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genomic dna double-strand breaks are targets for hepadnaviral dna integration.integrated hepadnaviral dna in livers and tumors of chronic hepatitis b patients has been reported for many years. in this study, we investigated whether hepatitis b virus dna integration occurs preferentially at sites of cell dna damage. a single i-scei homing endonuclease recognition site was introduced into the dna of the chicken hepatoma cell line lmh by stable dna transfection, and double-strand breaks were induced by transient expression of i-scei after transfection of an i-scei expression ...200415258290
suppression of lamivudine-resistant b-domain mutants by adefovir dipivoxil in the woodchuck hepatitis virus model.adult woodchucks (marmota monax) chronically infected with woodchuck hepatitis virus (whv) were treated orally with lamivudine (15 mg/kg per day) for 57 weeks. after 20 weeks of treatment a 2-3 log reduction in serum whv dna was detected. serum titers of whv then increased gradually, in the presence of lamivudine treatment, reaching pre-treatment values by week 40. viral recrudescence was associated with development of mutations in the b domain of the whv polymerase gene. mutations observed in t ...200415302140
adenovirus-based gene therapy during clevudine treatment of woodchucks chronically infected with woodchuck hepatitis virus.interferon-alpha (ifn-alpha) is a potent suppressor of hepatitis b virus (hbv) replication in the hbv-transgenic mouse, depleting virus replication intermediates from infected hepatocytes via pathways mediated by interferon-gamma (ifn-gamma) and tumor necrosis factor alpha (tnf-alpha). it has also been hypothesized that cytokines induce curing of infected hepatocytes via non-cytolytic pathways during resolution of transient hepadnavirus infections. we have therefore evaluated therapy of chronic ...200415327895
antigenic alteration of influenza b virus associated with loss of a glycosylation site due to host-cell adaptation.effects of host-cell adaptation of the hemagglutinin (ha) protein were evaluated by the analyses of four pairs of recent influenza b field isolates, each pair consisting of an madin darby canine kidney (mdck)- and an embryonated chicken egg-derived isolates from the same clinical specimen. among the isolates examined, all of the mdck-derived isolates retained glycosylation site at amino acid 197 on the ha1 molecule, whereas three egg-derived isolates lost it. antigenic difference in the ha molec ...200415332284
[serial pathologic changes in livers of tree shrews and macaca assamensises infected with human hepatitis b virus].to serially observe the pathologic changes in livers of tree shrews and macaca assamensises infected with hhbv.200315340568
a dose-finding study of once-daily oral telbivudine in hbeag-positive patients with chronic hepatitis b virus infection.current therapy for chronic hepatitis b is suboptimal as a result of limited durable response rates, cumulative viral resistance, and/or poor tolerability. telbivudine has potent antiviral activity against hepatitis b virus (hbv) in vitro and in the woodchuck model and has a promising preclinical safety profile. in this first clinical study of telbivudine, safety, antiviral activity, and pharmacokinetics were assessed in 43 adults with hepatitis b e antigen-positive chronic hepatitis b. this pla ...200415349912
persistence of isolated antibodies to woodchuck hepatitis virus core antigen is indicative of occult infection.antibodies against virus nucleocapsid (anticore) normally accompany hepadnaviral hepatitis but they may also occur in the absence of symptoms and other serological indicators of the infection. this situation can be encountered following a clinically and serologically unapparent exposure to hepatitis b virus (hbv) or after recovery from hepatitis b. in this study, woodchucks inoculated with woodchuck hepatitis virus (whv) were investigated to determine the relationship between anticore detection ...200415382154
the win locus involved in activation of the distal n-myc2 gene upon whv integration in woodchuck liver tumors harbors s/mar elements.woodchuck hepatitis virus (whv) and the woodchuck (marmota monax) are models for hepatocellular carcinoma (hcc) induced by hepatitis b virus (hbv). in woodchuck liver tumors, the n-myc2 proto-oncogene is frequently activated by whv integration either close to the gene or in the b3n and win downstream loci, located 10 and 150 kb from n-myc2, respectively. a scaffold/matrix attachment region (s/mar) regulative element was shown to be in b3n, possibly mediating activation of the upstream n-myc2 gen ...200415476869
a natural asymptomatic herpes b virus infection in a colony of laboratory brown capuchin monkeys (cebus apella).herpes b virus (bv) infection of macaques persists in the natural host, but is mainly asymptomatic. however, bv can cause fatal disease in humans and in several non-macaque species such as capuchin monkeys (cebus apella). the bv infection described here in a colony of capuchin monkeys was persistent but asymptomatic. initially the infection was detected serologically in five out of seven animals. however, using polymerase chain reaction (pcr) developed specifically for bv, we found the virus in ...200415479559
hepatocellular carcinoma in the woodchuck model of hepatitis b virus infection.the eastern woodchuck ( marmota monax ) harbors a dna virus (woodchuck hepatitis virus [whv]) that is similar in structure and replicative life cycle to the human hepatitis b virus (hbv). like hbv, whv infects the liver and can cause acute and chronic hepatitis. furthermore, chronic whv infection in woodchucks usually leads to development of hepatocellular carcinoma (hcc) within the first 2-4 years of life. the woodchuck model has been important in the preclinical evaluation of safety and effica ...200415508096
viral infection following kidney transplantation: long-term follow-up in a single center.viral infections are a leading cause of posttransplantation morbidity and mortality. the use of more potent immunosuppressive agents is responsible in part for the increasing incidence of some viral infections. this study summarized our experience with viral infections in 561 kidney transplant recipients.200415518767
woodchuck interleukin-6 gene: structure, characterization, and biologic activity.woodchuck is an important animal model for studying human hepatitis b virus (hbv) infection. within the cytokine network, interleukin-6 (il-6) plays an important role in immune responses that may lead to viral clearance. to further understand woodchuck il-6 biology, we cloned and characterized the il-6 gene from white blood cells. the complete woodchuck il-6 gene is about 7 kb and consists of five exons and four introns. the il-6 gene organization of the woodchuck is similar to those of the huma ...200415527975
alteration of p53 and p21 during hepatocarcinogenesis in tree shrews.to investigate p53 mutation and p21 expression in hepatocarcinogenesis induced by hepatitis b virus (hbv) and aflatoxin b(1) (afb(1)) in tree shrews, and to reveal the role of these genes in hepatocarcinogenesis.200415534906
phosphorylation analysis of 90 kda heat shock protein within the cytosolic arylhydrocarbon receptor complex.the arylhydrocarbon receptor (ahr) functions as a ligand-activated transcription factor that regulates the transcription of genes encoding xenobiotic metabolizing enzymes and also mediates most of the toxic effects caused by dioxins and polycyclic aromatic hydrocarbons. the cytosolic ahr complex exists as a transcriptionally cryptic complex, consisting of the 90 kda heat shock protein (hsp90) and the hepatitis b virus x-associated protein 2 (xap2). the posttranslational modifications, especially ...200415581363
