibodies are of the igg isotype and show affinity maturation, both of which are known hallmarks of t cell help. t cell responses to autoantigens, including dna, have been reported only incidentally in sle patients. nevertheless, in murine sle, naked dna and complexed dna (nucleosomes) are known to be recognized by t cells. this study aimed to characterize the an ...200011037891
identification of five different patr class i molecules that bind hla supertype peptides and definition of their peptide binding motifs.we have sequenced the pan troglodytes class i (patr) molecules from three common chimpanzees and expressed them as single molecules in a class i-deficient cell line. these lines were utilized to obtain purified class i molecules to define the peptide binding motifs associated with five different patr molecules. based on these experiments, as well as analysis of the predicted structure of the b and f polymorphic mhc pockets, we classified five patr molecules (patr-a*0101, patr-b*0901, patr-b*0701 ...200011035079
temporal pathogenesis of experimental neonatal woodchuck hepatitis virus infection: increased initial viral load and decreased severity of acute hepatitis during the development of chronic viral infection.acute hepatitis b virus (hbv) infections either resolve or progress to chronicity. identification of early deviations in host-virus responses associated with these outcomes can further differentiate cause-effect mechanisms that initiate and maintain chronicity. neonatal woodchucks were infected experimentally with the woodchuck hepatitis virus (whv) at 3 days of age. at 8 or 14 weeks of age (i.e. , the early- or mid-acute stage of infection), whole blood and large surgical biopsies of the liver ...200011003627
48-mer synthetic peptide analogue of the hepatitis b virus "a" determinant induces an anti-hbs antibody response after a single injection.an extended (48 amino acid) synthetic peptide analogue of the hepatitus b virus (hbv) s protein (hbsag) 'a' determinant has been produced by using 9-fluorenylmethoxycarbonyl (fmoc) chemistry and a low substitution polystyrene resin as the solid phase support. this peptide (s121/48) elicited a sustained anti-peptide antibody response in balb/c (h-2(d)) mice when immunised with freund's complete adjuvant (fca). cross-reactive, anti-hbs antibodies were induced, directed against a significant propor ...200011002244
high-level synthesis of human prolactin in chinese-hamster ovary cells.two eukaryotic human prolactin (hprl) expression vectors, based on a selectable dihydrofolate reductase (dhfr) marker, were used to transfect dhfr(-) chinese- hamster ovary (cho) cells. one vector, p658-hprl, contains the hepatitis-b virus-x cdna coding for a viral transactivator and sequences mediating dhfr mrna degradation. the other, peddc-hprl, carries the encephalomyocarditis virus leader sequence coupled to hprl cdna to provide high-level protein expression, possibly via a mechanism of int ...200011001873
limitations to replication of hepatitis delta virus in avian cells.human hepatitis delta virus (hdv) is a natural subviral agent that uses hepatitis b virus as a helper. experimentally, hdv can be made to replicate in woodchucks, using woodchuck hepatitis b virus as a helper virus. also, independent of such helper activity, replication of the hdv rna genome can be achieved in many mammalian cells. in this study we examined whether such replication could also be achieved in avian cells. we used cotransfection strategies and initially found no detectable genome r ...200010982328
correct binding of viral x protein to uvddb-p127 cellular protein is critical for efficient infection by hepatitis b viruses.a fully effective treatment of chronic human hepatitis b virus (hbv) infection is still missing and hbv remains the first etiological agent of liver cancer. although the viral regulatory x protein is essential for infection, its mode of action remains obscure, due the lack of an in vitro infection system. in the accompanying study, we showed the functional importance of interaction between x and the host protein uvddb-p127, in the transactivation and apoptotic properties of the viral protein. he ...200010980618
enhanced antiviral benefit of combination therapy with lamivudine and alpha interferon against whv replication in chronic carrier woodchucks.cell culture studies in our laboratory previously demonstrated synergistic antiviral activity for the combinations of lamivudine and a novel recombinant hybrid human alpha b/d interferon (rhu alpha b/d ifn) against hepatitis b virus (hbv) replication. based on these results, a study was designed to determine if an enhanced antiviral effect with this drug combination could be demonstrated in vivo using the woodchuck hepatitis virus (whv)/woodchuck experimental model of chronic hbv infection. both ...200010971862
the collagen repeat sequence is a determinant of the degree of herpesvirus saimiri stp transforming activity.herpesvirus saimiri (hvs) is divided into three subgroups, a, b, and c, based on sequence divergence at the left end of genomic dna in which the saimiri transforming protein (stp) resides. subgroup a and c strains transform primary common marmoset lymphocytes to interleukin-2-independent growth, whereas subgroup b strains do not. to investigate the nononcogenic phenotype of the subgroup b viruses, stp genes from seven subgroup b virus isolates were cloned and sequenced. consistent with the lack ...200010933720
