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a short sequence within domain c of duck carboxypeptidase d is critical for duck hepatitis b virus binding and determines host specificity.virus-cell surface receptor interactions are of major interest. hepadnaviruses are a family of partially double-stranded dna viruses with liver tropism and a narrow host range of susceptibility to infection. at least in the case of duck hepatitis b virus (dhbv), host specificity seems controlled partly at the receptor level. the middle portion in the pre-s region of the viral large envelope protein binds specifically to duck carboxypeptidase d (dcpd) but not to its human or chicken homologue. al ...200111602705
expansion of hbv-specific memory ctl primed by dual hiv/hbv genetic immunization during shiv primary infection in rhesus macaques.we have previously shown the induction of humoral and cytotoxic responses specific for human immunodeficiency virus (hiv) and hepatitis b virus (hbv) antigens, following genetic immunization of rhesus macaques with a plasmid encoding both the third variable domain of the hiv-1 external envelope glycoprotein and the pseudo-viral particle of hepatitis b surface antigen (hbsag) as presenting molecules. the dna-immunized primates and two control animals were then challenged with a chimeric simian/hu ...200111257382
replication of naturally occurring woodchuck hepatitis virus deletion mutants in primary hepatocyte cultures and after transmission to naive woodchucks.woodchuck hepatitis virus (whv) mutants with core internal deletions (cid) occur naturally in chronically whv-infected woodchucks, as do hepatitis b virus mutants in humans. we studied the replication of whv deletion mutants in primary woodchuck hepatocyte cultures and in vivo after transmission to naive woodchucks. by screening 14 wild-caught, chronically whv-infected woodchucks, two woodchucks, wh69 and wh70, were found to harbor whv cid mutants. consistent with previous results, whv cid mutan ...200111264370
novel hepatitis b virus strain from a chimpanzee of central africa (pan troglodytes troglodytes) with an unusual antigenicity of the core protein.we and others have previously reported a hepatitis b virus (hbv)-like hepadnavirus strain which seemed to be indigenous to west african chimpanzees (pan troglodytes verus). after that, we obtained an hbsag-positive serum sample from a chimpanzee from central africa, named bassi, belonging to another subspecies (p. troglodytes troglodytes). the full-genome nucleotide sequence of the hepadnavirus from bassi showed a significant difference (9-26%) from those so far reported from primates including ...200111684895
efficient infection of primary tupaia hepatocytes with purified human and woolly monkey hepatitis b virus.the asian tree shrew, tupaia belangeri, has been proposed as a novel animal model for studying hepatitis b virus (hbv) infection. here, we describe a protocol for efficient and reproducible infection of primary tupaia hepatocytes with hbv. we report that human serum interferes with hbv binding to the hepatocytes, thus limiting the maximum multiplicity of infection. purification of hbv virions by gradient sedimentation greatly enhances virus binding and infectivity. covalently closed circular dna ...200111333889
the woodchuck model of hepatitis b virus infection.the woodchuck hepatitis virus (whv) was the first of the mammalian and avian hepadnaviruses described after discovery of the virus of hepatitis b (hbv). woodchucks chronically infected with whv develop progressively severe hepatitis and hepatocellular carcinoma, which present as lesions that are remarkably similar to those associated with hbv infection in humans. the initial virological studies and studies of pathogenesis utilized woodchucks that had been trapped in the wild and had acquired whv ...200111406711
woodchuck hepatocytes remain permissive for hepadnavirus infection and mouse liver repopulation after cryopreservation.isolated hepatocytes represent a relevant model of the liver and are highly required both for research and therapeutic applications. however, sources of primary liver cells from human beings and from some animal species are limited. therefore, cryopreservation of hepatocytes could greatly facilitate advances in various research areas. the aim of this study was to evaluate whether cryopreserved primary woodchuck hepatocytes could be used for woodchuck hepatitis b virus (whv) infection studies, an ...200111584382
antigenic and genetic analyses of influenza b viruses isolated in lusaka, zambia in 1999.previous studies of the hemagglutinin (ha) genes of various influenza b virus isolates demonstrated the existence of two antigenically distinct virus lineages represented by b/victoria/2/87 and b/yamagata/16/88, respectively. here, we investigated the antigenic and genetic characteristics of influenza b viruses isolated from children living in lusaka, zambia between january and may 1999. antigenic analysis with chicken antiviral sera showed that all the zambian isolates had the ha protein belong ...200111699954
hbv integrants of hepatocellular carcinoma cell lines contain an active enhancer.hepatitis b virus (hbv) infection is a major risk factor worldwide for the development of hepatocellular carcinoma (hcc). integrated hbv dna fragments, often highly rearranged, are frequently detected in hcc. in woodchuck, the viral enhancer plays a central role in hepatocarcinogenesis, but in humans the mechanism of hbv oncogenesis has not been established. in this study we investigated the status of the viral enhancer in two human hcc cell lines, hep3b and plc/prf/5 each containing one or more ...200111687960
evaluation of novel strategies to combat hepatitis b virus targetting wild-type and drug-resistant mutants in experimental models.recent studies have shown that the kinetics of hepatitis b virus (hbv) clearance during antiviral therapy are slow, requiring long-term therapy to control viral replication. it has also been shown that emergence of resistant mutants is accelerated by high hbv replication and hepatocyte turnover, which are common features in patients with chronic hbv infection. it is therefore important to continue research on novel antiviral agents to design optimal combination strategies. the duck and woodchuck ...200111594680
x-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo.the x protein (hbx) of the hepatitis b virus (hbv) has been shown to be important for the establishment of hbv infection in vivo. our previous studies suggested that interaction of hbx with the proteasome complex may underlie the pleiotropic functions of hbx. in this study, we generated a series of woodchuck hepatitis virus (whv) x mutants, including mutants of the domain interacting with the proteasome, and studied their infectivity in woodchucks. many of the mutants were defective in transacti ...200111714744
t-helper cell response to woodchuck hepatitis virus antigens after therapeutic vaccination of chronically-infected animals treated with lamivudine.immunotherapy of patients chronically-infected with hepatitis b virus (hbv) may have the risk of fulminant hepatitis. this risk might be diminished if immunotherapy was carried out under conditions of low viremia.200111495027