[in vitro expression of wild type and precore mutant woodchuck hepatitis virus].hepatitis b virus (hbv) precore 1896 and 1898 g-->a mutations are regarded as hot spots to study. such mutants have been considered associating with molecular and biological changes of hbv and causing chronic hepatitis and severe forms of hepatitis, including fulminant hepatitis. using oligonucleotide-directed mutagenesis, we have conducted the same point mutations in the precore gene of an infectious clone of woodchuck hepatitis virus (whv-8). transfection of mutant whv dna, 1896 mutant (whv-m1 ...199715619810
chronic infection with hepatitis b viruses and antiviral drug evaluation in upa mice after liver repopulation with tupaia hepatocytes.transplantation of primary human hepatocytes and establishment of hepatitis b virus (hbv) infection in immunodeficient urokinase plasminogen activator (upa) transgenic mice was shown. however, the availability of usable primary human hepatocytes is very limited. therefore, alternative and more accessible sources of hepatocytes permissive for hbv infection are highly desirable. here we investigated the potential of primary hepatocytes from the tree shrew tupaia belangeri that were shown to be sus ...200515629507
use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans.chronic infection with hepatitis b virus (hbv) is associated with the majority of hepatocellular carcinoma (hcc). the diagnosis of hcc is usually made in the late stages of the disease, when treatment options are limited and prognosis is poor. we therefore have developed a method of glycoproteomic analysis in an attempt to discover serum markers that can assist in the early detection of hbv-induced liver cancer. briefly, a comparative method for analysis of oligosaccharides released from serum g ...200515642945
clevudine therapy with vaccine inhibits progression of chronic hepatitis and delays onset of hepatocellular carcinoma in chronic woodchuck hepatitis virus infection.we examined a rational approach to therapy of chronic hepatitis b virus (hbv) infection that utilized the reduction of viral load combined with appropriately timed immune modulation/stimulation. in a placebo-controlled study, chronic woodchuck hepatitis virus (whv) carrier woodchucks received clevudine (l-fmau), previously shown to have especially potent and sustained antiviral activity in woodchucks, for 32 weeks followed by whv surface antigen (whsag) alum-adjuvanted vaccine at 32, 36, 40 and ...200415651753
frequent infection of hylobates pileatus (pileated gibbon) with species-associated variants of hepatitis b virus in cambodia.as well as being distributed widely in human populations, hepatitis b virus (hbv) infections occur frequently in chimpanzee, gibbon and other ape populations in sub-saharan africa and south-east asia. to investigate the frequency and genetic relationships of hbv infecting gibbons in cambodia, pileated gibbons (hylobates pileatus) that were originally wild-caught were screened for surface antigen. twelve of 26 (46 %) were positive, of which 11 were positive for hbv dna. phylogenetic analysis of c ...200515659752
hepatitis b virus mutations associated with fulminant hepatitis induce apoptosis in primary tupaia hepatocytes.hepatitis b virus (hbv) core promoter mutations have been implicated in the pathogenesis of fulminant hepatitis b. due to the limited availability of primary human hepatocytes, the functional characterization of hbv mutants has been performed predominantly in transformed cells, which may not represent ideal model systems for studying virus-cell interactions. we and others have shown that primary hepatocytes of the tree shrew tupaia belangeri support hbv infection and replication. in this study, ...200515660384
herpes b-virus seroreactivity in a colony of macaca mulatta: data from the sabana seca field station, a new specific pathogen-free program.the demand for b-virus-free animals for biomedical research is increasing, while at the same time the availability of such animals is decreasing. the establishment of specific pathogen-free (spf) breeding macaque colonies is a priority of the national institutes of health. nevertheless, it is well known that seroreactivity to b-virus can be difficult to interpret, particularly as it can vary over time in a single animal. the aim of the present study was to implement a reliable algorithm to exami ...200515667339
pharmacokinetics of the antiviral agent beta-l-3'-fluoro-2',3'-didehydro-2',3'-dideoxycytidine in rhesus monkeys.beta-l-3'-fluoro-2',3'-didehydro-2',3'-dideoxycytidine (l-3'-fd4c) is a potent and selective antiretroviral nucleoside with activity against lamivudine-resistant human immunodeficiency virus type 1 (hiv-1) and hepatitis b virus (hbv) in vitro. the pharmacokinetics of l-3'-fd4c were characterized in three rhesus monkeys given single intravenous and oral doses. a two-compartment open model was fitted to the plasma and urine data. plasma concentrations declined in a biexponential fashion with an av ...200515673733
korean medicinal plant extracts exhibit antiviral potency against viral hepatitis.investigation of natural ethnopharmacologic extracts exhibiting antiviral potential may lead to the discovery of new therapeutics for the treatment of chronic viral hepatitis infections. traditional korean medicinal herbs have been identified that exhibit potency against hepatitis b virus (hbv) and hepatitis c virus (hcv) infections. research on the antiviral potential of naturally derived extracts is facilitated through the use of appropriate animal and liver cell culture models for these hepat ...200415673997
identification and characterization of avihepadnaviruses isolated from exotic anseriformes maintained in captivity.five new hepadnaviruses were cloned from exotic ducks and geese, including the chiloe wigeon, mandarin duck, puna teal, orinoco sheldgoose, and ashy-headed sheldgoose. sequence comparisons revealed that all but the mandarin duck viruses were closely related to existing isolates of duck hepatitis b virus (dhbv), while mandarin duck virus clones were closely related to ross goose hepatitis b virus. nonetheless, the s protein, core protein, and functional domains of the pol protein were highly cons ...200515708992
re-analysis of a human hepatitis b virus (hbv) isolate from an east african wild born pan troglodytes schweinfurthii: evidence for interspecies recombination between hbv infecting chimpanzee and human.according to current estimates, hepatitis b virus (hbv) has infected 2 billion people worldwide and among them, 360 million suffer from chronic hbv infection. except humans, hbv or hbv-like viruses have also been isolated from different species of apes and mammals. although recombination has been described to occur extensively between different genotypes within the human hbv lineage, no recombination event has ever been reported between human and non-human primate hbv sequences. it was our objec ...200515777724
the tree shrews: useful animal models for the viral hepatitis and hepatocellular carcinoma.hepatitis b virus (hbv)-induced hepatitis and hepatocellular carcinoma (hcc) are major diseases worldwide. hbv infection and chemical carcinogens such as aflatoxin b1 are known to be two key factors in the development of hcc. animal models for hepatitis and hcc are very useful in the in vivo studies of mechanism involved in the development and prevention of these diseases and the pre-clinical research of drugs for the treatment of these diseases. now, several animals, such as woodchucks, ground ...200515816489