herpes b-virus specific-pathogen-free breeding colonies of macaques (macaca mulatta): diagnostic testing before and after elimination of the infection.the national institutes of health's (nih) national center for research resources' (ncrr) division of comparative medicine has funded the establishment of specific pathogen-free (spf) captive macaque colonies. herpes b-virus (herpesvirus simiae, cercopithecine herpesvirus type 1) has been targeted for elimination. late seroconversion presents the greatest threat to the integrity of spf colonies. the purpose of the study reported here was to evaluate that threat through detailed investigation of t ...200010894500
increased hepatocyte turnover and inhibition of woodchuck hepatitis b virus replication by adefovir in vitro do not lead to reduction of the closed circular dna.the aim of this study was to evaluate the inhibitory effect of the nucleotide analogue adefovir on woodchuck hepatitis b virus (whv) replication and, in particular, to determine whether the pool of covalently closed circular dna (cccdna) could be reduced by adefovir treatment in primary cultures of woodchuck hepatocytes isolated from a chronic carrier. strong reduction of whv-dna synthesis (90%) and secretion (up to 98%) was observed with all 3 doses of adefovir used (1, 10, and 100 micromol/l), ...200010869302
mutations in the p53 tumor suppressor gene in tree shrew hepatocellular carcinoma associated with hepatitis b virus infection and intake of aflatoxin b1.infection with hepadnaviruses and exposure to aflatoxin b1 (afb1) are considered to be major risk factors in the development of hepatocellular carcinoma (hcc) in humans. a high rate of p53 mutations at codon 249 has been reported in these tumors. the tree shrew (tupaia belangeri chinensis) is a useful animal model for the development of hcc after human hepatitis b virus (hbv) infection or afb1 treatment. therefore, it was of particular interest to determine whether the p53 gene in tree shrew hcc ...200010863098
antiviral activities of oral 1-o-hexadecylpropanediol-3-phosphoacyclovir and acyclovir in woodchucks with chronic woodchuck hepatitis virus infection.acyclovir triphosphate is a potent inhibitor of hepatitis b virus dna polymerase, but acyclovir treatment provides no benefit in patients with hepatitis b virus infection. this is due in part to the fact that hepatitis b virus, unlike herpes simplex virus, does not code for a viral thymidine kinase which catalyzes the initial phosphorylation of acyclovir. we synthesized 1-o-octadecyl-sn-glycero-3-phospho (3-p)-acyclovir and found that it was highly active in reducing hepatitis b virus replicatio ...200010858362
effect of oral administration of emtricitabine on woodchuck hepatitis virus replication in chronically infected woodchucks.emtricitabine [(-)ftc] [(-)-beta-2', 3'-dideoxy-5-fluoro-3'-thiacytidine] has been shown to be an effective inhibitor of hepatitis b virus (hbv) in cell culture, with a potency and selectivity that are essentially identical to those of lamivudine. the antiviral activity of oral administration of (-)ftc against whv replication in chronically infected woodchucks, an established and predictive model for antiviral therapy against hbv, was examined in a placebo-controlled study. (-)ftc significantly ...200010817750
influenza b virus in seals.influenza b virus is a human pathogen whose origin and possible reservoir in nature are not known. an influenza b virus was isolated from a naturally infected harbor seal (phoca vitulina) and was found to be infectious to seal kidney cells in vitro. sequence analyses and serology indicated that influenza virus b/seal/netherlands/1/99 is closely related to strains that circulated in humans 4 to 5 years earlier. retrospective analyses of sera collected from 971 seals showed a prevalence of antibod ...200010807575
occult persistence and lymphotropism of hepadnaviral infection: insights from the woodchuck viral hepatitis model.hepatitis b virus (hbv) is a major human pathogen that causes chronic infection and life-threatening liver diseases in millions of individuals. while pathological and epidemiological consequences of clinically evident hbv infections are well recognized, there is no similar knowledge on an asymptomatic, silently progressing virus persistence. contrary to previous opinion, current evidence indicates that a serologically undetectable (occult) hbv carriage is a common outcome of recovery from sympto ...200010807510
reduction of aflatoxin b(1) adduct biomarkers by oltipraz in the tree shrew (tupaia belangeri chinensis).the risk of liver cancer is greatest in people both infected with hepatitis b virus (hbv) and highly exposed to aflatoxin b(1) (afb(1)). the tree shrew (tupaia belangeri chinensis) is a unique species that can be infected with human hbv, is susceptible to afb(1)-induced liver cancer, and shows a synergistic interaction between hbv and afb(1) for liver cancer. in this regard, the tree shrew may be useful for evaluating experimental chemoprevention strategies relevant to high-risk human population ...200010799742