management of hepatitis b virus infections in two gibbons and a western lowland gorilla in a zoological collection.since 1996, three primates newly arrived at london zoo have been found to be infected with hepatitis b virus. the species involved were white-cheeked gibbons (hylobates leucogenys leucogenys and hylobates leucogenys siki) and a western lowland gorilla (gorilla gorilla gorilla). the protocols for the practical management of these cases, including the immunisation of susceptible non-human primates and the staff with recombinant hepatitis b vaccine are described, and the origin and evolution of hep ...200111504202
detection of b virus infection in cynomolgus monkeys by elisa using simian agent 8 as alternative antigen.the use of simian agent 8 (sa8) as an antigen for b virus (bv) antibody detection was evaluated in cynomolgus monkeys. seventy-two sera judged as positive using bv antigen were all positive when the sa8 antigen was used. out of 28 bv-negative sera 2 were positive against the sa8 antigen and one serum was classified as indeterminate. the present data indicates that detection of bv antibody can be achieved accurately and safely by enzyme-linked immunosorbent assay (elisa) using sa8 antigen.200111515100
antibody responses of healthy infants to concurrent administration of a bivalent haemophilus influenzae type b-hepatitis b vaccine with diphtheria-tetanus-pertussis, polio and measles-mumps-rubella vaccines.to confirm that children given a bivalent haemophilus influenzae type b-hepatitis b vaccine (bivalent hib-hb vaccine; comvax) concurrently with priming doses of diphtheria-tetanus-pertussis vaccine (dtp), a booster dose of diphtheria-tetanus-acellular pertussis vaccine (dtap), inactivated or oral polio vaccine (ipv or opv) and measles-mumps-rubella vaccine (m-m-r(ii)) have satisfactory antibody responses to all antigens.200111520252
antiviral activity and intracellular metabolism of bis(tbutylsate) phosphotriester of beta-l-2',3'dideoxyadenosine, a potent inhibitor of hiv and hbv replication.the beta-l-nucleoside analogue beta-l-2',3'-dideoxy adenosine (beta-l-dda) has been shown to exhibit limited antiviral activities. this was attributed to its rapid catabolism through cleavage of the glycosidic bond and poor phosphorylation to the nucleotide beta-l-2',3'-dideoxyadenosine-5'-mono phosphate (beta-l-ddamp) (placidi et al., 2000). however, the nucleotide beta-l-2',3'-dideoxyadenosine-5'-triphosphate (beta-l-ddatp) inhibited the activity of both hiv-1 reverse transcriptase (rt) and vi ...200111527047
protection against woodchuck hepatitis virus (whv) infection by gene gun coimmunization with whv core and interleukin-12.woodchuck hepatitis virus (whv) and hepatitis b virus (hbv) are closely similar with respect to genomic organization, host antiviral responses, and pathobiology of the infection. t-cell immunity against viral nucleocapsid (hbcag or whcag) has been shown to play a critical role in viral clearance and protection against infection. here we show that vaccination of healthy woodchucks by gene gun bombardment with a plasmid coding for whcag (pcw) stimulates proliferation of whcag-specific t cells but ...200111533170
immunogenicity of a dna vaccine against herpes b virus in mice and rhesus macaques.herpes b virus (cercopithecine herpesvirus 1) is endemic in captive macaque populations and poses a serious threat to humans who work with macaques or their tissues. a vaccine that could prevent or limit b virus infection in macaques would lessen occupational risk. to that end, a dna vaccine plasmid expressing the b virus glycoprotein b (gb) was constructed and tested for immunogenicity in mice and macaques. intramuscular (im) or intradermal (id) immunization in mice elicited antibodies to gb th ...200111535340
paired chimpanzee hepatitis b virus (chhbv) and mtdna sequences suggest different chhbv genetic variants are found in geographically distinct chimpanzee subspecies.the surface antigen gene region from five chronic hepatitis b virus (hbv) infected chimpanzees was amplified by pcr and the sequence determined. sequence comparison confirmed that all of the sequences were chimpanzee hepatitis b virus (chhbv) and they appeared to represent three distinct clusters or branches. to address the question of whether the three branches represented recently identified subspecies of chimpanzees, we determined the sequence of the mitochondrial dna hypervariable d loop fro ...200111551650
anti-hbv specific beta-l-2'-deoxynucleosides.a unique series of simple unnatural l-nucleosides that specifically inhibit hepatitis b virus (hbv) replication has been discovered. these molecules have in common a hydroxyl group in the 3'-position (3'-oh) of the beta-l-2'-deoxyribose sugar that confers antiviral activity specifically against hepadnaviruses. replacement of the 3'-oh broadens activity to other viruses. substitution in the base decreases antiviral potency and selectivity. human dna polymerases and mitochondrial function are not ...200111563077
ddb2 induces nuclear accumulation of the hepatitis b virus x protein independently of binding to ddb1.the hepatitis b virus (hbv) x protein (hbx) is critical for the life cycle of the virus. hbx associates with several host cell proteins including the ddb1 subunit of the damaged-dna binding protein ddb. recent studies on the x protein encoded by the woodchuck hepadnavirus have provided correlative evidence indicating that the interaction with ddb1 is important for establishment of infection by the virus. in addition, the interaction with ddb1 has been implicated in the nuclear localization of hb ...200111581406
identification and analysis of a new hepadnavirus in white storks.we identified, cloned, and functionally characterized a new avian hepadnavirus infecting storks (sthbv). sthbv has the largest dna genome of all avian hepadnaviruses and, based on sequence and phylogenetic analysis, is most closely related to, but distinct from, heron hepatitis b virus (hhbv). unique for sthbv among the other avian hepadnaviruses is a potential hnf1 binding site in the pres promoter. in common only with hhbv, sthbv has a myristylation signal on the s and not the pres protein, tw ...200111601923
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
testing of corneoscleral discs and their culture media of seropositive donors for hepatitis b and c virus genomes.the prevalence of donors seropositive for hepatitis b virus (hbv) surface antigen (hbsag) or hepatitis c virus (hcv) antibody (anti-hcv) in western countries is estimated to be 0.5%-1%. there have been only two cases, however, published so far, where hepatitis b was suspected to have been transmitted by penetrating keratoplasty [4]. concerning hcv, no suspected transmission by keratoplasty has been reported so far. this is also true for the time before serological screening for infectious diseas ...200111760041
cloning and expression of a novel hepatitis b virus-binding protein from hepg2 cells.a direct involvement of the hepatitis b virus (hbv) pres1-(21-47) sequence in virus attachment to cell membrane receptor(s) and the presence on the plasma membranes of hepg2 cells of protein(s) with receptor activity for hbv have been suggested by many previous experiments. in this study, by using a tetravalent derivative of the pres1-(21-47) sequence, we have isolated by affinity chromatography from detergent-solubilized hepg2 plasma membranes a 44-kda protein (hbv-binding protein; hbv-bp), whi ...200111389143