dimeric zanamivir conjugates with various linking groups are potent, long-lasting inhibitors of influenza neuraminidase including h5n1 avian influenza.the synthesis, antiviral and pharmacokinetic properties of zanamivir (zmv) dimers 8 and 13 are described. the compounds are highly potent neuraminidase (na) inhibitors which, along with dimer 3, are being investigated as potential second generation inhaled therapies both for the treatment of influenza and for prophylactic use. they show outstanding activity in a 1 week mouse influenza prophylaxis assay, and compared with zmv, high concentrations of 8 and 13 are found in rat lung tissue after 1 w ...200515828835
characterization of duck leucocytes by monoclonal antibodies.cdnas encoding cd3epsilon, cd4 and the alpha-chain of cd8 of ducks were cloned. monoclonal antibodies against pekin duck cd4 and cd8alpha revealed that the antigens were expressed by the majority of thymocytes and by subpopulations of cd3+ cells in peripheral tissues. cd8alpha cell surface expression was also found on 90% of bursal cells. the b cell specificity of a newly developed mab to the immunoglobulin light-chain (l-chain) was confirmed by double labelling studies with the chicken b-cell c ...200515854685
a pre-s/s cho-derived hepatitis b virus vaccine protects woodchucks from whv productive infection.we evaluated whether a non-adjuvanted vaccine derived from chinese hamster ovary cells was capable of providing protection against woodchuck hepatitis virus (whv). three woodchucks were vaccinated with four 50-microg doses and challenged with a previously characterized virus isolate (whv197). in all three animals, titre levels of antibodies against hepatitis b surface antigens (anti-hbs) exceeded 10 miu/ml, peaking at 150 miu/ml. challenge resulted in productive acute infection in the two non-va ...200515882525
comparative pharmacokinetics of racivir, (+/-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine in rats, rabbits, dogs, monkeys and hiv-infected humans.racivir is a 50:50 racemic mixture of the (-)- and (+)-beta-enantiomers of 2'-deoxy-3'-thia-5-fluorocytosine (ftc), which is being developed for the treatment of hiv and hepatitis b virus (hbv). the (+)-enantiomer of ftc is approximately 10-20-fold less potent than (-)-ftc, but it selects for a different hiv mutation in human lymphocytes. plasma concentrations from a group of 54 rats, 12 pregnant rabbits and 60 dogs enrolled in large toxicity studies using a wide variety of oral doses, were comp ...200515889534
study of the early steps of the hepatitis b virus life cycle.hepatitis b virus (hbv) is a human pathogen, causing the serious liver disease. despite considerable advances in the understanding of the natural history of hbv disease, most of the early steps in the virus life cycle remain unclear. virus attachment to permissive cells, fusion and penetration through cell membranes and subsequent genome release, are largely a mystery. current knowledge on the early steps of hbv life cycle has mostly come from molecular cloning, expression of individual genes an ...200415912187
flow cytometric quantification of t cell proliferation and division kinetics in woodchuck model of hepatitis b.woodchucks infected with woodchuck hepatitis virus (whv) represent the closest natural animal model to study the immunopathogenesis of liver injury caused by essentially noncytopathic, highly human specific hepatitis b virus (hbv). the importance of antiviral t cell response in induction of hepatitis and in control of hbv replication has been demonstrated. however, the understanding of how these responses contribute to the development of different immunomorphological forms of liver disease and t ...200515921160
sequence analysis of the mhc class ii dpb1 gene in chimpanzees (pan troglodytes).the diversity of the mhc class ii region in non-human primates is a focus of biomedical research because this region plays a crucial role in the recognition of antigens in the immune system. in particular, the chimpanzee [pan troglodytes (patr)], which belongs to the superfamily hominoidea, has been used as a human model for the study of diseases such as human hepatitis c virus (hcv), human hepatitis b virus (hbv) and human immunodeficiency virus (hiv) infections, to which only humans and chimpa ...200515932624
pharmacology and pharmacokinetics of the antiviral agent beta-d-2',3'-dideoxy-3'-oxa-5-fluorocytidine in cells and rhesus monkeys.beta-d-2',3'-dideoxy-3'-oxa-5-fluorocytidine (d-fdoc) is an effective inhibitor of human immunodeficiency virus 1 (hiv-1) and hiv-2, simian immunodeficiency virus, and hepatitis b virus (hbv) in vitro. the purpose of this study was to evaluate the intracellular metabolism of d-fdoc in human hepatoma (hepg2), human t-cell lymphoma (cem), and primary human peripheral blood mononuclear (pbm) cells by using tritiated compound. by 24 h, the levels of d-fdoc-triphosphate (d-fdoc-tp) were 2.8 +/- 0.4, ...200515980324
antiviral effect of oral administration of tenofovir disoproxil fumarate in woodchucks with chronic woodchuck hepatitis virus infection.tenofovir disoproxil fumarate (tdf) is a nucleotide analogue approved for treatment of human immunodeficiency virus (hiv) infection. tdf also has been shown in vitro to inhibit replication of wild-type hepatitis b virus (hbv) and lamivudine-resistant hbv mutants and to inhibit lamivudine-resistant hbv in patients and hbv in patients coinfected with the hiv. data on the in vivo efficacy of tdf against wild-type virus in non-hiv-coinfected or lamivudine-naïve chronic hbv-infected patients are lack ...200515980342
effect of adjuvant on reactogenicity and long-term immunogenicity of the malaria vaccine icc-1132 in macaques.icc-1132 is a malaria vaccine candidate based on a modified hepatitis b virus core particle (hbc) bearing putative protective epitopes from the circumsporozoite protein (cs) of plasmodium falciparum. while the epitope carrier itself is immunogenic, its potency can be increased by formulation with adjuvants. as a prelude to phase i clinical trials, rhesus macaques were immunised twice with gmp grade icc--1132 in saline or formulated with the adjuvants alhydrogel (alhydrogel) or montanide((r)) isa ...200515998554
a taqman pcr assay using degenerate primers for the quantitative detection of woodchuck hepatitis virus dna of multiple genotypes.woodchuck hepatitis virus (whv) is a valuable animal model system for studies of hepatitis b virus infection and accurate assessments of whv viral load are necessary in these studies. wild-captured woodchucks that are naturally infected with whv are sometimes used in these studies, however, the sequence variation in whv isolates generally precludes the use of taqman pcr. to facilitate this, we have created a real-time taqman pcr assay for whv using degenerate primers with inosine residues employ ...200516005181
validation of an enzyme-linked immunosorbent assay kit using herpesvirus papio 2 (hvp2) antigen for detection of herpesvirus simiae (b virus) infection in rhesus monkeys.serologic testing for antibody to monkey b virus (bv) in macaque sera is problematic due to the biohazardous nature of bv antigens. herpesvirus papio 2 (hvp2), a herpesvirus of baboons, is nonpathogenic to humans and is genetically and antigenically more closely related to bv than is human herpes simplex virus 1. this paper describes the results of our in-house laboratory that compared a bv antigen-based enzyme-linked immunosorbent assay (elisa) by commercial testing laboratory and an hvp2-based ...200516089172
