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efficacy of single intravenous injection of peramivir against influenza b virus infection in ferrets and cynomolgus macaques.we evaluated the efficacy of single intravenous dose peramivir for treatment of influenza b virus infection in ferrets and cynomolgus macaques in the present study. a single dose of peramivir (30 and 60 mg/kg) given to ferrets on 1 day post-infection with influenza b virus significantly reduced virus titers in nasal washes and total virus shedding as measured by areas under the curve (auc) by 2 log(10) compared with control group. furthermore, nasal virus titers on day 2 post infection and aucs ...201121844317
HBV mutants associated with HBsAg loss: Chicken or egg? 201121969004
Development of an animal model for radiofrequency ablation of primary, virally induced hepatocellular carcinoma in the woodchuck.To develop a consistent and reproducible method in an animal model for studies of radiofrequency (RF) ablation of primary hepatocellular carcinoma (HCC).201121959057
Soluble rhesus lymphocryptovirus gp350 protects against infection and reduces viral loads in animals that become infected with virus after challenge.Epstein-Barr virus (EBV) is a human lymphocryptovirus that is associated with several malignancies. Elevated EBV DNA in the blood is observed in transplant recipients prior to, and at the time of post-transplant lymphoproliferative disease; thus, a vaccine that either prevents EBV infection or lowers the viral load might reduce certain EBV malignancies. Two major approaches have been suggested for an EBV vaccine- immunization with either EBV glycoprotein 350 (gp350) or EBV latency proteins (e.g. ...201122028652
Nanobodies®: new ammunition to battle viruses.In 1989, a new type of antibody was identified, first in the sera of dromedaries and later also in all other species of the Camelidae family. These antibodies do not contain a light chain and also lack the first constant heavy domain. Today it is still unclear what the evolutionary advantage of such heavy chain-only antibodies could be. In sharp contrast, the broad applicability of the isolated variable antigen-binding domains (VHH) was rapidly recognized, especially for the development of thera ...201121939690
seroprevalence of bv (macacine herpesvirus 1) in bred cynomolgus monkeys in cambodia.the seroprevalence of b virus (bv, macacine herpesvirus 1) in bred cynomolgus monkeys (macaca fascicularis) in cambodia was investigated. blood samples were collected by venous puncture between 2007 and 2011, and a commercially available enzyme-linked immunosorbent assay (elisa) kit was used to detect igg antibodies against bv. a total of 1710 blood samples were examined, and the overall prevalence of bv antibodies was 33.92% (580/1,710). the young adult (2-6 years) monkeys had a seroprevalence ...201121997241
Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication.Kumar M, Bandi S, Cheng K, Gupta S. Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication. Xenotransplantation 2011; 18: 380-389. © 2011 John Wiley & Sons A/S. Abstract: Background: Studies of natural hepatitis B virus infection must be restricted to humans or primates due to viral species-specificity. Alternative hepadnavirus animal models, e.g., woodchuck hepatitis virus in captive woodchucks, are not convenient, whi ...201122168144
evaluating functional antibodies in rhesus monkeys immunized with hepatitis b virus surface antigen vaccine with novel adjuvant formulations.effective and safe novel adjuvants are of great interest to the vaccine research community. in this study, we describe our evaluation of adjuvant formulations containing a tlr9 agonist adjuvant (iss1018) or iscomatrix™ adjuvant for a two-dose regimen of hepatitis b virus surface antigen virus-like particle vaccine in mice and rhesus macaques. our results show a 10-20 fold improvement in ab binding titers determined in an antigen-sandwich assay for adjuvant formulations with iscomatrix™ adjuvant, ...201122001120
the expression of pd-1 ligands and their involvement in regulation of t cell functions in acute and chronic woodchuck hepatitis virus infection.the programmed cell death 1 (pd-1)/programmed death-1 ligand 1 (pd-l1) system may play a role in the negative regulation of t cell functions in hepatitis b virus (hbv) infection. thus, it is important to study its role in the widely used animal model for hbv infection of woodchucks with woodchuck hepatitis virus (whv).201122022563
Molecular characterisation of an avihepadnavirus isolated from Psittacula krameri (ring-necked parrot).Avihepadnaviruses have been documented previously in ducks, herons, geese, storks and cranes. Here, we describe the full genome of a new avihepadnavirus isolated from Psittacula krameri (ring-necked parrot) in Poland. The parrot hepatitis B virus (PHBV) genome (3042 bp) shares <76% sequence identity with other avihepadnavirus isolates and is phylogenetically most closely related to heron and stork hepatitis B viruses isolates. PHBV has a genome organization similar to that of other hepadnaviruse ...201122183110
evaluation of mitochondrial toxicity in marmota himalayana treated with metacavir, a novel 2',3'-dideoxyguanosine prodrug for treatment of hepatitis b virus.metacavir (pna) is a novel synthetic nucleoside analogue for the treatment of hepatitis b virus (hbv). our recent studies showed that pna, a prodrug of 2',3'-dideoxyguanosine (ddg), exhibited lower mitochondrial toxicity in long-term cultures of hepg2 cells. in the current study, we examined the long-term effects of pna on mitochondrial toxicity in marmota himalayana (himalayan marmot). himalayan marmots were treated daily with oral pna (50 or 100 mg/kg), ziduvidine (azt) (100 mg/kg), or water ( ...201121282436
[sero-epidemiology of six viruses natural infection in tupaia belangeri chinensis].tupaia (tupaia belangeris chinensis, tree shrew) as a new experiment animal in medicine are non-rodent, small animals and close to primates in evolution. experimental animals infected with viruses will affect the animal's health, interference experiment, and even endanger the operator's safety. therefore, the viral infection in experimental animals has long been considered an important part of quality control. lack of clearer viral natural infection information on the t. belangeris limits its us ...201121341379
[progress on establishment of tree shrew (tupaia) chronic infection with hbv in vivo].hepatitis b virus (hbv) infection is one of the important health problems worldwide, especially in china. feasible and effective animal models of hbv infection in vivo are prerequisite for the hbv-related basic and clinical studies. located in the highly prevalent region of hbv and hepatocellular carcinoma (hcc), the laboratory of guangxi cancer institute has focused on the cause, pathogenesis and chemoprevention of hcc, and has started the work of establishing tree shrew (tupaia) models of hbv ...201121341392
six-month repeated dose toxicity of orally administered metacavir in rhesus monkeys.to explore the toxicities of metacavir, a novel deoxyguanosine analog with an anti-hepatitis b virus (hbv) potential, in a 6-month repeated dosing in rhesus monkeys.201120347583