inhibition of hepatitis b virus dna replication by imino sugars without the inhibition of the dna polymerase: therapeutic implications.previously we have shown that the imino sugar inhibitor of n-linked glycan processing, n-nonyl-deoxynojirimycin (n-nonyl-dnj), had antiviral activity in the woodchuck model of chronic hepatitis b virus (hbv) infection. in studying the mechanism of action of this compound, it was discovered that imino sugars could inhibit hbv secretion without inhibiting n-linked glycoprocessing. although n-nonyl-dnj is an inhibitor of the endoplasmic reticulum (er) glucosidase, here it is shown that n-nonyl-dnj ...200111391538
animal models of hepatitis delta virus infection and disease.hepatitis delta virus (hdv) is a defective rna virus with similarities to unusual subviral pathogens of higher plants. it requires hepatitis b virus (hbv) for its replication/transmission, and hbv-infected humans are the only established host. hdv causes both severe acute hepatitis and rapidly progressive chronic disease in some individuals. the hdv life cycle involves remarkable features, such as ribozyme- mediated autocatalytic processes, pol ii-directed rna synthesis from a single-stranded ci ...200111406712
experimental influenza b viral myositis.to investigate the pathogenesis of influenza myositis in animals, juvenile balb/c mice were inoculated with influenza b/lee virus intramuscularly into the right quadriceps muscle. chicken normal allantoic fluid (naf) or phosphate-buffered saline (pbs) was injected into the left quadriceps of control mice and in some virus-infected mice. serum creatinine phosphokinase (cpk) levels rose significantly on days 1 and 2 post-inoculation (pi) in only virus-inoculated mice. on days 2 and 3 pi, right qua ...200111440746
antiviral beta-l-nucleosides specific for hepatitis b virus infection.three simple, related nucleosides, beta-l-2'-deoxycytidine (ldc), beta-lthymidine (ldt), and beta-l-2'-deoxyadenosine (lda), have been discovered to be potent, specific and selective inhibitors of the replication hepatitis b virus (hbv), as well as the closely related duck and woodchuck hepatitis viruses (whv). structure-activity relationship analysis indicates that the 3'-oh group of the beta-l-2'-deoxyribose of the beta-l-2'-deoxynucleoside confers specific anti-hepadnavirus activity. the simp ...200111594678
interpretation of serological test results for simian herpes b virus.in 1992 an annual simian herpes b virus (bv) screening programme for an experimental group of macaque monkeys (macaca mulatta and macaca fascicularis) was initiated with the aim of establishing a specific pathogen free (spf) colony. in june 1999 one animal was found to be unexpectedly bv positive (non-negative). the investigation of this result highlights some of the issues and difficulties that may be encountered in such a programme.200111669314
differentially expressed genes in hepatocellular carcinoma induced by woodchuck hepatitis b virus in mice. 200111819834
enhanced transgene expression in primitive hematopoietic progenitor cells and embryonic stem cells efficiently transduced by optimized retroviral hybrid vectors.oncoretroviral vectors have been successfully used in gene therapy trials, yet low transduction rates and loss of transgene expression are still major obstacles for their application. to overcome these problems we modified the widely used moloney murine leukemia virus-derived retroviral vector pmx by replacing the 3'ltr with the spleen focus-forming virus ltr and inserting the woodchuck hepatitis b virus post-translational regulatory element. to compare requirements crucial for efficient transge ...200211948372
detection of duck hepatitis b virus dna on filter paper by pcr and sybr green dye-based quantitative pcr.duck hepatitis b virus (dhbv) belongs to the hepadnaviridae family, which includes human hepatitis b virus (hbv) and woodchuck hepatitis virus. it is widely distributed in wild and domestic ducks due to congenital transmission. hbv is a worldwide health problem, with carriers at risk of developing cirrhosis and liver cancer. medical staff and scientists working with hbv must be vaccinated because of its contagious nature. dhbv is a safe surrogate for hbv because of their similarities. collection ...200212089280
alphaherpesvirus antigen quantitation to optimize the diagnosis of herpes b virus infection.standardized, quantified virus antigen stocks are essential for dependable quality control of diagnostic assays. five simple, rapid and economical direct enzyme linked immunoassays (delisa) were developed to standardize and optimize antigen from five major cross-reacting alphaherpesviruses: herpes b virus, herpesvirus papio 2, langur monkey herpesvirus, herpes simplex virus-1 and herpes simplex virus-2. each delisa relied on pools of convalescent sera from rhesus monkeys, baboons, langurs and hu ...200211906729
parameters of human hepatitis delta virus genome replication: the quantity, quality, and intracellular distribution of viral proteins and rna.assembly of hepatitis delta virus (hdv) in infected human hepatocytes involves association of the 1,679- nucleotide single-stranded genomic rna (deltarna) with multiple copies of both small and large forms of the delta protein (deltaag) to form a ribonucleoprotein particle which in turn interacts with envelope proteins of the natural helper virus, hepatitis b virus. subsequently, for initiation of a new round of replication, the amount of small deltaag within the assembled hdv particle is both n ...200211907210
immunization with surface antigen vaccine alone and after treatment with 1-(2-fluoro-5-methyl-beta-l-arabinofuranosyl)-uracil (l-fmau) breaks humoral and cell-mediated immune tolerance in chronic woodchuck hepatitis virus infection.woodchucks chronically infected with the woodchuck hepatitis virus (whv) were treated with the antiviral drug 1-(2-fluoro-5-methyl-beta-l-arabinofuranosyl)-uracil (l-fmau) or placebo for 32 weeks. half the woodchucks in each group then received four injections of surface antigen vaccine during the next 16 weeks. vaccination alone elicited a low-level antibody response to surface antigen in most carriers but did not affect serum whv dna and surface antigen. carriers treated first with l-fmau to r ...200211991959
characterization of complex b cell epitopes on woodchuck hepatitis virus surface antigens by using plasmids encoding chimeric proteins and dna immunization.the conformational nature of the b cell epitopes on the hepadnavirus surface antigens makes its characterization difficult. here, a new approach by dna vaccination with plasmids expressing chimeric hepadnavirus surface antigens was explored to determine b cell epitopes on the surface antigens of woodchuck hepatitis virus (whsag). a series of chimeric genes consisting of complementary fragments of whsag and hepatitis b virus surface antigens (hbsag) was constructed. these plasmids expressed the f ...200212009876