use of low-dose chlorpromazine in conjunction with environmental enrichment to eliminate self-injurious behavior in a rhesus macaque (macaca mulatta).a 7-year-old, captive-bred, female rhesus macaque was placed in a quarantine facility upon arrival at our institution. at release from quarantine, she was observed pawing at and chewing on her left cheek. physical examination revealed ulcerative lesions on the buccal surface of the left cheek. initial differential diagnoses included cercopithecine herpesvirus 1 (b virus)-induced lesions and bacterial infection. dental abnormalities and cheek pouch foreign body were ruled out during the physical ...200516089178
telbivudine: an upcoming agent for chronic hepatitis b.telbivudine, the prototype member of beta-l-2 -deoxynucleosides, has proven to be safe in in vitro animal and human studies. telbivudine given for 4 weeks resulted in an 8-log reduction of woodchuck hepatitis virus dna, and a 3.8-log reduction of hepatitis b virus dna in human. after 52 weeks of telbivudine treatment there was an approximate 6-log reduction of hepatitis b virus dna levels, hepatitis b virus dna became undetectable by pcr assay in 61% of patients. its antiviral efficacy is signif ...200516107194
clevudine for the treatment of chronic hepatitis b virus infection.chronic hepatitis b virus (hbv) infection is a major health problem that is responsible for < or = 1 million deaths and 500,000 cases of hepatocellular carcinoma worldwide each year. drugs that are currently approved by the fda for the treatment of chronic hbv consist of two groups: the immunomodulators, such as conventional ifn-alpha and pegylated ifn-alpha2a; and nucleoside/nucleotide analogues, such as lamivudine, adefovir dipivoxil and entecavir. however, due to the limitations of these agen ...200516185170
clevudine inhibits hepatitis delta virus viremia: a pilot study of chronically infected woodchucks.in a small controlled study, clevudine, a potent inhibitor of hepadnaviruses, including hepatitis b virus and woodchuck hepatitis virus, suppressed hepatitis delta virus (hdv) viremia in chronically infected woodchucks. suppression was correlated with the marked reduction of woodchuck hepatitis virus surface antigen in individual animals, consistent with the concept that repression of surface antigen expression may be a useful antiviral strategy for hdv.200516189132
comparative antigenicity and immunogenicity of hepadnavirus core proteins.the hepatitis b virus core protein (hbcag) is a uniquely immunogenic particulate antigen and as such has been used as a vaccine carrier platform. the use of other hepadnavirus core proteins as vaccine carriers has not been explored. to determine whether the rodent hepadnavirus core proteins derived from the woodchuck (whcag), ground squirrel (gscag), and arctic squirrel (ascag) viruses possess immunogen characteristics similar to those of hbcag, comparative antigenicity and immunogenicity studie ...200516227284
experimental infection of baboons (papio cynocephalus anubis) with apathogenic and neurovirulent subtypes of herpesvirus papio 2.cercopithecine herpesvirus 16 (herpesvirus papio 2; hvp2) is an alpha-herpesvirus of baboons (papio spp.) that generally causes minimal to inapparent disease in the natural host species. hvp2 is very closely related genetically and antigenically to cercopithecine herpesvirus 1 (monkey b virus; bv) of macaques, which is well known for its extreme lethality in nonmacaque species including humans. preliminary evidence suggests that a mouse model of hvp2 would be an excellent tool for studying zoono ...200516270898
ion-exchange chromatography of hepatitis b virus surface antigen from a recombinant chinese hamster ovary cell line.about 10% of the chinese population are chronic carriers of hepatitis b virus (hbv). thus, the development of a highly efficient process for the preparation of a vaccine based on a recombinant hepatitis b surface antigen (hbsag) is very important to the chinese national immunization program. to this end, the ion exchange chromatography recovery of cho-hbsag from a recombinant chinese hamster ovary cell line was shown to increase from about 55 to 80% by the addition of 1% poly(ethylene glycol) (p ...200516275291
hepatitis b virus cccdna clearance: killing for curing?chronic hepadnavirus infections cause liver damage with ongoing death and regeneration of hepatocytes. in the present study, we set out to quantify the extent of liver turnover by measuring the clonal proliferation of hepatocytes by using integrated viral dna as a genetic marker for individual hepatocyte lineages. liver tissue from woodchucks with chronic woodchuck hepatitis virus (whv) infection was assayed for randomly integrated viral dna by using inverse pcr. serial endpoint dilution of vira ...200516317676
prevalence of enzootic simian viruses among urban performance monkeys in indonesia.animal reservoirs are the most important sources of emerging infectious diseases that threaten human populations. global travel and tourism bring ever-increasing numbers of humans into contact with animals, increasing the likelihood of cross species transmission of infectious agents. non-human primates come into contact with humans in a variety of contexts and may harbor infectious agents with zoonotic potential. we investigated the prevalence of infection with enzootic simian viruses among 20 u ...200516359412
molecular characterization of woodchuck interleukin 15 (wil-15) and detection of its expression in liver samples of woodchucks infected with woodchuck hepatitis virus (whv).interleukin 15 (il-15) is a member of the four-helix bundle cytokine family and has t cell growth factor activity. il-15 plays a unique role in both innate and adaptive immune cell homeostasis, particularly for the development of nk cells and cd8+memory cells. it may be useful for stimulation of specific immune responses in chronic viral infection such as hepatitis b virus infection. the woodchuck model is an informative animal model for studies on hepadnavirus infection and therapeutic interven ...200616406557
altered proteolysis and global gene expression in hepatitis b virus x transgenic mouse liver.hepatitis b virus x (hbx) is essential for the productive infection of hepatitis b virus (hbv) in vivo and has a pleiotropic effect on host cells. we have previously demonstrated that the proteasome complex is a cellular target of hbx, that hbx alters the proteolytic activity of proteasome in vitro, and that inhibition of proteasome leads to enhanced viral replication, suggesting that hbx and proteasome interaction plays a crucial role in the life cycle and pathogenesis of hbv. in the present st ...200616415018
identification of hepatitis b virus genome in faecal sample from wild living chimpanzee (pan troglodytes troglodytes) in gabon.non-invasive faecal sampling in the equatorial forest in gabon allowed the first identification of the hepatitis b virus (hbv-ch(rc170)) genome in samples collected from wild chimpanzees (pan troglodytes troglodytes). the hbv-ch(rcl70)sequence clustered with 100% bootstrap support with previous viral sequences obtained from pan troglodytes subspecies. this is the first evidence of hbv infection in wild apes and confirms that the hbv-like strains thus far characterized in captive apes are directl ...200516461230