detection of hepatitis b virus in serum and liver of chickens.abstract: hepatitis b virus (hbv) is one of the most important human pathogens. its existence in food animals could present a significant threat to public health. the objective of this study was to determine if hbv is present in serum and liver of chickens. a total of 129 serum samples from broiler chickens were collected for the detection of hbv antigens and antibodies, and 193 liver samples were tested for hbv dna sequence by pcr and for the existence of hbv antigens by immunohistochemistry. t ...201222217003
prokaryotic expression of woodchuck cytotoxic t lymphocyte antigen 4 (wctla-4) and preparation of polyclonal antibody to wctla-4.cytotoxic t lymphocyte antigen 4 (ctla-4) is an inhibitory t cell receptor predominately expressed on activated t cells and plays an important role in regulation of specific t cell responses to viral infection. the woodchuck model is an informative animal model for hepatitis b virus (hbv) infection. in this study, the extracellular region of woodchuck ctla-4 (wctla-4) was cloned and the fusion protein of gst-wctla-4 was expressed and purified. polyclonal antibody against gst-wctla-4 (anti-gst-wc ...201222040606
live attenuated influenza viruses produced in a suspension process with avian age1.cr.pix cells.current influenza vaccines are trivalent or quadrivalent inactivated split or subunit vaccines administered intramuscularly, or live attenuated influenza vaccines (laiv) adapted to replicate at temperatures below body temperature and administered intranasally. both vaccines are considered safe and efficient, but due to differences in specific properties may complement each other to ensure reliable vaccine coverage. by now, licensed laiv are produced in embryonated chicken eggs. in the near futur ...201223110398
influenza a and b virus attachment to respiratory tract in marine mammals.patterns of virus attachment to the respiratory tract of 4 marine mammal species were determined for avian and human influenza viruses. attachment of avian influenza a viruses (h4n5) and (h7n7) and human influenza b viruses to trachea and bronchi of harbor seals is consistent with reported influenza outbreaks in this species.201222516350
transmission of influenza b viruses in the guinea pig.epidemic influenza is typically caused by infection with viruses of the a and b types and can result in substantial morbidity and mortality during a given season. here we demonstrate that influenza b viruses can replicate in the upper respiratory tract of the guinea pig and that viruses of the two main lineages can be transmitted with 100% efficiency between inoculated and naïve animals in both contact and noncontact models. our results also indicate that, like in the case for influenza a virus, ...201222301149
herpes b virus, macacine herpesvirus 1, breaks simplex virus tradition via major histocompatibility complex class i expression in cells from human and macaque hosts.b virus of the family herpesviridae is endemic to rhesus macaques but results in 80% fatality in untreated humans who are zoonotically infected. downregulation of major histocompatibility complex (mhc) class i in order to evade cd8(+) t-cell activation is characteristic of most herpesviruses. here we examined the cell surface presence and total protein expression of mhc class i molecules in b virus-infected human foreskin fibroblast cells and macaque kidney epithelial cells in culture, which are ...201222973043
[epidemiological survey of a captive chinese rhesus macaque breeding colony in yunnan for srv, stlv and bv].nonhuman primates are critical resources for biomedical research. rhesus macaque is a popularly used laboratory nonhuman primate that share many characteristics with humans. however, rhesus macaques are the natural host of two exogenous retroviruses, srv (simian type d retrovirus) and stlv (simian t lymphotropic virus). srv and stlv may introduce potentially significant confounding factors into the study of aids model. moreover, b virus (ceropithecine herpesvirus 1) is likely to harm not only rh ...201222345008
virus-like particles of hepatitis b virus core protein containing five mimotopes of infectious bursal disease virus (ibdv) protect chickens against ibdv.current infectious bursal disease virus (ibdv) vaccines suffer from maternal antibody interference and mimotope vaccines might be an alternative. previously we demonstrated an ibdv vp2 five-mimotope polypeptide, 5epis, elicited protective immunity in chickens. in the current study, the 5epis gene was inserted into a plasmid carrying human hepatitis b virus core protein (hbc) gene at its major immunodominant region site. the recombinant gene was efficiently expressed in escherichia coli to produc ...201222285269
[factors influencing long-term hepatitis b virus infection of the tree shrew (tupaia belangeri chinensis) as an in vivo model of chronic hepatitis b].to determine the methods for establishing an in vivo model of long-term hepatitis b virus (hbv) infection in the chinese tree shrew (tupaia belangeri chinensis).201223207228
molecular biology of the hepatitis b virus for clinicians.hepatitis b virus (hbv) infection is one of the major global health problems, especially in economically under-developed or developing countries. hbv infection can lead to a number of clinical outcomes including chronic infection, cirrhosis and liver cancer. it ranks among the top 10 causes of death, being responsible for around 1 million deaths every year. despite the availability of a highly efficient vaccine and potent antiviral agents, hbv infection still remains a significant clinical probl ...201225755457
[study on antibody response to revaccination of hepatitis b vaccine among firstly low-response adults].to evaluate and compare the antibody to hepatitis b virus (hbv) surface antigen (anti-hbs) response and the influent factors of revaccination of 4 kinds of hepatitis b vaccine (hepb) among firstly low-response adults.201223157885
molecular characterization of woodchuck interleukin-10 receptor and enhanced function of specific t cells from chronically infected woodchucks following its blockade.interleukin 10 (il-10) is a pleiotropic cytokine acting on a variety of immune cells through the cell surface receptor (il-10r). it has been suggested to resuscitate antiviral immunity by interfering with il-10/il-10r pathway. the woodchuck model infected by woodchuck hepatitis virus (whv) represents an informative animal model to study hepatitis b virus (hbv) infection. in this study, the woodchuck il-10r (wil-10r) was molecularly cloned and characterized, showing high similarity of its nucleot ...201222784930
hepatitis b virus x protein stimulates gene expression selectively from extrachromosomal dna templates.chronic hepatitis b virus (hbv) infection is a major risk factor for liver cancer development. hbv encodes the hepatitis b virus x (hbx) protein that promotes transcription of the viral episomal dna genome by the host cell rna polymerase ii. here we provide evidence that hbx accomplishes this task by a conserved and unusual mechanism. thus, hbx strongly stimulates expression of transiently transfected reporter constructs, regardless of the enhancer and promoter sequences. this activity invariabl ...201222744635