pharmacology of beta-l-thymidine and beta-l-2'-deoxycytidine in hepg2 cells and primary human hepatocytes: relevance to chemotherapeutic efficacy against hepatitis b virus.beta-l-thymidine (l-dt) and beta-l-2'-deoxycytidine (l-dc) are potent and highly specific inhibitors of hepatitis b virus (hbv) replication both in vivo and in vitro (50% effective concentrations, 0.19 to 0.24 microm in 2.2.15 cells). the intracellular metabolisms of l-dt and l-dc were investigated in hepg2 cells and primary cultured human hepatocytes. l-dt and l-dc were extensively phosphorylated in both cell types, with the 5'-triphosphate derivative being the predominant metabolite. in hepg2 ...200212019082
antibody cross-reactivity of alphaherpesviruses as mirrored in naturally infected primates.the extent of antibody cross-reactivity of pooled antisera from rhesus monkeys, baboons, african green monkeys, langurs, sooty mangabeys and humans to 6 alphaherpesviruses (herpes b virus, herpes papio 2, simian agent 8, langur herpes virus and herpes simplex 1 & 2) was examined by two types of enzyme linked immunosorbent assays, an antibody capture assay (telisa) and an antigen capture assay (delisa). percent cross-reactivity was calculated for each serum by comparison of the homologous reactio ...200212021865
genetic variability in hepatitis b viruses.in 1988, it was reported that the full nucleotide sequences of 18 hepatitis b virus (hbv) strains clustered into four genetic groups (a to d) with more than 8% divergence between the groups. this classification of strains in terms of genome sequence has since proven to be an important tool in the understanding of hbv epidemiology and evolution and has been expanded to include three more genotypes. in parallel with the hbv genotypes described in humans, hbv strains isolated from different primate ...200212029141
experimental transfection of macaca sylvanus with cloned human hepatitis b virus.due to the absence of easily accessible animal models for the study of hepatitis b virus (hbv), the possibility of using macaca sylvanus, a monkey originating from morocco, north africa, was investigated. three monkeys were intrahepatically inoculated with a replication-competent head-to-tail hbv dna plasmid dimer construct. the hbv surface antigen and hbv dna were detected prior to alanine aminotransferase elevation in the serum of two of three hbv-inoculated monkeys at day 2 post-transfection ...200212075082
influenza activity in china: 1998-1999.during 1989-1999, influenza a h3n2 and h1n1 subtypes and b type viruses were still co-circulating in human population in china, while influenza a (h3n2) virus was predominant strain. the two antigenically and genetically distinguishable strains of influenza b virus were also still co-circulating in men in southern china. the antigenic analysis indicated that most of the h3n2 viruses were a/panama/2007/99 (h3n2)-like strain, the most of the h1n1 viruses were antigenically similar to a/beijing/262 ...200212110253
rescue of influenza b virus from eight plasmids.influenza b virus causes a significant amount of morbidity and mortality, yet the systems to produce high yield inactivated vaccines for these viruses have lagged behind the development of those for influenza a virus. we have established a plasmid-only reverse genetics system for the generation of recombinant influenza b virus that facilitates the generation of vaccine viruses without the need for time consuming coinfection and selection procedures currently required to produce reassortants. we ...200212172012
deficiencies in the acute-phase cell-mediated immune response to viral antigens are associated with development of chronic woodchuck hepatitis virus infection following neonatal inoculation.in vitro proliferation of peripheral blood mononuclear cells was used to measure virus-specific cell-mediated immunity (vcmi) following neonatal woodchuck hepatitis virus (whv) infection. fifteen neonates were inoculated with the w8 strain of whv. in 11, infection was resolved, and 4 became chronic carriers. nineteen neonates were inoculated with the w7 strain and all became chronic carriers. seven age-matched uninfected woodchucks served as controls. virologic and vcmi profiles among the w8 and ...200211799172
one-step pcr to distinguish b virus from related primate alphaherpesviruses.by adding betaine to the pcr mixture, we previously established a pcr method to amplify a dna segment of the glycoprotein g gene of b virus (bv) derived from a rhesus macaque. we have found that dna of other bv strains derived from cynomolgus, pigtail, and lion-tailed macaques can also serve as the template in our pcr assay. under the same conditions no product was obtained with dna of simian agent 8 of green monkeys and herpesvirus papio 2 of baboons, or the human herpes simplex viruses types 1 ...200211986284
viral dynamics during and after entecavir therapy in patients with chronic hepatitis b.nucleoside analogues inhibit hepatitis b virus (hbv) replication. entecavir, a new guanine nucleoside, has also been shown to reduce covalently closed circular dna (cccdna) to undetectable levels in woodchucks chronically infected with hepatitis virus. mathematical description of changes in viral load during and after therapy may help to understand the several events that take place during nucleoside analogue treatment.200212076873
human exposure to herpesvirus b-seropositive macaques, bali, indonesia.herpesvirus b (cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. however, the threat of herpesvirus b in nonlaboratory settings worldwide remains to be addressed. we investigated the potential for exposure to herpesvirus b in workers at a "monkey forest" (a temple that has become a tourist attraction because of its monkeys) in bali, indonesia. in july 2000, 105 ...200212141963
conserved transactivating and pro-apoptotic functions of hepadnaviral x protein in ortho- and avihepadnaviruses.two established activities of the multifunctional human hepatitis b virus x-protein are its transactivating and pro-apoptotic potential. we analysed whether x-proteins from other orthohepadnaviruses and the newly discovered avihepadnaviral x-proteins have similar functions as hbx. previously, we have shown that hbx suppresses oncogenic transformation of primary rat embryo fibroblasts (ref) by induction of apoptosis. using this system, we found that the wildtype x-proteins of woodchuck, ground sq ...200212242658
a modified hepatitis b virus core particle containing multiple epitopes of the plasmodium falciparum circumsporozoite protein provides a highly immunogenic malaria vaccine in preclinical analyses in rodent and primate hosts.despite extensive public health efforts, there are presently 200 to 400 million malaria infections and 1 to 2 million deaths each year due to the plasmodium parasite. a prime target for malaria vaccine development is the circumsporozoite (cs) protein, which is expressed on the extracellular sporozoite and the intracellular hepatic stages of the parasite. previous studies in rodent malaria models have shown that cs repeat b-cell epitopes expressed in a recombinant hepatitis b virus core (hbc) pro ...200212438363
development of viral disinfectant assays for duck hepatitis b virus using cell culture/pcr.human hepatitis b virus (hbv) is a worldwide public health problem with chronic carriers at risk for developing cirrhosis and hepatocellular carcinoma. accidental nosocomial infections from inadequately disinfected equipment or exposure to blood and body fluids from patients are major routes. to solve such problems, disinfectants to inactivate hbv must be validated. duck hepatitis b virus (dhbv) is accepted as a surrogate for hbv, due to their similar sensitivities to disinfectants and its safet ...200212367728