[polyethylene glycol-accompanied ion-exchange chromatography to purify recombinant hepatitis b virus surface antigen].the dissociation of virus-like particles of hepatitis b surface antigen (hbsag) during the adsorption-desorption on the solid-phase of chromatography is a main challenge for its purification. herein, poly (ethylene glycol) (peg) was applied as an additive during the purification of hbsag from recombinant chinese hamster ovary (cho) cell culture to improve the hbsag recovery and protect its structural assembly. the presence of 1% of peg10000 in the mobile phase of ion-exchange chromatography (iec ...200516468351
a conserved linear b-cell epitope at the n-terminal region of woodchuck hepatitis virus core protein (whcag).woodchuck hepatitis virus (whv) is a member of family hepadnaviridae and closely related to hepatitis b virus (hbv). the whv core protein (whcag) is a strongly immunogenic protein and forms virus-like particles. whcag may represent a suitable carrier system for b- and t-cell epitopes. however, the lack of a high expression system for whcag and defined antibodies to detect whcag prevents the use of this carrier system. in the present study, vectors expressing whcag with carboxyl-terminal truncati ...200616513185
attachment sites and neutralising epitopes of hepatitis b virus.hepatitis b virus (hbv), the prototype of the family hepadnaviridae is an organ and species-specific human pathogen. although our knowledge about the molecular biology of this highly liver-specific virus has increased, the mechanism of attachment and entry into its host cell, the differentiated hepatocytes is still enigmatic. numerous potential cellular binding sites for the 3 hbv-surface proteins have been described in the past, but none of them have been proven to be a functional receptor. the ...200616554703
characterization of bioactive recombinant woodchuck interleukin-2 amplified by rlm-race and produced in eukaryotic expression system.woodchucks (marmota monax) infected with woodchuck hepatitis virus (whv) represent a highly valuable laboratory model of hepatitis b virus (hbv) infection, in which molecular, immunological and pathological events occurring in infected humans are adequately reflected. to advance studies on t cell immune responses and propagation of hepadnavirus in t lymphocytes in this animal model, we determined the complete sequence of woodchuck interleukin-2 (wil-2) cdna by utilizing rna ligase-mediated rapid ...200616631932
identification of novel chimpanzee mhc class i and ii alleles using an improved sequence-based typing strategy.the chimpanzee (pan troglodytes) is a valuable model for the study of infection with hepatitis c virus and hepatitis b virus, to which only humans and chimpanzees are susceptible. because the cellular immune response plays a crucial role in host defense against these viruses, the analysis of major histocompatibility complex (mhc) (patr) class i and ii allele diversity in chimpanzees is essential for immune response analysis and vaccine development. in the present study, we report a novel, rapid, ...200616698427
lipid-mediated introduction of hepatitis b virus capsids into nonsusceptible cells allows highly efficient replication and facilitates the study of early infection events.the hepatitis b virus (hbv) is an enveloped dna virus which is highly infectious in vivo. in vitro, only primary hepatocytes of humans and tupaia belangeri or the novel heparg cell line are susceptible to hbv, but infection is inefficient and study of early infection events in single cells is unsatisfactory. since hepatoma cells replicate the virus efficiently after transfection, this limited infection efficiency must be related to the initial entry phase. here, we describe the lipid-based deliv ...200616699026
temple monkeys and health implications of commensalism, kathmandu, nepal.the threat of zoonotic transmission of infectious agents at monkey temples highlights the necessity of investigating the prevalence of enzootic infectious agents in these primate populations. biological samples were collected from 39 rhesus macaques at the swoyambhu temple and tested by enzyme-linked immunosorbent assay, western blot, polymerase chain reaction, or combination of these tests for evidence of infection with rhesus cytomegalovirus (rhcmv), cercopithecine herpesvirus 1 (chv-1), simia ...200616707044
genetic recombination for antigenic markers of antigenically different strains of influenza b virus.incorporation of trypsin in agar overlay or fluid maintenance media resulted in enhancement of plaquing efficiency and replication of influenza b viruses in primary chicken embryo fibroblasts. using this improved technique, recombination was attempted with two serologically distinct strains of influenza b virus, b/lee/40 and b/massachusetts/1/71. after mixed infection, two virus clones were selected and characterized in detail. hemagglutination inhibition and neuraminidase inhibition tests showe ...197416789141
primer extension enrichment reaction (peer): a new subtraction method for identification of genetic differences between biological specimens.we developed a conceptually new subtraction strategy for the detection and isolation of target dna and/or rna from complex nucleic acid mixtures, called primer extension enrichment reaction (peer). peer uses adapters and class iis restriction enzymes to generate tagged oligonucleotides from dsdna fragments derived from specimens containing an unknown target ('tester'). subtraction is achieved by selectively disabling these oligonucleotides by extension reaction using ddntps and a double stranded ...200616790564
detailed characterization of the peptide binding specificity of five common patr class i mhc molecules.the chimpanzee (pan troglodytes) is an important model for studying the immune response to several human pathogens, but the study of correlates of immunity has been hindered by the fact that little is known about the epitope-binding specificity of chimpanzee (patr) class i mhc. in the present study we have characterized the peptide binding specificity of several common patr class i molecules. using single amino acid substitution analogs and large peptide libraries, quantitative peptide binding m ...200616791621
rapid identification of small interfering rna that can effectively inhibit the replication of multiple influenza b virus strains.influenza b virus is a cause of substantial morbidity and mortality in humans and current vaccination strategies and antiviral drugs only provide limited protection. here, we report the evaluation of small interfering rna (sirna) for repression of viral replication in cultured cells as well as in chicken embryos. several sirnas targeting conserved regions of the virus (in chemically synthesized or plasmid-encoded forms) were found to effectively block the replication of the influenza b virus. th ...200616856616
immunology of hdv infection.hepatitis delta virus (hdv) infection may occur as coinfection with hepatitis b virus (hbv) or as superinfection of a chronically hbv-infected patient. a strong antibody response is mounted, which persists for many years; however, it is not able to modulate the course of infection. in most cases the superinfection takes a chronic course. in patients with inactive disease (hdv pcr negative) an oligospecific t-helper cell immune response and a cytotoxic t-cell response were found, which were absen ...200616903227