dna prime-adenovirus boost immunization induces a vigorous and multifunctional t-cell response against hepadnaviral proteins in the mouse and woodchuck model.induction of hepatitis b virus (hbv)-specific cytotoxic t cells by therapeutic immunization may be a strategy to treat chronic hepatitis b. in the hbv animal model, woodchucks, the application of dna vaccine expressing woodchuck hepatitis virus (whv) core antigen (whcag) in combination with antivirals led to the prolonged control of viral replication. however, it became clear that the use of more potent vaccines is required to overcome whv persistence. therefore, we asked whether stronger and mo ...201222718818
molecular characterization of the type i ifn receptor in two woodchuck species and detection of its expression in liver samples from woodchucks infected with woodchuck hepatitis virus (whv).type i interferons (ifn-α/β) serve as the first line of defense against viral infection and share the same type i ifn receptor (ifnar) complex, which is composed of ifnar1 and -2. the eastern woodchuck (marmota monax) and chinese woodchuck (marmota himalayana) are suitable for studying hepatitis b virus (hbv) infection. here, the complete or partial sequences of the ifnars of both species were obtained and analyzed. small interference rnas targeting wifnar1 and -2 specifically down-regulated the ...201222705153
human hepatitis b virus production in avian cells is characterized by enhanced rna splicing and the presence of capsids containing shortened genomes.experimental studies on hepatitis b virus (hbv) replication are commonly done with human hepatoma cells to reflect the natural species and tissue tropism of the virus. however, hbv can also replicate, upon transfection of virus coding plasmids, in cells of other species. in such cross-species transfection experiments with chicken lmh hepatoma cells, we previously observed the formation of hbv genomes with aberrant electrophoretic mobility, in addition to the those dna species commonly seen in hu ...201222624002
role of toll-like receptor 2 in the immune response against hepadnaviral infection.the toll-like receptor 2 (tlr2) has recently been recognized to play an important role in the pathogenesis of chronic hepatitis b virus (hbv) infection. in the present study, we examined the role of tlr2 in hepadnaviral infection in hepatoma cell lines and the woodchuck model.201222617154
entecavir treatment of chronic hepatitis d.hepatitis d virus (hdv) requires hepatitis b surface antigen (hbsag) to propagate infection and cause disease. entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis b virus (hbv) cccdna and woodchuck surface antigen. the aim of this study was to investigate the efficacy of entecavir in chronic hepatitis d (chd).201222573857
subset of suz12/prc2 target genes is activated during hepatitis b virus replication and liver carcinogenesis associated with hbv x protein.chronic hepatitis b virus (hbv) infection is a major risk factor for developing liver cancer, and the hbv x protein (px) has been implicated as a cofactor in hepatocyte transformation. we have shown that hbv replication as well as in vitro transformation by px are associated with induction of the mitotic polo-like kinase 1 (plk1) and down-regulation of the chromatin remodeling components suz12 and znf198. herein, we demonstrate the same inverse relationship between plk1 and suz12/znf198 in liver ...201222505317
species association of hepatitis b virus (hbv) in non-human apes; evidence for recombination between gorilla and chimpanzee variants.hepatitis b virus (hbv) infections are widely distributed in humans, infecting approximately one third of the world's population. hbv variants have also been detected and genetically characterised from old world apes; gorilla gorilla (gorilla), pan troglodytes (chimpanzee), pongo pygmaeus (orang-utan), nomascus nastusus and hylobates pileatus (gibbons) and from the new world monkey, lagothrix lagotricha (woolly monkey). to investigate species-specificity and potential for cross species transmiss ...201222432021
transcriptomic analysis of the woodchuck model of chronic hepatitis b.the eastern woodchuck (marmota monax) is naturally infected with woodchuck hepatitis virus (whv), a hepadnavirus closely related to the human hepatitis b virus (hbv). the woodchuck is used as an animal model for studying chronic hepatitis b (chb) and hbv-associated hepatocellular carcinoma (hcc) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. to address this major limitation of the model, we report here the sequencing, assembly, and annotation ...201222431061
ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis b virus.overexpression of squamous cell carcinoma antigen 1 (scca1) in hepatitis g2 (hepg2) and chinese hamster ovary cells can increase hepatitis b virus (hbv) binding capacity by interacting with the pres1 domain of the hbv surface antigen. however, the magnitude of increase in binding capacity was higher by several orders in the former, indicating the existence of additional factor(s) produced by hepg2 cells, which facilitates hbv attachment. ferritin light chain (ftl) was identified as the sole high ...201222359459
hepatitis delta virus infects the cells of hepadnavirus-induced hepatocellular carcinoma in woodchucks.hepatitis delta virus (hdv) is a natural subviral agent of human hepatitis b virus (hbv). hdv enhances liver damage during concomitant infection with hbv. the molecular pathogenesis of hdv infection remains poorly understood. to advance our understanding of the relationship between hdv infection and liver cancer, it was determined whether hdv could infect in vivo the cells of hepadnavirus-induced hepatocellular carcinoma (hcc). woodchucks (marmota monax) that were chronically infected with hbv-r ...201222334419
modulation of regulatory t-cell activity in combination with interleukin-12 increases hepatic tolerogenicity in woodchucks with chronic hepatitis b.regulatory t cells (treg) play a critical role in the modulation of immune responses to viral antigens in chronic viral hepatitis. woodchucks (marmota monax) infected with the woodchuck hepatitis virus (whv) represent the best animal model for chronic hepatitis b virus (hbv) infection. examination of intrahepatic and peripheral treg in uninfected and whv chronically infected woodchucks showed a significant increase of intrahepatic treg numbers in chronically infected animals, whereas no differen ...201222334260
long-term efficacy of 10-12 years after being immunized with chinese hamster ovary cell derived hepatitis b vaccine in chinese rural communities.to evaluate the long-term efficacy of chinese hamster ovary (cho) cell derived hepatitis b vaccine in country community in china.201222296954