susceptibility of chacma baboons (papio ursinus orientalis) to infection by hepatitis b virus.because baboons are being considered as a source of xenografts for human liver transplantation in patients with hepatitis b virus- (hbv) induced cirrhosis to forestall infection of the graft by the virus, we undertook a study to ascertain if baboons are resistant to hbv infection.200010798766
treatment of chronic woodchuck hepatitis virus infection in the eastern woodchuck (marmota monax) with nucleoside analogues is predictive of therapy for chronic hepatitis b virus infection in humans.the woodchuck hepatitis virus (whv) and its natural host, the eastern woodchuck (marmota monax), have been established as a model of hepatitis b virus (hbv)-induced disease. several published studies have used this experimental animal model system to demonstrate potential antiviral therapies for chronic hbv infections. however, there has been little comparative information available on compounds used in clinical anti-hbv studies in whv-infected woodchucks, thereby making interpretations of the p ...200010796894
posttranscriptional inhibition of class i major histocompatibility complex presentation on hepatocytes and lymphoid cells in chronic woodchuck hepatitis virus infection.woodchuck hepatitis virus (whv), similar to human hepatitis b virus, causes acute liver inflammation that can progress to chronic hepatitis and hepatocellular carcinoma. whv also invades cells of the host lymphatic system, where it persists for life. we report here that acute and chronic hepadnavirus hepatitis is characterized by a profound difference in the expression of class i major histocompatibility complex (mhc) molecules on the surface of infected hepatocytes and, notably, lymphoid cells. ...200010775584
enhanced antiviral benefit of combination therapy with lamivudine and famciclovir against whv replication in chronic whv carrier woodchucks.cell culture studies in our laboratory and others have previously demonstrated synergistic antiviral activity for combinations of 3tc (lamivudine) and penciclovir against hepatitis b virus (hbv) replication and the duck hepatitis b virus (dhbv). based on these results, a study was designed to determine if an enhanced antiviral effect with combinations of 3tc and famciclovir (fcv, oral prodrug of penciclovir) could be demonstrated in vivo using the woodchuck hepatitis virus (whv)/woodchuck experi ...200010774587
detection of hepatitis b virus infection in wild-born chimpanzees (pan troglodytes verus): phylogenetic relationships with human and other primate genotypes.infection with hepatitis b virus (hbv) was detected by serological testing for hbv surface antigen and by pcr assay for hbv dna in serum samples from two common chimpanzees (pan troglodytes subsp. verus) born in west africa. the complete genome sequences obtained by nucleotide sequencing of overlapping dna fragments amplified by pcr were compared with hbv variants recovered from other primates and with human genotypes a to f. both chimpanzee sequences were 3, 182 nucleotides in length, and the s ...200010756039
preclinical investigation of l-fmau as an anti-hepatitis b virus agent.preclinical aspects of a potent anti-hepatitis b virus (hbv) l-nucleoside, 1-(2-fluoro-5-methyl-beta-l-arabino-furanosyl)uracil (l-fmau) are described. l-fmau was prepared from l-ribose derivatives via either l-xylose or l-arabinose. l-fmau shows potent antiviral activity against hepatitis b virus (ec50 5.0 microm in h1 cells) with high selectivity in vitro. l-fmau is not incorporated into mitochondrial dna and no significant lactic acid production was observed in vitro. l-fmau is phosphorylated ...199810726061
woodchuck lymphotoxin-alpha, -beta and tumor necrosis factor genes: structure, characterization and biological activity.we cloned and characterized the woodchuck tumor necrosis factor (tnf) and lymphotoxin-alpha, -beta (lt-alpha, -beta) cdnas, genes and proteins to facilitate study of the functions of these cytokines during the course of woodchuck hepatitis virus (whv) infection. woodchuck cdna and genomic dna libraries were screened with woodchuck-specific dna probes to isolate the cdna and gene clones for tnf, lt-alpha and lt-beta. the cdnas for woodchuck tnf, lt-alpha and lt-beta code for proteins of 233, 205 ...200010721723
immune responses to duck hepatitis b virus infection.the duck hepatitis b virus (dhbv) was the first hepatitis b virus identified from an avian host. it is a member of the hepadnaviridae family of viruses. all members of this family display similar genomic organization and replication strategies and cause species-specific infections that result in either transient (acute) or persistent infection. hepadnavirus infection occurs primarily in hepatocytes in the liver with release of infectious virions and non-infectious 'empty' surface antigen particl ...200010717294