clevudine: a potent inhibitor of hepatitis b virus in vitro and in vivo.clevudine (clv) is a nucleoside analog of the unnatural l-configuration that has potent anti-hepatitis b virus (hbv) activity in vitro and in vivo with a favorable toxicity profile in all species tested. in cell culture, clv is readily phosphorylated to the corresponding 5'-triphosphate form of the compound. the mechanism of action of clv involves the inhibition of the hbv polymerase by clv 5'-triphosphate. in vivo efficacy studies performed in the duck and woodchuck models showed marked, rapid ...200617009935
[inhibition of hepatitis b and duck hepatitis b virus replication by apobec3g].to investigate the effect of apolipoprotein b mrna-editing enzyme catalytic polypeptide-like 3g (apobec3g) mediated antiviral activity against hepatitis b virus (hbv) and duck hepatitis b virus (dhbv).200617064466
bicistronic woodchuck hepatitis virus core and gamma interferon dna vaccine can protect from hepatitis but does not elicit sterilizing antiviral immunity.the immunity elicited against nucleocapsid of hepatitis b virus (hbv) and closely related woodchuck hepatitis virus (whv) has been shown to be important in resolution of hepatitis and protection from infection. further, activity of gamma interferon (ifn-gamma), which may directly inhibit hepadnavirus replication, promotes antiviral defense and favors t helper cell type 1 (th1) response, which is seemingly a prerequisite of hbv clearance. in this study, to enhance induction of protective immunity ...200717079319
is the anti-sarcoma and anti-viral cytokine "plasma factor" a novel chicken y-box protein?a line of research beginning in the early 1960s with the observation that west nile virus and, later, several strains of rabies virus could inhibit the development of the rous sarcoma virus-induced tumor in the wing-web of chicken (a "sarcoma-blockade") eventually culminated in the characterization of a 14-kda circulating anti-sarcoma and anti-viral activity christened "plasma factor" (pf) which, unlike the interferons, inhibited the replication of diverse rna-containing viruses, but not of any ...200617131907
viral and cellular determinants involved in hepadnaviral entry.hepadnaviridae is a family of hepatotropic dna viruses that is divided into the genera orthohepadnavirus of mammals and avihepadnavirus of birds. all members of this family can cause acute and chronic hepatic infection, which in the case of human hepatitis b virus (hbv) constitutes a major global health problem. although our knowledge about the molecular biology of these highly liver-specific viruses has profoundly increased in the last two decades, the mechanisms of attachment and productive en ...200717206752
the woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis b virus infection.this review describes the woodchuck and the woodchuck hepatitis virus (whv) as an animal model for pathogenesis and therapy of chronic hepatitis b virus (hbv) infection and disease in humans. the establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined whv inocula, have enhanced our understanding of the virology and immunology of hbv infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. ...200717206759
differential distribution of antibodies to different viruses in young animals in the free-ranging rhesus macaques of cayo santiago.the breeding colony of free-ranging rhesus macaques was established in 1938 in cayo santiago (cs) with animals collected in northern india. the seroprevalence to cercopithecine herpesvirus type 1 (b virus) and simian retroviruses has been studied previously.200617214665
a randomized placebo-controlled, dose-finding study of oral lb80380 in hbeag-positive patients with chronic hepatitis b.lb80380 is potent antiviral agent against hepatitis b virus (hbv) in vitro and in the woodchuck model. it has an excellent preclinical safety profile including lower potential for renal toxicity than adefovir. it is effective against both wild-type and ymdd mutant hbv. lb80380 is converted to its parent drug, lb80331, after oral absorption, and further metabolized to its active form, lb80317.200617302367
hepatitis b virus replication and liver disease progression: the impact of antiviral therapy.chronic hepatitis b virus (hbv) infection is a serious health issue worldwide. the presence of hbv replication markers--hepatitis b e antigen (hbeag) or hbv dna--is associated with continuing hepatitis activity or intermittent hepatitis flares and subsequent disease progression, including hepatic decompensation and development of liver cirrhosis or hepatocellular carcinoma (hcc). long-term (>10 years) prospective studies in patients >30 years of age have shown that hbeag seropositivity is associ ...200617310811
immunosuppression reactivates viral replication long after resolution of woodchuck hepatitis virus infection.resolution of hepatitis b virus (hbv) infection is characterized by coordinated humoral and cellular immune responses. immunity is durable over decades, protecting the host from reinfection and potential activation of residual hbv. woodchucks infected at birth with woodchuck hepatitis virus (whv) cleared viremia and developed antibodies to surface antigen (anti-whs). woodchucks became seronegative for anti-whs 3-6 years later, but in some, whv dna was detected in serum, liver, and/or peripheral ...200717326155
human monoclonal antibody against hepatitis b virus surface antigen (hbsag).hepatitis b virus (hbv) is one of the main pathogens responsible for hepatitis and hepatocellular carcinoma. human plasma-derived hepatitis b immune globulin (hbig) is being used for prophylactic and liver transplantation currently. however, it may be necessary to replace a hbig with a recombinant one because of limited availability of human plasma with high anti-hbsag antibody titer and possible contamination of human pathogens. a chinese hamster ovary (cho) cell line, hb-c7a, was established w ...200717343928
changes in the titer of anti-b virus antibody in captive macaques (macaca fuscata, m. mulatta, m. fascicularis).changes in levels of antibody to b virus (cercopithecine herpesvirus 1; bv) were examined in bv-positive macaques by elisa. we observed increases in anti-bv igg titers in a bv-infected cynomolgus monkey after overseas transportation by air and in a rhesus monkey after transfer from an outdoor group cage to an indoor individual cage. although shedding of infectious virus was not examined, the increase in antibody titer suggested reactivation of bv. interestingly, we also found an increase in anti ...200717348300
entry of duck hepatitis b virus into primary duck liver and kidney cells after discovery of a fusogenic region within the large surface protein.hepatitis b viruses exhibit a narrow host range specificity that is believed to be mediated by a domain of the large surface protein, designated l. for duck hepatitis b virus, it has been shown that the pre-s domain of l binds to carboxypeptidase d, a cellular receptor present in many species on a wide variety of cell types. nonetheless, only hepatocytes become infected. it has remained vague which viral features determine host range specificity and organotropicity. by using chymotrypsin to trea ...200717360753