perspectives for a vaccine against hepatitis delta virus.hepatitis delta virus (hdv) causes severe hepatitis in carriers of hepatitis b virus (hbv). in ~90% of patients, hdv persists together with hbv and causes early development of cirrhosis and liver carcinoma. worldwide ~15 million people are coinfected with hbv-hdv. specific defects in the immune response causing persistence of the virus have not been identified. several approaches to develop a vaccine to prevent superinfection in the preclinical model of the woodchuck have failed. recent findings ...201222932974
experimental chronic hepatitis b infection of neonatal tree shrews (tupaia belangeri chinensis): a model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans.hepatitis b virus (hbv) infection continues to be an escalating global health problem. feasible and effective animal models for hbv infection are the prerequisite for developing novel therapies for this disease. the tree shrew (tupaia) is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. whether tree shrews could be chronically infected with hbv in vivo has been controversial for decades. most published research has been repor ...201222913805
recombinant semliki forest virus vectors encoding hepatitis b virus small surface and pre-s1 antigens induce broadly reactive neutralizing antibodies.most hepatitis b virus (hbv) vaccines consist of viral small surface (s) protein subtype adw2 expressed in yeast cells. in spite of good efficacy, hbv-genotype and subtype differences, escape mutants and insufficient th1 activation remain potential problems. to address these problems, we generated recombinant semliki forest virus (rsfv) vectors encoding s protein, subtype adw2 or ayw2, or a fragment of the large surface protein, amino acids 1-48 of the pre-s1 domain, fused to s (pre-s1.1-48/s). ...201222863271
evaluation of heterologous vaginal shiv sf162p4 infection following vaccination with a polyvalent clade b virus-like particle vaccine.the vast diversity of hiv-1 infections has greatly impeded the development of a successful hiv-1/aids vaccine. previous vaccine work has demonstrated limited levels of protection against shiv/siv infection, but protection was observed only when the challenge virus was directly matched to the vaccine strain. as it is likely impossible to directly match the vaccine strain to all infecting strains in nature, it is necessary to develop an hiv-1 vaccine that can protect against a heterologous viral c ...201222214267
identification of an intrahepatic transcriptional signature associated with self-limiting infection in the woodchuck model of hepatitis b.the woodchuck model of hepatitis b virus (hbv) infection displays many characteristics of human infection and has particular value for characterizing the host immune responses during the development of chronic infection. using the newly developed custom woodchuck microarray platform, we compared the intrahepatic transcriptional profiles of neonatal woodchucks with self-limiting woodchuck hepatitis virus (whv) infection to those woodchucks progressing to persistent whv infection. this revealed th ...201322806943
repeated exposure to trace amounts of woodchuck hepadnavirus induces molecularly evident infection and virus-specific t cell response in the absence of serological infection markers and hepatitis.exposure to multiple small doses of hepatitis b virus (hbv) is a frequent occurrence in high-risk groups, including close relatives of infected individuals, primary care givers, and intravenous drug users. it remains uncertain whether such repeated contact may culminate in a symptomatic infection coinciding with hepatitis in individuals not immunoprotected. in this study, we evaluated consequences of multiple exposures to small, liver-nonpathogenic amounts of infectious hepadnavirus in the woodc ...201323135718
dna vaccine cocktail expressing genotype a and c hbv surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and rhesus macaques.there are well over a quarter of a billion chronic hepatitis b virus (hbv) carriers across the globe. most carriers are at high risk for development of liver cirrhosis and subsequent progression to hepatocellular carcinoma. it is therefore imperative to develop new approaches for immunotherapy against this infection. antibodies and cytotoxic t cells to different hbv antigens are believed to be important for reducing viral load and clearing hbv-infected cells from the liver. some of the major cha ...201324310062
pathology in practice. b virus infection in a rhesus macaque. 201323600779
suboptimal protection against h5n1 highly pathogenic avian influenza viruses from vietnam in ducks vaccinated with commercial poultry vaccines.domestic ducks are the second most abundant poultry species in many asian countries including vietnam, and play a critical role in the epizootiology of h5n1 highly pathogenic avian influenza (hpai) [fao]. in this study, we examined the protective efficacy in ducks of two commercial h5n1 vaccines widely used in vietnam; re-1 containing a/goose/guangdong/1/1996 hemagglutinin (ha) clade 0 antigens, and re-5 containing a/duck/anhui/1/2006 ha clade 2.3.4 antigens. ducks received two doses of either v ...201323994373
identification of rodent homologs of hepatitis c virus and pegiviruses.hepatitis c virus (hcv) and human pegivirus (hpgv or gb virus c) are globally distributed and infect 2 to 5% of the human population. the lack of tractable-animal models for these viruses, in particular for hcv, has hampered the study of infection, transmission, virulence, immunity, and pathogenesis. to address this challenge, we searched for homologous viruses in small mammals, including wild rodents. here we report the discovery of several new hepaciviruses (hcv-like viruses) and pegiviruses ( ...201323572554
alpha-interferon suppresses hepadnavirus transcription by altering epigenetic modification of cccdna minichromosomes.covalently closed circular dna (cccdna) of hepadnaviruses exists as an episomal minichromosome in the nucleus of infected hepatocyte and serves as the transcriptional template for viral mrna synthesis. elimination of cccdna is the prerequisite for either a therapeutic cure or immunological resolution of hbv infection. although accumulating evidence suggests that inflammatory cytokines-mediated cure of virally infected hepatocytes does occur and plays an essential role in the resolution of an acu ...201324068929
possible origins and evolution of the hepatitis b virus (hbv).all members of the family hepadnaviridae are primarily viruses which contain double-stranded dna genomes that are replicated via reverse transcription of a pregenomic rna template. there are two subgroups within this family: mammalian and avian. the avian member's include the duck hepatitis b virus (dhbv), heron hepatitis b virus, ross goose hepatitis b virus, stork hepatitis b virus and the recently identified parrot hepatitis b virus. more recently, the detection of endogenous avian hepadnavir ...201324013024
concerted action of activation-induced cytidine deaminase and uracil-dna glycosylase reduces covalently closed circular dna of duck hepatitis b virus.covalently closed circular dna (cccdna) forms a template for the replication of hepatitis b virus (hbv) and duck hbv (dhbv). recent studies suggest that activation-induced cytidine deaminase (aid) functions in innate immunity, although its molecular mechanism of action remains unclear, particularly regarding hbv restriction. here we demonstrated that overexpression of chicken aid caused hypermutation and reduction of dhbv cccdna levels. inhibition of uracil-dna glycosylase (ung) by ung inhibitor ...201323954625