kemri hep-cell ii hepatitis b surface antigen screening kit.kenya is a high hepatitis b virus (hbv) endemic zone. prevention of hbv transmission by transfusing safe blood is necessary. kits for screening hepatitis b surface antigen (hbsag) are usually imported and are expensive. hence it has been difficult to screen donated and patient blood samples all over kenya.199910685326
full-genome sequence analyses of hepatitis b virus (hbv) strains recovered from chimpanzees infected in the wild: implications for an origin of hbv.hepatitis b virus (hbv) belongs to the genus orthohepadnavirus of the family hepadnaviridae. having been found in various animals (duck, heron, woodchuck, ground squirrel, and primates), hepadnaviruses must have undergone a long history of evolution and may comprise more members than currently recognized. chimpanzees may also have their own hepadnavirus, even if it might be very close to hbv. we analyzed hbv-like sequences from three chimpanzees (pan troglodytes) that were most likely infected d ...200010648183
apoptosis and regeneration of hepatocytes during recovery from transient hepadnavirus infections.it is well known that hepatitis b virus infections can be transient or chronic, but the basis for this dichotomy is not known. to gain insight into the mechanism responsible for the clearance of hepadnavirus infections, we have performed a molecular and histologic analysis of liver tissues obtained from transiently infected woodchucks during the critical phase of the recovery period. we found as expected that clearance from transient infections occurred subsequent to the appearance of cd4(+) and ...200010627561
phyllanthus orbicularis aqueous extract: cytotoxic, genotoxic, and antimutagenic effects in the cho cell line.the present work evaluates the cytotoxic, genotoxic, and antimutagenic effects of phyllanthus orbicularis (plant of genus phyllantus) aqueous extract in chinese hamster ovary (cho) cells. p. orbicularis aqueous extracts are used in cuban traditional medicine for their antiviral activity against hepatitis b virus and a and b flu virus. the cytotoxicity of the extract was tested by means of colony-forming ability and growth-inhibition assays as well as by measuring the mitotic index. apoptosis ind ...199910620480
effects of age and viral determinants on chronicity as an outcome of experimental woodchuck hepatitis virus infection.acute hepadnavirus infections either resolve or progress to chronicity. factors that influence chronicity as an outcome of hepatitis b virus (hbv) infection in humans can be studied experimentally in the woodchuck model. accordingly, several woodchuck hepatitis virus (whv) inocula were characterized. representative inocula had high titers of infectious virus (approximately 10(7.7)-10(9.5) woodchuck 50% infectious doses per milliliter [wid(50%)/ml] by subcutaneous inoculation), with 1 wid(50%) ra ...200010613745
echoviruses and coxsackie b viruses that use human decay-accelerating factor (daf) as a receptor do not bind the rodent analogues of daf.many serotypes of echovirus (ev) and coxsackie b virus (cbv) bind human decay-accelerating factor (daf) and use it as a receptor for infection. analogues for daf have been isolated from mice and rats and characterized; these analogues have amino acid identities to human daf of approximately 60%. ev serotypes 3, 6', 7, 11-13, and 29 and cbv serotypes 1, 3, and 5 caused hemagglutination of human erythrocytes but not rat or mouse erythrocytes, suggesting failure to bind rodent daf. to confirm this ...200010608785
hepatitis b virus x protein: structure, function and biology.the x gene is conserved among mammalian hepadnaviruses and the x protein, px, is essential for viral propagation at least in the woodchuck. during the last decade, efforts have centered on elucidating the oncogenic role of px in hepatitis b virus infection. the accumulating knowledge on px indicates that it is a multifunctional regulatory protein which modulates many host functions by communicating directly or indirectly with a variety of host targets as is the case for many viral regulatory pro ...199910516464
unraveling hepatitis b virus infection of mice and men (and woodchucks and ducks) 199910502809
evaluation of immune responses to inactivated influenza vaccines prepared in embryonated chicken eggs and mdck cells in a mouse model.this study was initiated with the isolation of influenza a and b viruses from clinical throat swabs in both fertile chicken eggs (egg) and mdck cells, which were used in subsequent vaccine production in the above two hosts. on the basis of haemagglutination-inhibiting (hi) tests, immune mouse sera from mice vaccinated with mdck cell-derived vaccines revealed antigenic similarities among h3n2 or b viruses isolated in mdck cells or eggs. similarly, antiserum prepared by immunization with egg-deriv ...199910494959
a new avian hepadnavirus infecting snow geese (anser caerulescens) produces a significant fraction of virions containing single-stranded dna.we describe the identification and functional analysis of an evolutionary distinct new avian hepadnavirus. infection of snow geese (anser caerulescens) with a duck hepatitis b virus (dhbv)-related virus, designated sghbv, was demonstrated by detection of envelope proteins in sera with anti-dhbv pres and s antibodies. comparative sequence analysis of the pcr-amplified sghbv genomes revealed unique sghbv sequence features compared with other avian hepadnaviruses. unlike dhbv, sghbv shows an open r ...199910489339