woodchuck dendritic cells generated from peripheral blood mononuclear cells and transduced with recombinant human adenovirus serotype 5 induce antigen-specific cellular immune responses.woodchucks infected with the woodchuck hepatitis virus (whv) is the best available animal model for testing the immunotherapeutic effects of dendritic cells (dcs) in the setting of a chronic infection, as woodchucks develop a persistent infection resembling that seen in humans infected with the hepatitis b virus. in the present study, dcs were generated from woodchuck peripheral blood mononuclear cells (wdcs) in the presence of human granulocyte macrophage colony-stimulating factor (hgm-csf) and ...200717385694
chimeric adenovirus 5/35 vector containing the clade c hiv gag gene induces a cross-reactive immune response against hiv.most of the recent hiv studies have focused on the clade b virus subtype. however, it is estimated that half the hiv patients in developing countries are infected with virus belonging to clade c. therefore, a vaccine against hiv clade c is urgently required. in this study, we evaluate the immunogenicity and protective immunity of an adenovirus vector (ad) in balb/c mice and cynomolgus monkeys. we developed an hiv vaccine containing the hiv clade c gag gene using a replication-defective chimeric ...200717386962
tumor necrosis factor activates a conserved innate antiviral response to hepatitis b virus that destabilizes nucleocapsids and reduces nuclear viral dna.tumor necrosis factor (tnf) is critical for the control of hepatitis b virus (hbv) in the clinical setting and in model systems. tnf induces noncytopathic suppression and clearance of hbv in animal models, possibly through reduction of viral nucleocapsids, but the mechanism is not well described. here, we demonstrate the molecular mechanism and broad host range for tnf action against hbv. we show that tnf rapidly blocks hbv replication by promoting destabilization of preexisting cytoplasmic vira ...200717475655
evidence-based strategies to improve immunization compliance of postgraduate medical trainees at large academic-medical facilities.the purpose of this evaluation is to assess the effectiveness of the modifications made by the university of toronto postgraduate medical education to improve medical trainee compliance with the immunization standards set forth in national guidelines, provincial regulations and protocols and university policy. trainee compliance with immunization requirements were evaluated as of january 2003, 2004 and 2005. statistically significant increases in compliance rates for all required immunizations-- ...200717491572
immunomodulation as an option for the treatment of chronic hepatitis b virus infection: preclinical studies in the woodchuck model.new therapeutic approaches for chronic hepatitis b virus infection based on immunomodulation are now under investigation. the woodchuck model for hepatitis b virus infection has emerged as a useful animal model for the evaluation of such approaches, after developing necessary assays and reagents for immunologic studies in this model. conventional and novel vaccines such as dna vaccines were tested in woodchucks for their ability to induce protective immune responses against challenge infection w ...200717501692
rapid emergence of a viral resistant mutant in whv chronically infected woodchucks treated with lamivudine and a pre-s/s cho-derived hepatitis b virus vaccine.to determine whether the addition of a pre-s/s human vaccine increases the antiviral activity of lamivudine, four woodchucks were treated with a daily dose of 100 mg/kg lamivudine and four 50 microg doses of cho-derived pre-s/s human vaccine. whv dna titres decreased up to two logarithms in three woodchucks. at week 4, in three of the animals, the sequence analysis showed a predominant strain containing a nucleotide change from a to t at position 1696 of domain b of the whv dna polymerase. vacci ...200717531355
evidence for virus closely related to avian myeloblastosis-associated virus type 1 in a commercial stock of chickens.a two-round nested polymerase chain reaction assay detected rous associated virus-1 (rav-1), a prototype laboratory strain of avian leukosis virus of subgroup a (alv-a). surprisingly, the test failed to detect three field isolates of alv-a but did detect virus in one commercial stock of chickens (stock f). the sequence analysis of a core of 290 nucleotides of the env gene gave evidence that the virus from stock f was closely related to avian myeloblastosis-associated virus type one (mav-1). othe ...200317585462
antiviral effect of orally administered (-)-beta-d-2-aminopurine dioxolane in woodchucks with chronic woodchuck hepatitis virus infection.(-)-beta-d-2-aminopurine dioxolane (apd) is a nucleoside prodrug that is efficiently converted to 9-(beta-d-1,3-dioxolan-4-yl)guanine (dxg). dxg has antiviral activity in vitro against hepatitis b virus (hbv) but limited aqueous solubility, making it difficult to administer orally to hbv-infected individuals. apd is more water soluble than dxg and represents a promising prodrug for the delivery of dxg. a placebo-controlled, dose-ranging efficacy and pharmacokinetic study was conducted with woodc ...200717606676
a vectored measles virus induces hepatitis b surface antigen antibodies while protecting macaques against measles virus challenge.hepatitis b virus (hbv) acute and chronic infections remain a major worldwide health problem. towards developing an anti-hbv vaccine with single-dose scheme potential, we engineered infectious measles virus (mv) genomic cdnas with a vaccine strain background and expression vector properties. hepatitis b surface antigen (hbsag) expression cassettes were inserted into this cdna and three mvs expressing hbsag at different levels generated. all vectored mvs, which secrete hbsag as subviral particles ...200717634218
serological evidence of hepatitis e virus infection in an indigenous north american population.hepatitis e virus (hev) infections are thought to be uncommon in north america. recently, hev transmission has been reported following the consumption of deer meat. because deer are closely related to caribou and caribou meat is a staple of the canadian inuit and the american eskimo diet, the present study explored the seroprevalence of hev infection in an isolated canadian inuit community.200717637946
chemoimmunotherapy of chronic hepatitis b virus infection in the woodchuck model overcomes immunologic tolerance and restores t-cell responses to pre-s and s regions of the viral envelope protein.treatment of chronic hepatitis b virus (hbv) infection could combine potent antiviral drugs and therapeutic vaccines to overcome immunological tolerance and induce the recovery phenotype to protect against disease progression. conventional vaccination of woodchucks chronically infected with the woodchuck hepatitis virus (whv) elicited differential t-cell response profiles depending on whether or not carriers were treated with the potent antiviral drug clevudine (clv), which significantly reduces ...200717652398
[common linear b-cell epitopes in human hepatitis b virus core protein and woodchuck hepatitis virus core protein].to search for and verify some common b cell epitopes in the core proteins of woodchuck hepatitis virus and human hepatitis b virus.200717711632
candidate genes responsible for human hepatocellular carcinoma identified from differentially expressed genes in hepatocarcinogenesis of the tree shrew (tupaia belangeri chinesis).aim: to explore gene expression profiles during hepatocarcinogenesis of the tree shrew, and to find the genes responsible for human hepatocellular carcinoma (hcc). methods: tree shrews were used as an animal model for hcc induction employing aflatoxin b(1) (afb(1)) alone or afb(1) plus hepatitis b virus (hbv) as etiological factors. gene expression profiles from the tissues of hcc, hcc-surrounding liver tissues (para-hcc) and the corresponding biopsies taken from the same animals before hcc had ...200817714471