sulfamoylbenzamide derivatives inhibit the assembly of hepatitis b virus nucleocapsids.chronic hepatitis b virus (hbv) infection, a serious public health problem leading to cirrhosis and hepatocellular carcinoma, is currently treated with either pegylated alpha interferon (pegifn-α) or one of the five nucleos(t)ide analogue viral dna polymerase inhibitors. however, neither pegifn-α nor nucleos(t)ide analogues are capable of reliably curing the viral infection. in order to develop novel antiviral drugs against hbv, we established a cell-based screening assay by using an immortalize ...201323576513
chimeric hepatitis b virus/hepatitis c virus envelope proteins elicit broadly neutralizing antibodies and constitute a potential bivalent prophylactic vaccine.the development of a prophylactic vaccine against hepatitis c virus (hcv) has become an important medical priority, because 3-4 million new hcv infections are thought to occur each year worldwide. hepatitis b virus (hbv) is another major human pathogen, but infections with this virus can be prevented with a safe, efficient vaccine, based on the remarkable ability of the envelope protein (s) of this virus to self-assemble into highly immunogenic subviral particles. chimeric hbv-hcv envelope prote ...201323150224
histopathological changes in the liver of tree shrew (tupaia belangeri chinensis) persistently infected with hepatitis b virus.an animal model for hbv that more closely approximates the disease in humans is needed. the tree shrew (tupaia belangeri) is closely related to primates and susceptible to hbv. we previously established that neonatal tree shrews can be persistently infected with hbv in vivo, and here present a six year follow-up histopathological study of these animals.201324220021
bats carry pathogenic hepadnaviruses antigenically related to hepatitis b virus and capable of infecting human hepatocytes.the hepatitis b virus (hbv), family hepadnaviridae, is one of most relevant human pathogens. hbv origins are enigmatic, and no zoonotic reservoirs are known. here, we screened 3,080 specimens from 54 bat species representing 11 bat families for hepadnaviral dna. ten specimens (0.3%) from panama and gabon yielded unique hepadnaviruses in coancestral relation to hbv. full genome sequencing allowed classification as three putative orthohepadnavirus species based on genome lengths (3,149-3,377 nt), ...201324043818
unraveling the complexity of hepatitis b virus: from molecular understanding to therapeutic strategy in 50 years.hepatitis b virus (hbv) is a well-known hepadnavirus with a double-stranded circular dna genome. although hbv was first described approximately 50 years ago, the precise mechanisms of hbv infection and effective therapeutic strategies remain unclear. here, we focus on summarizing the complicated mechanisms of hbv replication and infection, as well as genomic factors and epigenetic regulation. additionally, we discuss in vivo models of hbv, as well as diagnosis, prevention and therapeutic drugs f ...201323819994
combination of dna prime--adenovirus boost immunization with entecavir elicits sustained control of chronic hepatitis b in the woodchuck model.a potent therapeutic t-cell vaccine may be an alternative treatment of chronic hepatitis b virus (hbv) infection. previously, we developed a dna prime-adenovirus (adv) boost vaccination protocol that could elicit strong and specific cd8+ t-cell responses to woodchuck hepatitis virus (whv) core antigen (whcag) in mice. in the present study, we first examined whether this new prime-boost immunization could induce whcag-specific t-cell responses and effectively control whv replication in the whv-tr ...201323785279
persistent human hepatitis b virus infection in cynomolgus monkeys: a novel animal model in the search for a cure? 201323775673
molecular characterization of woodchuck cd4 (wcd4) and production of a depletion monoclonal antibody against wcd4.cd4 t cells play an important role in the immune response against hepatitis b virus (hbv) infection. woodchucks represent an excellent animal model to study hbv infection. in this study, we characterized the cdna sequence of woodchuck cd4 (wcd4). the deduced wcd4 protein has four extracellular immunoglobulin-like domains comparable to the other mammalian cd4 molecules. the important extracellular cysteine residues and the intracellular tyrosine protein kinase-binding site of wcd4 are also conser ...201323685260
molecular determinants of hepatitis b and d virus entry restriction in mouse sodium taurocholate cotransporting polypeptide.human hepatitis b virus (hbv) and its satellite virus, hepatitis d virus (hdv), primarily infect humans, chimpanzees, or tree shrews (tupaia belangeri). viral infections in other species are known to be mainly restricted at the entry level since viral replication can be achieved in the cells by transfection of the viral genome. sodium taurocholate cotransporting polypeptide (ntcp) is a functional receptor for hbv and hdv, and amino acids 157 to 165 of ntcp are critical for viral entry and likely ...201323678176
prime/boost immunization with dna and adenoviral vectors protects from hepatitis d virus (hdv) infection after simultaneous infection with hdv and woodchuck hepatitis virus.hepatitis d virus (hdv) superinfection of hepatitis b virus (hbv) carriers causes severe liver disease and a high rate of chronicity. therefore, a vaccine protecting hbv carriers from hdv superinfection is needed. to protect from hdv infection an induction of virus-specific t cells is required, as antibodies to the two proteins of hdv, p24 and p27, do not neutralize the hbv-derived envelope of hdv. in mice, hdv-specific cd8(+) and cd4(+) t cell responses were induced by a dna vaccine expressing ...201323637419
occult hepatitis b virus infection in chacma baboons, south africa.during previous studies of susceptibility to hepatitis b virus (hbv) infection, hbv dna was detected in 2/6 wild-caught baboons. in the present study, hbv dna was amplified from 15/69 wild-caught baboons. all animals were negative for hbv surface antigen and antibody against hbv core antigen. liver tissue from 1 baboon was immunohistochemically negative for hbv surface antigen but positive for hbv core antigen. the complete hbv genome of an isolate from this liver clustered with subgenotype a2. ...201323631817
expression of matrix metalloproteinases and their inhibitors in the woodchuck model of hepatocellular carcinoma.matrix metalloproteinases (mmps) play a central role in tumor invasion and metastasis. increased expression of mmps occurs during development of hepatocellular carcinoma (hcc) in humans following infection with hepatitis b virus (hbv). woodchucks are used as an animal model for hepadnavirus-induced hcc. all woodchucks infected chronically with woodchuck hepatitis virus (whv), a virus that is closely related to hbv, develop hcc. in the present study mmps and related molecules were investigated in ...201323595580