identification of a hepatitis b virus genome in wild chimpanzees (pan troglodytes schweinfurthi) from east africa indicates a wide geographical dispersion among equatorial african primates.dnas from four wild chimpanzees (pan troglodytes schweinfurthi) from eastern africa were screened for 14 dna viruses and retroviruses. between two and three viruses were found in each animal. an entire hepatitis b virus (hbv) genome was amplified and sequenced from samples taken from one animal. this indicates that hbv is distributed across the entire range of chimpanzee habitats.200212368360
expression of a new woodchuck ifn-alpha gene by a helper-dependent adenoviral vector in woodchuck hepatitis virus-infected primary hepatocytes.recombinant interferon-alpha (rifn-alpha) is currently used in the treatment of viral hepatitis either alone or in combination with small molecules. however, this treatment is not very efficacious, and more effective protocols are needed. to this end, we have explored the woodchuck hepatitis system, validated as an infection model for vaccination and antiviral studies against human hepatitis b virus (hbv) infection. the lack of a woodchuck ifn-alpha (woifn-alpha) homolog has prevented study of v ...200212433282
out-of-frame versus in-frame core internal deletion variants of human and woodchuck hepatitis b viruses.human hepatitis b virus (hbv) variants containing in-frame core internal deletion (cid) have been demonstrated to contain all the functional features of defective interfering (di) particles (yuan, t. t.-t., m.-h. lin, d. s. chen, and c. shih, 1998, j. virol. 72, 578-584). here, we report that out-of-frame hbv cid variants exhibit defective interfering property similar to in-frame cid variants characterized previously. this result raises the possibility that it may be the deleted pregenomic rna p ...200211878906
viral pharmacodynamic model for (-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine (emtricitabine) in chronically infected woodchucks.there is a need for adequate models of virus depletion in animals and humans as a function of drug dose in order to plan starting dose regimens in the clinic for new antiretroviral nucleoside agents. an indirect response pharmacodynamic model was fitted to link the plasma pharmacokinetics from a 28 day treatment with the nucleoside reverse transcription inhibitor emtricitabine [(-)-ftc], with the resulting virus depletion and recovery profiles in woodchucks chronically infected with woodchuck he ...200212448689
comparison of cell culture systems for duck hepatitis b virus using sybr green quantitative pcr.the hepadnaviridae family contains dna viruses such as human hepatitis b virus (hbv), woodchuck hepatitis b virus (whv), and duck hepatitis b virus (dhbv). dhbv is distributed in both wild and domestic ducks. hbv is a worldwide health problem with carriers at risk of developing cirrhosis and liver cancer. all medical staff and scientists working with hbv must be vaccinated, because of its highly contagious nature. dhbv is a safe surrogate for hbv because of their similarities. several cell cultu ...200212393148
detection of a unique genotype of monkey b virus (cercopithecine herpesvirus 1) indigenous to native japanese macaques (macaca fuscata).the japanese macaque or snow monkey (macaca fuscata) is an autochthonous monkey in japan. it has long been assumed that the monkey population was not infected with cercopithecine herpesvirus 1 (monkey b virus [bv]) since cases of human bv infection have never been reported in japan. although serologic testing of captive snow monkeys in japan revealed antibodies to bv, it was thought that native japanese macaques had either been infected with herpes simplex virus from humans or with bv from other ...200212540170
avian and mammalian hepadnaviruses have distinct transcription factor requirements for viral replication.hepadnavirus replication occurs in hepatocytes in vivo and in hepatoma cell lines in cell culture. hepatitis b virus (hbv) replication can occur in nonhepatoma cells when pregenomic rna synthesis from viral dna is activated by the expression of the nuclear hormone receptors hepatocyte nuclear factor 4 (hnf4) and the retinoid x receptor alpha (rxr alpha) plus peroxisome proliferator-activated receptor alpha (ppar alpha) heterodimer. nuclear hormone receptor-dependent hbv replication is inhibited ...200212097559
ospe-related, ospf-related, and elp lipoproteins are immunogenic in baboons experimentally infected with borrelia burgdorferi and in human lyme disease patients.presently, the rhesus macaque is the only nonhuman primate animal model utilized for the study of lyme disease. while this animal model closely mimics human disease, rhesus macaques can harbor the herpes b virus, which is often lethal to humans; macaques also do not express the full complement of immunoglobulin g (igg) subclasses found in humans. conversely, baboons contain the full complement of igg subclasses and do not harbor the herpes b virus. for these reasons, baboons have been increasing ...200212409407
in vivo transmission and dynamics of deleted genomes after experimental infection of woodchuck hepatitis b virus in adult animals.the presence of deleted genomes has been shown in a number of viral models including hepadnaviridae. the analysis of woodchuck hepatitis b virus (whv) population after experimental infection of woodchuck 197 (w197) with whv7-pi inoculum revealed the presence of two deleted genomes: dg600 lacking a 1330 bp region (core/polymerase/pres1) and dg900 showing a deletion of 869 nts (pol/pres/s). these mutants were also present in whv7-pi. the successive whv experimental infections in adult animals were ...200212416678
helicobacter marmotae sp. nov. isolated from livers of woodchucks and intestines of cats.woodchucks (marmota monax) have a high incidence of hepatocellular carcinoma (hcc) associated with chronic infection with woodchuck hepatitis virus (whv) and serve as a model of hepatitis b virus-associated hcc in humans. helicobacter hepaticus, an enterohepatic helicobacter in mice, is known to cause hepatocellular adenomas and carcinomas in susceptible mouse strains. in long-term chemical bioassays conducted with b6c3f(1) mice, h. hepaticus has been regarded as a confounding factor because of ...200212089272
woodchuck gamma interferon upregulates major histocompatibility complex class i transcription but is unable to deplete woodchuck hepatitis virus replication intermediates and rnas in persistently infected woodchuck primary hepatocytes.gamma interferon (ifn-gamma) is an important mediator with multiple functions in the host defense against viral infection. ifn-gamma, in concert with tumor necrosis factor alpha (tnf-alpha), leads to a remarkable reduction of intrahepatic replication intermediates and specific mrnas of hepatitis b virus (hbv) by a noncytolytic mechanism in the transgenic mouse model. thus, it is rational to evaluate the potential value of ifn-gamma for the treatment of chronic hbv infection. in the present study ...200211739671