complete-genome analysis of hepatitis b virus from wild-born chimpanzees in central africa demonstrates a strain-specific geographical cluster.in order to determine whether geographical or species clustering accounts for the distribution of hepatitis b virus (hbv) in subspecies of chimpanzees in africa, four complete chimpanzee hbv (chhbv) genome sequences were obtained from eight hepatitis b surface antigen-positive wild-born chimpanzees from cameroon, republic of congo and gabon. the serological profiles of these chimpanzees corresponded to the acute or chronic highly replicative phase of hbv infection, as confirmed by high plasma hb ...200717872519
development of a novel mouse model to evaluate drug candidates against hepatitis b virus.woodchuck hepatitis virus (whv)-infected woodchucks have been used for preclinical development of drugs against hepatitis b virus (hbv). however, there is no simple in vivo model to evaluate small amounts of compounds against hbv. to develop such a model, hepad38 cells, in which hbv replication is regulated by tetracycline (tet), were grown as subcutaneous tumours in nude mice. mice developing viraemia were then left untreated or given tet in the drinking water. in some of the mice given tet, it ...200717907379
the interferon-alpha gene family of marmota himalayana, a chinese marmot species with susceptibility to woodchuck hepatitis virus infection.the interferon-alpha (ifn-alpha) gene family is an important part of the immune system. recombinant interferon-alpha is widely used to treat viral hepatitis and malignant diseases. marmota himalayana has been found to be susceptible to woodchuck hepatitis virus, a virus genetically related to hepatitis b virus (hbv), and is suitable as an animal model for studies on hbv infection. here, the ifn-alpha gene family of m. himalayana (cwifn-alpha) was characterized. sequence data indicate that the cw ...200817936902
therapeutic vaccination in chronic hepatitis b: preclinical studies in the woodchuck model.interferon-alpha and nucleoside analogues are available for the treatment of chronic hepatitis b virus (hbv) infection but do not lead to a satisfactory result. new findings about the immunological control of hbv during acute infection suggest the pivotal role of t-cell mediated immune responses. several preclinical and clinical trials were undertaken to explore the possibility of stimulating specific immune responses in chronically infected animals and patients by vaccination. however, vaccinat ...200717958643
persistent occult hepatitis b virus infection: experimental findings and clinical implications.hepatitis b virus (hbv) is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. in addition to a symptomatic, serologically evident infection, occult persistent hbv carriage has been identified since nucleic acid amplification assays of enhanced sensitivity became introduced for detection of hepadnaviral genomes and their replicative intermediates. current evidence indicates that occult hbv infection is a common and long-term consequence of resolution of a ...200717963292
prevalence of antibody reaction with cercopithecine herpesvirus 1 antigen in macaca cyclopis, macaca fascicularis, and papio anubis in taiwan.a total of 284 non-human primate sera were collected between december 2004 and september 2005 and tested by a commercially available dot immunobinding assay for the antibodies to cercopithecine herpesvirus 1, an alphaherpesvirus with high mortality for infected humans.200717976038
natural iminosugar derivatives of 1-deoxynojirimycin inhibit glycosylation of hepatitis viral envelope proteins.a silkworm (bombyx mori l.) extract known to contain naturally occurring iminosugars, including 1-deoxynojirimycin (1-dnj) derived from the mulberry tree (morus alba l.), was evaluated in surrogate hcv and hbv in vitro assays. antiviral activity of the silkworm extract and one of its purified constituents, 1-dnj, was demonstrated against bovine viral diarrhea virus (bvdv) and gb virus-b (gbv-b), both members of the flaviviridae family, and against woodchuck hepatitis virus (whv) and hepatitis b ...200717978803
the role of the woodchuck model in the treatment of hepatitis b virus infection.experimental studies of animals with chronic hepadnavirus infection could provide valuable insight into optimal therapeutic strategies for individuals with chronic hbv infection. in this review, we focus on the contributions of the woodchuck model to our understanding of hbv biology and on its role in the development of antiviral drug. furthermore, we consider the implications of studies focusing on the natural history of whv infection for the management of hbv and the capacity of treatment to p ...200717981226
discrimination of antibody to herpes b virus from antibody to herpes simplex virus types 1 and 2 in human and macaque sera.the antigenic cross-reactive characteristics of herpes b virus and herpes simplex virus (hsv) type 1 (hsv-1) and hsv-2 are responsible for false-positive diagnoses by serological assays in humans and macaques. in the present study, we developed a fluorometric indirect enzyme-linked immunosorbent assay (elisa) with recombinant herpes b virus glycoprotein d (gd) and hsv-1 and hsv-2 gg (gg-1 and gg-2, respectively) to discriminate between the three primate herpesvirus infections. the secreted form ...200817989200
vaccination of chicks with live attenuated subtype b avian metapneumovirus vaccines: protection against challenge and immune responses can be unrelated to vaccine dose.live attenuated subtype b avian metapneumovirus (ampv) vaccines from two different commercial sources (vac 1 and vac 2) were used to vaccinate two groups of day-old specific-pathogen-free chicks. the chicks were challenged at 21 or 49 days of age with a virulent subtype b virus. parameters compared were persistence of vaccine viruses, their ability to induce humoral antibody responses, and the protection they offered against virulent challenge. vac 1 virus was detectable for at least 14 days aft ...200717992934
limited use of centritech lab ii centrifuge in perfusion culture of rcho cells for the production of recombinant antibody.perfusion cultures of recombinant chinese hamster ovary cells, producing recombinant antibody against the s surface antigen of hepatitis b virus, were carried out in continuous and intermittent mode using a centritech lab ii centrifuge. in the continuous perfusion process, despite the absence of shear stress from the pump head, long-term operation was not possible because of continuously repeated exposure to oxygen limitation and low temperature, as well as shear stress from centrifugal force. i ...200818092799
combination of an antiviral drug and immunomodulation against hepadnaviral infection in the woodchuck model.the essential role of multispecific immune responses for the control of hepatitis b virus (hbv) infection implies the need of multimodal therapeutic strategies for chronic hbv infection, including antiviral chemotherapy and immunomodulation. this hypothesis was tested in the woodchuck model by a combination of lamivudine pretreatment and subsequent immunizations of woodchucks chronically infected with woodchuck hepatitis virus. the immunizations were performed with dna vaccines or antigen-antibo ...200818160442
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