novel recombinant hepatitis b virus vectors efficiently deliver protein and rna encoding genes into primary hepatocytes.hepatitis b virus (hbv) has extremely restricted host and hepatocyte tropism. hbv-based vectors could form the basis of novel therapies for chronic hepatitis b and other liver diseases and would also be invaluable for the study of hbv infection. previous attempts at developing hbv-based vectors encountered low yields of recombinant viruses and/or lack of sufficient infectivity/cargo gene expression in primary hepatocytes, which hampered follow-up applications. in this work, we constructed a nove ...201323552416
discovery of naturally occurring transmissible chronic hepatitis b virus infection among macaca fascicularis from mauritius island.despite a high prevalence of hepatitis b virus (hbv) infection in endangered apes, no hbv infection has been reported in small, old-world monkeys. in search for a small, nonhuman primate model, we investigated the prevalence of hbv infection in 260 macaque (cercopithecidae) sera of various geographical origins (i.e., morocco, mauritius island, and asia). hbv-positive markers were detected in cynomolgus macaques (macaca fascicularis) from mauritius island only, and, remarkably, hbv dna was positi ...201323536484
deregulation of epigenetic mechanisms by the hepatitis b virus x protein in hepatocarcinogenesis.this review focuses on the significance of deregulation of epigenetic mechanisms by the hepatitis b virus (hbv) x protein in hepatocarcinogenesis and hbv replication. epigenetic mechanisms, dna methylation, and specific histone modifications, e.g., trimethylation of h3 on lysine-27 or lysine-4, maintain 'cellular memory' by silencing expression of lineage-inducing factors in stem cells and conversely, of pluripotency factors in differentiated cells. the x protein has been reported to induce expr ...201323507839
avihepadnavirus diversity in parrots is comparable to that found amongst all other avian species.avihepadnaviruses have previously been isolated from various species of duck, goose, stork, heron and crane. recently the first parrot avihepadnavirus was isolated from a ring-necked parakeet in poland. in this study, 41 psittacine liver samples archived in poland over the last nine years were tested for presence of parrot hepatitis b virus (phbv). we cloned and sequenced phbv isolates from 18 birds including a crimson rosella, an african grey parrot and sixteen ring-necked parakeets. phbv isola ...201323411008
preclinical evaluation of a two-dose vaccination schedule of recombinant hansenula polymorpha hepatitis b vaccine in animals.the current 3-dose regimen of hepatitis b vaccination for infants requiring over 6 mo period may pose the poor rate of compliance and later protection from hepatitis b virus (hbv) infection. this preclinical study is to investigate the feasibility of reducing the number of doses of hepatitis b (hb) vaccine.201323370192
hepatitis b virus hepatotropism is mediated by specific receptor recognition in the liver and not restricted to susceptible hosts.the human hepatitis b virus (hbv) causes acute and chronic infections in humans and chimpanzees. hbv infects its hosts at minimal inoculation doses and replicates exclusively in hepatocytes. the viral determinants for the pronounced species specificity and the high efficacy to address hepatocytes in vivo are unknown. previous findings showed that n-terminally myristoylated peptides constituting a receptor binding domain of the hbv large envelope (l)-protein block hbv entry in vitro and in vivo. ...201323292963
novel ssdna viruses discovered in yellow-crowned parakeet (cyanoramphus auriceps) nesting material.during routine monitoring of yellow-crowned parakeets in the poulter valley of the south island of new zealand, a dead parakeet chick was discovered in a nest. known parrot-infecting viruses, such as beak and feather disease virus (bfdv), avian polyomavirus (apv), and parrot hepatitis b virus (phbv), were not detected in the nesting material. however, we recovered two novel single-stranded dna viruses (ssdna), cynncxv (2308 nt) and cynnckv (2087 nt), which have genome architectures similar to th ...201323417396
involvement of the host dna-repair enzyme tdp2 in formation of the covalently closed circular dna persistence reservoir of hepatitis b viruses.hepatitis b virus (hbv), the causative agent of chronic hepatitis b and prototypic hepadnavirus, is a small dna virus that replicates by protein-primed reverse transcription. the product is a 3-kb relaxed circular dna (rc-dna) in which one strand is linked to the viral polymerase (p protein) through a tyrosyl-dna phosphodiester bond. upon infection, the incoming rc-dna is converted into covalently closed circular (ccc) dna, which serves as a viral persistence reservoir that is refractory to curr ...201425201958
[antibody persistence following booster vaccination with three doses of hepatitis b vaccines among low-response adults in zhangqiu county of shandong province: 24-month of follow-up from 2009].to assess the 24-month efficacy after booster vaccination with 3 doses of hepatitis b vaccine among low-response adults in zhangqiu county of shandong province.201425619213
potential mechanisms of hepatitis b virus induced liver injury.chronic active hepatitis (cah) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma. the histological end points of cah are chronic inflammation, fibrosis and cirrhosis which are coupled with increased dna synthesis in cirrhotic vs healthy normal livers. the potential mechanism involved in cah includes a combination of processes leading to liver cell necrosis, inflammation and cytokine production and liver scaring (fibrosis). the severity ...201425253946
genome sequence of a pathogenic isolate of monkey b virus (species macacine herpesvirus 1).the only genome sequence for monkey b virus (bv; species macacine herpesvirus 1) is that of an attenuated vaccine strain originally isolated from a rhesus monkey (bvrh). here we report the genome sequence of a virulent bv strain isolated from a cynomolgus macaque (bvcy). the overall genome organization is the same, although sequence differences exist. the greatest sequence divergence is located in non-coding areas of the long and short repeat regions. like bvrh, bvcy has duplicated ori elements ...201424903602
multiple antibody targets on herpes b glycoproteins b and d identified by screening sera of infected rhesus macaques with peptide microarrays.herpes b virus (or herpesvirus simiae or macacine herpesvirus 1) is endemic in many populations of macaques, both in the wild and in captivity. the virus elicits only mild clinical symptoms (if any) in monkeys, but can be transmitted by various routes, most commonly via bites, to humans where it causes viral encephalitis with a high mortality rate. hence, herpes b constitutes a considerable occupational hazard for animal caretakers, veterinarians and laboratory personnel. efforts are therefore b ...201424497986