a pregenomic rna sequence adjacent to dr1 and complementary to epsilon influences hepatitis b virus replication efficiency.hepatitis b virus (hbv) possesses a 3.2-kb partially double-stranded dna genome that is generated inside the nucleocapsid by the reverse transcription of the 3.5-kb pregenomic viral transcript. the initial steps in viral replication involve the recognition of an encapsidation signal termed epsilon (epsilon) at the 5'-end of the pregenomic rna by the hbv polymerase. the polymerase-bound pregenomic rna is subsequently incorporated into an immature nucleocapsid particle and minus-strand hbv dna syn ...200212482672
serological evidence of transmission of human influenza a and b viruses to caspian seals (phoca caspica).seroepidemiological surveillance of influenza in caspian seals (phoca caspica) was conducted. antibodies to influenza a virus were detected in 54% (7/13), 57% (4/7), 40% (6/15) and 26% (11/42) of the serum samples collected in 1993, 1997, 1998 and 2000 by enzyme-linked immunosorbent assay (elisa). in an hemagglutination-inhibition (hi) test using h1-h15 reference influenza a viruses as antigens, more than half of the examined elisa-positive sera reacted with an h3n2 prototype strain a/aichi/2/68 ...200212437032
hepatitis b and c viruses infection, lifestyle and genetic polymorphisms as risk factors for hepatocellular carcinoma in haimen, china.a case-control study was carried out to investigate the impact of factors including virus infection, aflatoxin b1, microcystins, smoking/drinking and dietary habits as well as genetic polymorphisms of aldehyde dehydrogenase 2 (aldh2) and cytochrome p4502e1 (cyp2e1), on susceptibility to hepatocellular carcinoma (hcc) in haimen, china. a total of 248 patients with hcc and 248 sex-, age- and residence-matched population-based controls were recruited into the study. virus infection, and aldh2 and c ...200212495467
detection of virus-like particles in the liver of black and white ruffed lemurs with hepatitis.two young black and white ruffed lemurs (varecia variegata variegata) died at the san diego zoo (san diego, california, usa) with extensive liver lesions suggestive of acute viral infection. immunoassays performed to detect hepatitis b virus (hbv) markers were negative. polymerase chain reaction (pcr) primers overlapping the hbv core gene produced an amplicon of approximately 411 base pairs (bp) from serum dna of a hbv-positive western lowland gorilla (gorilla gorilla gorilla) but not from serum ...200212038123
turnover of hepatitis b virus x protein is regulated by damaged dna-binding complex.mammalian hepatitis b viruses encode an essential regulatory protein, termed x, which may also be implicated in liver cancer development associated with chronic infection. x protein, also referred to as hbx in human virus and whx in woodchuck virus, has been reported to bind to a number of cellular proteins, including the ddb1 subunit of the damaged dna-binding (ddb) complex. our previous work provided genetic evidence for the importance of whx-ddb1 interaction in both the activity of the x prot ...200212050362
real-time polymerase chain reaction assays for leukocyte cd and cytokine mrnas of the eastern woodchuck (marmota monax).real-time polymerase chain reaction (pcr) assays were developed for woodchuck leukocyte cluster of differentiation (cd) and cytokine mrna expression. plasmid dna standards of each marker (cd3, cd4, cd8, il-2, ifn-gamma, tnf-alpha, il-4, il-10), and rna standards from mitogen-stimulated woodchuck peripheral blood mononuclear cells (pbmcs) were used to validate and optimize the assays for taqman 7700 and icycler pcr instruments. the complementary dnas (cdnas) produced by reverse transcription (rt) ...200212052347
efficacy of a b virus gd dna vaccine for induction of humoral and cellular immune responses in japanese macaques.it is desirable to prevent dissemination of b virus (bv) in macaque colonies because transmission of bv to humans causes deadly encephalomyelitis. vaccination of monkeys is one method that could confine spread of bv within macaque colonies. availability of a bv dna vaccine for use in macaques would eliminate the risk of working with infectious bv. toward this end, we constructed a plasmid expressing the bv glycoprotein d (gd). immunogenicity of this construct as a dna vaccine was assessed in adu ...200212057608
a new model of hepatitis b virus reinfection: liver transplantation in the woodchuck1.reinfection of liver grafts with hepatitis b virus (hbv) is a pertinent problem in clinical liver transplantation, requiring the development of new treatment strategies. however, no animal model is currently available to study the course and mechanism of hepatitis b reinfection. this was the reason to establish the technique of liver transplantation in the woodchuck, which is a widely used animal model for hbv infection.200212177617
serological evidence of alpha herpesvirus infection in sooty mangabeys.contact between sooty mangabeys (sms) and a pigtailed macaque prompted the serological screening of sms for evidence of infection with b virus. serological tests detected sm antibodies that reacted with b virus polypeptides. additional testing was performed with sera from sms with no previous contact with macaques. results from these tests indicated that 56% (33/59) of the sms had antibodies that reacted with b virus and sa8. sm antibodies also reacted with herpesvirus papio 2 and to a lesser ex ...200212190852
hepatitis viruses: a pandora's box?the term hepatitis virus is reserved for those viruses that are predominantly hepatotropic, although several new agents have been assigned to this category in the absence of hepatotropism and clinical disease. the hepatitis viruses can be broadly divided into those transmitted via the fecal-oral route, and those by blood, blood products and body fluids. hepatitis a (picornaviridae), hepatitis b (hepadnaviridae) and hepatitis c (flaviviridae) represent the major public health problems. the epidem ...200212534779
immunogenic effects of woodchuck hepatitis virus surface antigen vaccine in combination with antiviral therapy: breaking of humoral and cellular immune tolerance in chronic woodchuck hepatitis virus infection.a rational treatment strategy for chronic hepatitis b virus (hbv) infection might involve the modulation of immunity after the reduction of viremia and antigenemia. this strategy was tested in woodchucks chronically infected with the woodchuck hepatitis virus (whv) by combining antiviral treatment with 1-(2-fluoro-5-methyl-beta-l-arabinofuranosyl)-uracil (l-fmau) and therapeutic vaccination with whv surface antigen (whsag).200212566706
in vitro expression of human hepatitis b virus genomes carrying woodchuck hepatitis virus pre-s1 sequences.many hepatitis b virus (hbv) in vivo experiments are unfeasible because this virus infects only humans. former studies demonstrated that the pre-s1 domain of the viral envelope protein l determines host range. therefore, we tried to generate hbv recombinants which might be able to infect woodchucks by exchanging different portions of the pre-s1 encoding gene with homologous parts from the related woodchuck hepatitis virus (whv) in a cloned hbv genome. in 6 mutants, 11-92 n-terminal hbv pre-s1 co ...200212566705