identification and expression of glycine decarboxylase (p120) as a duck hepatitis b virus pre-s envelope-binding protein.a 120-kilodalton protein (p120) was identified in the duck liver that binds to several truncated versions of duck hepatitis b virus (dhbv) pre-s envelope protein, suggesting p120 may serve as a dhbv co-receptor. the amino acid sequences of tryptic peptides from purified p120 were found to be the duck p protein of the glycine decarboxylase complex (dgd). dgd cdna cloning revealed extensive protein conservation with the chicken homologue except for several insertions in the n-terminal leader seque ...199910488106
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
fusogenic activity of hepadnavirus peptides corresponding to sequences downstream of the putative cleavage site.sequence homology between the amino-terminal region of the s protein of hepatitis b virus (hbv) and known fusion peptides from retroviruses and paramyxoviruses led us to propose that this region might be equally involved in the initial infective steps of hepadnaviruses. in fact, we showed that a synthetic peptide corresponding to the n-terminus region of the s protein of hbv had membrane-interacting properties and was able to induce liposome fusion adopting an extended (beta-sheet) conformation ...199910441561
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
perspectives for the treatment of hepatitis b virus infections.primarily resulting as a spin-off of the search for effective anti-hsv or anti-hiv agents, several compounds have been identified as effective and promising candidate anti-hbv drugs, i.e. famciclovir (penciclovir), bms-200475, lamivudine (3tc), (-)ftc, l(-)fd4c, l-fmau, dapd (dxg), bis(pom)-pmea and bis(poc)-pmpa. they all inhibit hbv replication in hep g2 2.2.15 at concentrations that are well below the cytotoxicity threshold. all these nucleoside analogues require three phosphorylation steps t ...199910418752
persistence of infectious hepadnavirus in the offspring of woodchuck mothers recovered from viral hepatitis.mother-to-child transmission is an important route for hepatitis b virus (hbv) dissemination. it has been established that hbv traces persist for years after complete clinical recovery from hepatitis b. similarly, resolution of hepatitis caused by hbv-related woodchuck hepatitis virus (whv) is followed by occult lifelong carriage of pathogenic virus. in this study, we documented that whv persisting after termination of acute hepatitis is transmittable to newborns as an asymptomatic long-term inf ...199910411550
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
synergistic effect of hepatitis b virus and aflatoxin b1 in hepatocarcinogenesis in tree shrews.an animal experiment with tree shrews was performed to detect the synergistic effects of hepatitis b virus (hbv) infection and dietary aflatoxin b1 (afb1) in hepatocarcinogenesis. adult healthy tree shrews (tupaia belangeri chinensis) were divided into four groups: group a (hbv + afb1)--animals were infected with human hbv serum at first, then fed afb1 diluted with milk, 150 ug/kg.bw/day, 6 days/week for 105 weeks. group b (hbv)--animals were infected with human hbv as group a, but no afb1 treat ...199910374028
the expression of insulin-like growth factor ii, hepatitis b virus x antigen and p21 in experimental hepatocarcinogenesis in tree shrews.the purpose of this paper was to study the mechanism of synergistic effect in hepatocarcinogenesis induced by hepatitis b virus (hbv) infection and aflatoxin b1 (afb1) intake. immunohistochemical staining was used in formalin-fixed, paraffin-embedded sections of cancer and liver tissues. the incidence of hepatocellular carcinomas (hccs) was 52.9% in experimental tree shrews that received both hbv and afb1. it was significantly higher than that of animals exposed to hbv (11.1%, group b), or (afb1 ...199910374027
[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
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
activation of the n-myc2 oncogene by woodchuck hepatitis virus integration in the linked downstream b3n locus in woodchuck hepatocellular carcinoma.in the woodchuck hepatitis virus (whv)/woodchuck model for hepatitis b virus-induced hepatocellular carcinoma, frequent activation of n-myc oncogenes by whv integration has been firmly established. n-myc2, the most frequently affected gene, was reported to be activated by whv insertion either in the proximity of the gene or in a distant uncoding locus, win. we previously reported that a whv integration cloned from a liver tumor was located in a chromosomal locus already described by others as th ...199910329558
pharmacokinetics of beta-l-2',3'-dideoxy-5-fluorocytidine in rhesus monkeys.beta-l-2',3'-dideoxy-5-fluorocytidine (beta-l-fddc), a novel cytidine analog with an unnatural beta-l sugar configuration, has been demonstrated by our group and others to exhibit highly selective in vitro activity against human immunodeficiency virus types 1 and 2 and hepatitis b virus. this encouraging in vitro antiviral activity prompted us to assess its pharmacokinetics in rhesus monkeys. three monkeys were administered an intravenous dose of [3h] beta-l-fddc at 5 mg/kg of body weight. follo ...199910103200