a polyvalent clade b virus-like particle hiv vaccine combined with partially protective oral preexposure prophylaxis prevents simian-human immunodeficiency virus infection in macaques and primes for virus-amplified immunity.vaccination and preexposure prophylaxis (prep) with antiretrovirals have shown only partial protection from hiv-1 infection in human trials. oral truvada (emtricitabine/tenofovir disoproxil fumarate) is fda approved as prep but partial adherence reduces efficacy. if combined as biomedical preventions (cbp), an hiv vaccine could protect when prep adherence is low and prep could prevent vaccine breakthroughs. the efficacy of combining oral prep with an hiv vaccine has not been evaluated in humans. ...201424914761
animal models for influenza virus pathogenesis, transmission, and immunology.in humans, infection with an influenza a or b virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. however, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. disease severity depends upon the virulence of the influenza virus strain and the immune competence and pre ...201424709389
variability in the precore and core promoter region of the hepatitis b virus genome.there is increasing evidence that hepatitis b virus (hbv) infections with different genotypes and subgenotypes differ in response to treatment and long-term prognosis. the differences emerge from variability within the genomes that leads to structural deviations at the pregenomic level and to changes at the translational level. naturally occurring hbv strains covering the four major genotypes a-d were obtained from 393 patients and part of the genome was amplified using polymerase chain reaction ...201424249691
modulation of hepatitis b surface antigen secretion by annexin ii expressed in hepatitis b virus‑producing hepatoma cells.the role of annexin ii in hepatitis b virus (hbv)‑associated hepatocellular carcinoma (hcc) remains to be elucidated. intracellular hepatitis b surface antigen (hbsag)‑retention contributes to the induction of hepatocarcinogenesis. the present study aimed to investigate the regulation of hbsag secretion by annexin ii expressed in hbv‑producing hepatoma cells. the expression of annexin ii was analyzed using western blot analysis in smmc‑7721, hepg2, hepg2.2.15, 293t and chinese hamster ovary (cho ...201425270731
structurally similar woodchuck and human hepadnavirus core proteins have distinctly different temperature dependences of assembly.woodchuck hepatitis virus (whv), a close relative of human hepatitis b virus (hbv), has been a key model for disease progression and clinical studies. sequences of the assembly domain of whv and hbv core proteins (wcp149 and hcp149, respectively) have 65% identity, suggesting similar assembly behaviors. we report a cryo-electron microscopy (cryo-em) structure of the whv capsid at nanometer resolution and characterization of wcp149 assembly. at this resolution, the t=4 capsid structures of whv an ...201425253350
primary seronegative but molecularly evident hepadnaviral infection engages liver and induces hepatocarcinoma in the woodchuck model of hepatitis b.hepadnavirus at very low doses establishes in woodchucks asymptomatic, serologically undetectable but molecularly evident persistent infection. this primary occult infection (poi) preferentially engages the immune system and initiates virus-specific t cell response in the absence of antiviral antibody induction. the current study aimed to determine whether poi with time may culminate in serologically identifiable infection and hepatitis, and what are, if any, its pathological consequences. juven ...201425165821
tupaia belangeri as an experimental animal model for viral infection.tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. the morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the tupaiidae. genomic analysis has revealed that the genus tupaia is closer to humans than it is to rodents. in addition, tupaias are susceptible to hepatitis b virus and hepatitis c virus. the only othe ...201425048261
[expressions and significance of tlr2 and tlr4 in kupffer cells of tree shrews chronically infected with hepatitis b virus].to investigate the mrna expression levels of toll-like receptors 2 (tlr2) and tlr4 in kupffer cells of tree shrews that were chronically infected with hepatitis b virus (hbv), and the effects of these receptors on the function of kupffer cells.201425001929
kinetics of the bile acid transporter and hepatitis b virus receptor na+/taurocholate cotransporting polypeptide (ntcp) in hepatocytes.the human liver bile acid transporter na(+)/taurocholate cotransporting polypeptide (ntcp) has recently been identified as liver-specific receptor for infection of hepatitis b virus (hbv), which attaches via the myristoylated pres1 (myr-pres1) peptide domain of its large surface protein to ntcp. since binding of the myr-pres1 peptide to ntcp is an initiating step of hbv infection, we investigated if this process interferes with the physiological bile acid transport function of ntcp.201424845614
advances and challenges in the development of therapeutic dna vaccines against hepatitis b virus infection.despite the existence of an effective prophylactic vaccine, chronic hepatitis b virus (hbv) infection remains a major public health problem. because very weak and functionally impaired virus-specific immune responses play a key role in the persistence of hbv infection, the stimulation of these responses appears to be of particular importance for virus clearance. in this regard dna-based vaccination has emerged as novel, promising therapeutic approach for chronic hepatitis b. this review provides ...201424828255
transplacental transfer of hepatitis b neutralizing antibody during pregnancy in an animal model: implications for newborn and maternal health.despite the success of postexposure prophylaxis (pep) of the newborn in preventing mother-to-child transmission of hepatitis b virus), in non-us clinical trials, administering hepatitis b immune globulin (hbig) to mothers at the end of pregnancy (in addition to passive-active pep of the newborn) only partially improved outcomes. that is, a significant percentage of newborns became infected during their first year of life. we used a relevant animal model for human igg transplacental transfer to s ...201424800066
strategies to inhibit entry of hbv and hdv into hepatocytes.although there has been much research into the pathogenesis and treatment of hepatitis b virus (hbv) and hepatitis d virus (hdv) infections, we still do not completely understand how these pathogens enter hepatocytes. this is because in vitro infection studies have only been performed in primary human hepatocytes. development of a polarizable, hbv-susceptible human hepatoma cell line and studies of primary hepatocytes from tupaia belangeri have provided important insights into the viral and cell ...201424768844
nucleoside analogues alone or combined with vaccination prevent hepadnavirus viremia and induce protective immunity: alternative strategy for hepatitis b virus post-exposure prophylaxis.the current strategies for hepatitis b virus (hbv) post-exposure prophylaxis (pep) are not generally available in remote and rural areas of developing countries and/or carry potential risks for infection with blood-borne transmitted pathogens. nucleotide analogues (nas) are successfully used for human immunodeficiency virus pep, and maybe effective for hbv pep. in this study, we tested the na-based strategies for hbv pep using the chinese woodchuck model.201424583157