detection and species-level identification of primate herpesviruses with a comprehensive pcr test for human herpesviruses.a comprehensive assay for the identification of all eight human herpesviruses has been previously reported. this assay was extended to the detection and species-level identification of herpes b virus (cercopithecine herpesvirus 1) and african green monkey cytomegalovirus (cercopithecine herpesvirus 5), two herpesviruses of relevance to the clinical virology laboratory.200312624061
the efficiency of humoral immune transfer depends on both the graft and the immunosuppressive treatment.the present study was designed to compare the efficiency of adoptive transfer of humoral immunity after liver, kidney, and heart transplantation in relation to the number of passenger lymphocytes, and to estimate the risk of a detrimental effect and the chance of a beneficial effect. hepatitis b virus surface-antigen-vaccinated brown norway rats (bns) and axc 9935 irish (aci rats) served as donors, and naïve lewis (lew) rats as recipients. the liver grafts contained 100 times more passenger lymp ...200312664210
role of type 1 versus type 2 immune responses in liver during the onset of chronic woodchuck hepatitis virus infection.immune response messenger rnas (mrna) were compared in liver during self-limited (resolved) and chronic neonatal woodchuck hepatitis virus (whv) infection. at week 14 postinfection (mid-acute phase), mrnas for leukocyte markers (cd3, cd4, cd8), type 1 cytokines and related transcription factors (ifn-gamma, tnf-alpha, stat4, t-bet), and il-10 were increased in livers from resolving infections, but mrnas of other type 1 (il-2) and type 2 (il-4, stat6, and gata3 markers remained at baseline levels. ...200312668969
prevalence of antibodies to selected viruses in a long-term closed breeding colony of rhesus macaques (macaca mulatta) in brazil.the rhesus macaque breeding colony of the oswaldo cruz foundation (fiocruz) was established in 1932 from a founding stock of 100 animals. this population has remained closed to new animal introductions for almost 70 years. a serologic survey was performed to determine the prevalence of antibodies to selected viruses as a first approach to identifying viral pathogens endemic in this population. banked serum samples were tested for antibodies to simian immunodeficiency virus (siv), simian t-lympho ...200312619046
replication and transmission of influenza viruses in japanese quail.quail have emerged as a potential intermediate host in the spread of avian influenza a viruses in poultry in hong kong. to better understand this possible role, we tested the replication and transmission in quail of influenza a viruses of all 15 ha subtypes. quail supported the replication of at least 14 subtypes. influenza a viruses replicated predominantly in the respiratory tract. transmission experiments suggested that perpetuation of avian influenza viruses in quail requires adaptation. swi ...200312788625
inactivated parapoxvirus ovis (orf virus) has antiviral activity against hepatitis b virus and herpes simplex virus.it is known that some viruses are able to induce vigorous immune reactions. this study shows that inactivated parapoxvirus ovis (orf virus), strain d1701 (ppvo), induces an autoregulatory cytokine response that involves the upregulation of il-12, il-18, ifn-gamma and other t helper 1-type cytokines and their subsequent downregulation, which is accompanied by induction of il-4. an increase in il-10 expression was also found in the livers of ppvo-treated mice. ppvo protects mice from lethal herpes ...200312810878
activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the hbx protein involved in hepatitis b virus replication.human hepatitis b virus (hbv) hbx protein is a multifunctional protein that activates cellular signaling pathways and is thought to be essential for viral infection. woodchuck hbv mutants that lack hbx are unable to replicate in vivo or are severely impaired. hbv replication in hepg2 cells, a human hepatoblastoma cell line, is stimulated 5- to 10-fold by hbx protein. we have utilized the hepg2, hbx-dependent hbv replication system to study the effects of activators and inhibitors of cytosolic ca ...200312829810
geographic and species association of hepatitis b virus genotypes in non-human primates.infection with hepatitis b virus (hbv) has been detected in human populations throughout the world, as well as in a number of ape species (pan troglodytes, gorilla gorilla, gibbons [nomascus and hylobates species] and pongo pygmaeus). to investigate the distribution of naturally occurring hbv infection in these species and other african old world monkey species (cercopithecidae), we screened 137 plasma samples from mainly wild caught animals by polymerase chain reaction (pcr) using several of hi ...200314517090
[differentially expressed genes in hepatocellular carcinoma of tree shrew induced by different factors].previous studies on differentially expressed genes in hepatocellular carcinoma (hcc) used to perform with para-cancerous tissues as normal control. however, the para-cancerous tissue of hcc is actually abnormal because they frequently contain hepatitis, cirrhosis, hyperplastic nodules or foci, etc. in order to explore the molecular mechanism and the responsible genes for hepatocarcinogenesis, through applying the hcc model of tree shrew (tupaia belangeri chinensis), this study was designed to co ...200314558942
hepatic cirrhosis occurring in a young woodchuck (marmota monax) due to vertical transmission of woodchuck hepatitis virus (whv).histologic and clinicopathologic findings of a woodchuck (marmota monax) vertically infected with woodchuck hepatitis virus (whv) are presented. the liver exhibits marked cirrhotic changes, which is characteristic of the pre-transformation phase of whv. at necropsy, the woodchuck exhibited ascites and the liver had a grossly nodular appearance. microscopically, focal hepatocyte necrosis and inflammatory cells were observed in midzonal and periportal areas in the liver. in macchiavellos stained s ...200314610377
complete nucleotide sequence and phylogenetic analyses of hepatitis b virus isolated from two pileated gibbons.we analyzed full-length sequence of hepatitis b virus (hbv) recovered from two pileated gibbons (hylobates pileatus) originally born in east asia. two animals possessed a viral genome of 3182 nt in length with a 33 nt deletion in the pre-s1 region, and designated hbv pg-makiko and hbv pg-yohko, respectively. both sequences had 65-90% similarity to type a-g of human hbv isolates. phylogenetic analysis demonstrated that both isolates were distinct from the human and other nonhuman primate hbv isol ...200314618082
alteration of the p53 gene during tree shrews' hepatocarcinogenesis.to detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis b virus (hbv) and aflatoxin b1 (afb1).200314627531
inhibitory effect of adefovir and lamivudine on the initiation of hepatitis b virus infection in primary tupaia hepatocytes.adefovir dipivoxil and lamivudine are two safe and efficacious drugs licensed for the treatment of chronic hepatitis b virus (hbv) infection. both drugs inhibit the viral polymerase, resulting in a profound suppression of virus production. blocking the viral polymerase may also affect the initiation of hbv infection, because hbv virions harbor a partially double-stranded genome and productive infection requires completion of viral plus-strand dna synthesis with subsequent formation of covalently ...200314647052