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
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
recombinant duck interferon gamma inhibits duck hepatitis b virus replication in primary hepatocytes.interferon gamma (ifn-gamma), which has been cloned in several mammalian species and recently in birds, plays a critical role in modulating immune system function. ifn-gamma and tumor necrosis factor alpha (tnf-alpha) have been shown to be crucial in the pathogenesis of viral hepatitis and in the transient disappearance of hepatitis b virus (hbv) from the liver after adoptive transfer of hbv-specific cytotoxic t lymphocytes into hbv-transgenic mice. similar studies in the natural animal hosts of ...199910074168
occult lifelong persistence of infectious hepadnavirus and residual liver inflammation in woodchucks convalescent from acute viral hepatitis.traces of hepatitis b virus (hbv) genome can persist for years following recovery from hepatitis b. to determine overall duration, molecular characteristics, and pathological implications of this serologically undetectable form of hepadnaviral carriage, we have analyzed the expression of transcriptionally active virus genomes, their infectivity, and examined liver alterations during the natural lifespan of woodchucks convalescent from acute infection with hbv- related woodchuck hepatitis virus ( ...199910051500
double-stranded linear duck hepatitis b virus (dhbv) stably integrates at a higher frequency than wild-type dhbv in lmh chicken hepatoma cells.integration of hepadnavirus dnas into host chromosomes can have oncogenic consequences. analysis of host-viral dna junctions of dhbv identified the terminally duplicated r region of the viral genome as a hotspot for integration. since the r region is present on the 5' and 3' ends of double-stranded linear (dsl) hepadnavirus dnas, these molecules have been implicated as integration precursors. we have produced a lmh chicken hepatoma cell line (lmh 66-1 dsl) which replicates exclusively dsl duck h ...19999882355
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
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
[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
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
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
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
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
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
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
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
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
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
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
[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
[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
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
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
[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
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
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
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
the gdpal region of the pre-s1 envelope protein is important for morphogenesis of woodchuck hepatitis virus.the pre-s envelope protein of duck hepatitis b virus (dhbv) contains a region, asp-asp-pro-leu-leu (ddpll), that is specifically required for virus assembly and secretion (lenhoff and summers, j virol 1994;68:4565-4571). we found that amino acids 201 to 205 of the pre-s envelope protein of woodchuck hepatitis virus (whv) form a conserved amino acid cluster, gly-asp-pro-ala-leu (gdpal), which resembles the ddpll sequence of dhbv. to determine whether the gdpal region was functionally equivalent t ...19989581699
isolation of a hepadnavirus from the woolly monkey, a new world primate.hepatitis b virus (hbv) infections are a major worldwide health problem with chronic infections leading to cirrhosis and liver cancer. viruses related to human hbv have been isolated from birds and rodents, but despite efforts to find hepadnaviruses that infect species intermediate in evolution between rodents and humans, none have been described. we recently isolated a hepadnavirus from a woolly monkey (lagothrix lagotricha) that was suffering from fulminant hepatitis. phylogenetic analysis of ...19989576957
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
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
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
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
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
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
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
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
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
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
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
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