ntcp and beyond: opening the door to unveil hepatitis b virus entry.chronic hepatitis b virus (hbv) infection, affecting approximately 240 million people worldwide, is a major public health problem that elevates the risk of developing liver cirrhosis and hepatocellular carcinoma. given that current anti-hbv drugs are limited to interferon-based regimens and nucleos(t)ide analogs, the development of new anti-hbv agents is urgently needed. the viral entry process is generally an attractive target implicated in antiviral strategies. using primary cells from humans ...201424557582
enhancing virus-specific immunity in vivo by combining therapeutic vaccination and pd-l1 blockade in chronic hepadnaviral infection.hepatitis b virus (hbv) persistence is facilitated by exhaustion of cd8 t cells that express the inhibitory receptor programmed cell death-1 (pd-1). improvement of the hbv-specific t cell function has been obtained in vitro by inhibiting the pd-1/pd-ligand 1 (pd-l1) interaction. in this study, we examined whether in vivo blockade of the pd-1 pathway enhances virus-specific t cell immunity and leads to the resolution of chronic hepadnaviral infection in the woodchuck model. the woodchuck pd-1 was ...201424391505
microrna expression in hepatitis b virus infected primary treeshrew hepatocytes and the independence of intracellular mir-122 level for de novo hbv infection in culture.infection of hepatitis b virus (hbv) in hepatocytes has been known to be controlled by multiple cellular factors, while the relationship of the infection and liver micrornas remains obscure. in this study, a mirna database, containing 168 unique mature mirna members from primary hepatocytes of a primate-like animal, northern treeshrew (tupaia belangeri) that is the only species susceptible for hbv infection other than human and chimpanzee, was established. the relative level of a liver predomina ...201424314655
asymptomatic hepadnaviral persistence and its consequences in the woodchuck model of occult hepatitis b virus infection.woodchuck hepatitis virus (whv) is molecularly and pathogenically closely related to hepatitis b virus (hbv). both viruses display tropism towards hepatocytes and cells of the immune system and cause similar liver pathology, where acute hepatitis can progress to chronic hepatitis and to hepatocellular carcinoma (hcc). two forms of occult hepadnaviral persistence were identified in the woodchuck-whv model: secondary occult infection (soi) and primary occult infection (poi). soi occurs after resol ...201526623268
recombinant subgroup b human respiratory syncytial virus expressing enhanced green fluorescent protein efficiently replicates in primary human cells and is virulent in cotton rats.human respiratory syncytial virus (hrsv) is the most important viral cause of severe respiratory tract disease in infants. two subgroups (a and b) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. existing in vitro and in vivo models of hrsv focus almost exclusively on subgroup a viruses. here, a recombinant (r) subgroup b virus (rhrsv(b05)) was generated based on a consensus genome sequence obtained directly from an unpas ...201525540371
macacine herpesvirus 1 in long-tailed macaques, malaysia, 2009-2011.macacine herpesvirus 1 (mahv1; b virus) naturally infects macaques (macaca spp.) and can cause fatal encephalitis in humans. in peninsular malaysia, wild macaques are abundant, and translocation is used to mitigate human-macaque conflict. most adult macaques are infected with mahv1, although the risk for transmission to persons who handle them during capture and translocation is unknown. we investigated mahv1 shedding among 392 long-tailed macaques (m. fascicularis) after capture and translocati ...201526080081
construction of polyomavirus-derived pseudotype virus-like particles displaying a functionally active neutralizing antibody against hepatitis b virus surface antigen.virus-like particles (vlps) can be efficiently produced by heterologous expression of viral structural proteins in yeast. due to their repetitive structure, vlps are extensively used for protein engineering and generation of chimeric vlps with inserted foreign epitopes. hamster polyomavirus vp1 represents a promising epitope carrier. however, insertion of large sized protein sequences may interfere with its self-assembly competence. the co-expression of polyomavirus capsid protein vp1 with minor ...201526370129
the woodchuck, a nonprimate model for immunopathogenesis and therapeutic immunomodulation in chronic hepatitis b virus infection.the woodchuck hepatitis virus (whv) and its host, the eastern woodchuck, is a very valuable model system for hepatitis b virus infection. many aspects of whv replication and pathogenesis resemble acute and chronic hepatitis b infection in patients. since the establishment of immunological tools, woodchucks were used to develop new therapeutic vaccines and immunomodulatory approaches to treat chronic hepadnaviral infections. combination therapy of nucleos(t)ide analogs, with prime-boost vaccinati ...201526511761
current status of immunomodulatory therapy in chronic hepatitis b, fifty years after discovery of the virus: search for the "magic bullet" to kill cccdna.chronic hepatitis b (chb) is currently treated with ifn-α and nucleos(t)ide analogues, which have many clinical benefits, but there is no ultimate cure. the major problem consists in the persistence of cccdna in infected hepatocytes. because no antiviral drug has been evaluated which significantly reduces copies of cccdna, cytolytic and noncytolytic approaches are needed. effective virus-specific t- and b-cell responses remain crucial in eliminating cccdna-carrying hepatocytes and for the long-t ...201526476376
intrahepatic transcriptional signature associated with response to interferon-α treatment in the woodchuck model of chronic hepatitis b.recombinant interferon-alpha (ifn-α) is an approved therapy for chronic hepatitis b (chb), but the molecular basis of treatment response remains to be determined. the woodchuck model of chronic hepatitis b virus (hbv) infection displays many characteristics of human disease and has been extensively used to evaluate antiviral therapeutics. in this study, woodchucks with chronic woodchuck hepatitis virus (whv) infection were treated with recombinant woodchuck ifn-α (wifn-α) or placebo (n = 12/grou ...201526352406
mouse models of hepatitis b virus pathogenesis.the host range of hepatitis b virus (hbv) is limited to humans and chimpanzees. as discussed in the literature, numerous studies in humans and chimpanzees have generated a great deal of information on the mechanisms that cause viral clearance, viral persistence, and disease pathogenesis during acute or chronic hbv infection. relevant pathogenetic studies have also been performed in those few species representing natural hosts of hepadnaviruses that are related to hbv, such as the woodchuck hepat ...201526292984
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