comparison of tamarins and marmosets as hosts for gbv-b infections and the effect of immunosuppression on duration of viremia.gbv-b virus is a close relative to hepatitis c virus (hcv) that causes hepatitis in tamarins, and thus, is an attractive surrogate model for hcv. in this study, we demonstrate that the host range of gbv-b extends to the common marmoset with an infection profile similar to that observed for tamarins. marmoset hepatocytes were susceptible to in vitro infection with gbv-b. virus was efficiently secreted into the medium, and approximately 25% of hepatocytes were positive for ns3 staining. in an atte ...200312832204
follow up of infection of chacma baboons with inoculum containing a and non-a genotypes of hepatitis b virus.to determine whether one genotype (a or non-a genotypes of hbv) predominated over the other during the course of hbv infection.200312679921
[alteration of p53 gene during tree shrews' hepatocarcinogenesis].to detect the expression and variation of p53 gene during tree shrews' hepatocarcinogenesis induced by hepatitis b virus (hbv) and aflatoxin b1 (afb1).200312681064
molecular genetic and biochemical analysis of woodchuck (marmota monax) mhc class i polymorphism.the woodchuck (marmota monax) is an animal model that is used in the study of human hepatitis b virus ( hbv ) infection. a knowledge of woodchuck mhc class i (mamo-i) genes and gene products is therefore essential for understanding the antigen-specific t-cell responses in this animal model. a number of mamo-i genes have been identified by molecular cloning and sequencing. however, the allelic nature of these genes has not been proven by classical genetics like the segregation analysis in familie ...200312694573
universal primers for real-time amplification of dna from all known orthohepadnavirus species.the family of hepadnaviridae is made up of members infecting birds (genus avihepadnavirus) or mammals (genus orthohepadnavirus). hepatitis b virus (hbv), the hepadnavirus infecting humans, can be divided into the seven genotypes a-g. by definition, genotypes differ by more than 8% at the nucleotide level. however, some genotypes differ by more than 14% from others.200312727526
overexpression of hepatitis b virus surface antigens including the pres1 region in a serum-free chinese hamster ovary cell line.current hepatitis b virus (hbv) vaccines consist of preparations of recombinant hbv major surface antigen (sag) and are protective in about 90-95% of vaccinated subjects. in improved vaccines, the frequency of nonresponders to the classical vaccine could be reduced by including additional epitopes from the pres-domains of the middle and large surface antigens. in this report, the development and characterization of a cho cell line for hbsag, expressing major, middle, and large antigens are descr ...200312729726
complete sequence and comparative analysis of the genome of herpes b virus (cercopithecine herpesvirus 1) from a rhesus monkey.the complete dna sequence of herpes b virus (cercopithecine herpesvirus 1) strain e2490, isolated from a rhesus macaque, was determined. the total genome length is 156,789 bp, with 74.5% g+c composition and overall genome organization characteristic of alphaherpesviruses. the first and last residues of the genome were defined by sequencing the cloned genomic termini. there were six origins of dna replication in the genome due to tandem duplication of both oril and oris regions. seventy-four gene ...200312743273
ultrasonography in the study of hepatocellular carcinoma in woodchucks chronically infected with whv.the woodchuck hepatitis virus (whv)/woodchuck system is studied as animal model of human hepatocellular carcinoma (hcc) induced by chronic hepatitis b virus infection. the aim of the present study was the evaluation of ultrasound (us) liver examination in woodchuck as a routine method to detect hcc nodules and to follow their growth. sixteen woodchucks were included in the study. us liver examination was carried out in all animals using a 5 mhz convex scanner. macroscopic and microscopic examina ...200312869286
[human hepatitis b virus infection of tree shrews and macaca assamensis in vivo].to examine sensitivity of the tree shrews and macaca assamensis to human hepatitis b virus (hhbv) by serologic methods.200312884835
antiviral activity and pharmacokinetics of 1-(2,3-dideoxy-2-fluoro-beta-l-glyceropent-2-enofuranosyl)cytosine.1-(2,3-dideoxy-2-fluoro-beta-l-glyceropent-2-enofuranosyl)cytosine (l-2'-fd4c) is an l-nucleoside analogue with both anti-human immunodeficiency virus (hiv) and anti-hepatitis b virus (hbv) activity with median effective concentrations of 0.12 microm in peripheral blood mononuclear cells and 0.002 microm in hepg2-2.2.15 cells, respectively. the purpose of this study was to examine the antihepadnavirus potency and pharmacokinetics of l-2'-fd4c in vivo. hbv-transgenic mice treated intraperitoneall ...200312760868
pre-s1 antigen-dependent infection of tupaia hepatocyte cultures with human hepatitis b virus.the susceptibility of the tree shrew tupaia belangeri to human hepatitis b virus (hbv) has been demonstrated both in vivo and in vitro. in this study, we show that purified hbv infects primary t. belangeri hepatocyte cultures in a very specific manner, as detected by hbv covalently closed circular dna, mrna, hbv e antigen, and hbsag production. a monoclonal antibody (mab), ma18/7, directed against the pre-s1 domain of the large hbs protein, which has been shown to neutralize infectivity of hbv f ...200312915565
induction of antibodies to the pres region of surface antigens of woodchuck hepatitis virus (whv) in chronic carrier woodchucks by immunizations with whv surface antigens.one goal of therapeutic vaccinations against chronic hepatitis b virus infection is to stimulate the b-cell responses to viral surface antigens in chronic carriers. here we investigated the induction of antibody responses to hepadnaviral surface antigens in the woodchuck model, with emphasis on the vaccination of woodchucks chronically infected with woodchuck hepatitis virus (whv).200312927927
molecular characterization of cd28 and cytotoxic t-lymphocyte-associated antigen 4 (ctla-4) of woodchuck (marmota monax).eastern woodchuck (marmota monax) became an important animal model to study the immunological processes in hepatitis b virus infection. to facilitate further study of t-cell responses in this model, we cloned and sequenced the cdnas of woodchuck cd28 and cytotoxic t-lymphocyte-associated antigen 4 (ctla-4), which play important roles for the regulation of t-cell activation by delivering the costimulation signals. according to the deduced amino-acid sequences, woodchuck cd28 showed a similarity o ...200312956876
fatal herpes simplex infection in a group of common marmosets (callithrix jacchus).an outbreak of classical herpetic infection causing vesicoulcerative stomatitis in a family group (eight animals) of callithrix jacchus is described. in all eight infected animals, human herpesvirus 1 (hhv-1) was identified as the causative agent. this was confirmed by histologic, immunohistologic, and molecular biologic investigations, as well as by virus isolation. the clinical picture, the macroscopic appearance, and the histologic results indicated a herpes infection as the cause of mortalit ...200312824512
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