Publications

TitleAbstractYear
Filter
PMID
Filter
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
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
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
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
molecular characterization of woodchuck ifi16 and aim2 and their expression in woodchucks infected with woodchuck hepatitis virus (whv).ifi16 and aim2 are important dna sensors in antiviral immunity. to characterize these two molecules in a woodchuck model, which is widely used to study hepatitis b virus (hbv) infection, we cloned and analyzed the complete coding sequences (cdss) of woodchuck ifi16 and aim2, and found that aim2 was highly conserved in mammals, whereas the degree of sequence identity between woodchuck ifi16 and its mammalian orthologues was low. ifi16 and ifn-β were upregulated following vacv ds 70 mer transfecti ...201627354260
origins and evolution of hepatitis b virus and hepatitis d virus.members of the family hepadnaviridae fall into two subgroups: mammalian and avian. the detection of endogenous avian hepadnavirus dna integrated into the genomes of zebra finches has revealed a deep evolutionary origin of hepadnaviruses that was not previously recognized, dating back at least 40 million and possibly >80 million years ago. the nonprimate mammalian members of the hepadnaviridae include the woodchuck hepatitis virus (whv), the ground squirrel hepatitis virus, and arctic squirrel he ...201626729756
hepatitis virus infections in poultry.viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis e virus (hev), duck hepatitis b virus (dhbv), duck hepatitis a virus (dhav-1, -2, -3), duck hepatitis virus types 2 and 3, fowl adenoviruses (fadv), and turkey hepatitis virus (thv). while these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. in this article, we aim to review the common an ...201627610716
avian polyomavirus genome sequences recovered from parrots in captive breeding facilities in poland.eight genomes of avian polyomaviruses (apvs) were recovered and sequenced from deceased psittacula eupatria, psittacula krameri, and melopsittacus undulatus from various breeding facilities in poland. of these apv-positive samples, six had previously tested positive for beak and feather disease virus (bfdv) and/or parrot hepatitis b virus (phbv).201526404592
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
a metagenomics and case-control study to identify viruses associated with bovine respiratory disease.bovine respiratory disease (brd) is a common health problem for both dairy and beef cattle, resulting in significant economic loses. in order to identify viruses associated with brd, we used a metagenomics approach to enrich and sequence viral nucleic acids in the nasal swabs of 50 young dairy cattle with symptoms of brd. following deep sequencing, de novo assembly, and translated protein sequence similarity searches, numerous known and previously uncharacterized viruses were identified. bovine ...201525740998
sleeping beauty transposon system for genetic etiological research and gene therapy of cancers.carcinogenesis is etiologically associated with somatic mutations of critical genes. recently, a number of somatic mutations and key molecules have been found to be involved in functional networks affecting cancer progression. suitable animal models are required to validate cancer-promoting or -inhibiting capacities of these mutants and molecules. sleeping beauty transposon system consists of a transposon that carries gene(s) of interest and a transposase that recognizes, excises, and reinserts ...201525455252
present and future dna vaccines for chronic hepatitis b treatment.with at least 240 million hepatitis b virus (hbv) carriers worldwide, being at a high risk of cirrhosis and hepatocellular carcinoma (hcc), chronic hepatitis b remains a major public health issue. because current antiviral treatments are only virostatic, there is an urgent need for the development of innovative anti-hbv strategies leading to the functional cure. in this context, dna-based vaccines appear as a promising approach. area covered: in this review, the authors summarize the pertinent f ...201727892722
nuclear factor y regulates ancient budgerigar hepadnavirus core promoter activity.endogenous viral elements (eve) in animal genomes are the fossil records of ancient viruses and provide invaluable information on the origin and evolution of extant viruses. extant hepadnaviruses include avihepadnaviruses of birds and orthohepadnaviruses of mammals. the core promoter (cp) of hepadnaviruses is vital for viral gene expression and replication. we previously identified in the budgerigar genome two eves that contain the full-length genome of an ancient budgerigar hepadnavirus (ebhbv1 ...201627501758
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
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
evaluation of the activity of lamivudine and zidovudine against ebola virus.in the fall of 2014, an international news agency reported that patients suffering from ebola virus disease (evd) in liberia were treated successfully with lamivudine, an antiviral drug used to treat human immunodeficiency virus-1 and hepatitis b virus infections. according to the report, 13 out of 15 patients treated with lamivudine survived and were declared free from ebola virus disease. in this study, the anti-ebola virus (ebov) activity of lamivudine and another antiretroviral, zidovudine, ...201627902714
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
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
development of recombinant vaccine against a(h1n1) 2009 influenza based on virus-like nanoparticles carrying the extracellular domain of m2 protein.the conventional vaccines currently being used to deal with influenza are based on a virus obtained in chicken embryos or its components. the high variability of the major immunogenic surface proteins - hemagglutinin and neuraminidase-require the development of strain-specific vaccines that match the antigenic specificity of a newly emerging virus. recombinant vaccines based on single viral proteins that could be easily produced in standard expression systems are attractive alternatives to tradi ...201022649643
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
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
sialic acid content in human saliva and anti-influenza activity against human and avian influenza viruses.it was shown previously that human saliva has higher antiviral activity against human influenza viruses than against h5n1 highly pathogenic avian influenza viruses, and that the major anti-influenza activity was associated with sialic-acid-containing molecules. to further characterize the differential susceptibility to saliva among influenza viruses, seasonal influenza a and b virus, pandemic h1n1 virus, and 15 subtypes of avian influenza virus were tested for their susceptibility to human and c ...201626671828
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
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
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
low hepatitis b virus-specific t-cell response in males correlates with high regulatory t-cell numbers in murine models.hepatitis b virus (hbv) infection shows significant gender-related differences in pathogenesis, disease progression, and development of hepatocellular carcinoma. the gender-associated differences in hbv replication and viral protein levels may be associated with distinct hbv-specific immune responses in the host. in the present study, we examined the impact of gender on hbv-specific immune responses in two different mouse models representing transient and persistent hepadnaviral infection; hydro ...201728295453
prevention of liver tumor formation in woodchucks with established hepatocellular carcinoma by treatment with cationic liposome-dna complexes.approximately 250 million people worldwide are chronically infected with hepatitis b virus (hbv) and more than half of the hepatocellular carcinoma (hcc) cases are attributed to this infection. as hcc has a high mortality rate, and current treatment options are remarkably limited, the development of new therapeutic treatment strategies is warranted.201728264666
prec and c regions of woodchuck hepatitis virus facilitate persistent expression of surface antigen of chimeric whv-hbv virus in the hydrodynamic injection balb/c mouse model.in the hydrodynamic injection (hi) balb/c mouse model with the overlength viral genome, we have found that woodchuck hepatitis virus (whv) could persist for a prolonged period of time (up to 45 weeks), while hepatitis b virus (hbv) was mostly cleared at week four. in this study, we constructed a series of chimeric genomes based on hbv and whv, in which the individual sequences of a 1.3-fold overlength hbv genome in pbs-hbv1.3 were replaced by their counterparts from whv. after hi with the whv-hb ...201728230775
woodchuck sodium taurocholate cotransporting polypeptide supports low-level hepatitis b and d virus entry.sodium taurocholate cotransporting polypeptide (ntcp) is the functional receptor for human hepatitis b virus (hbv) and its satellite hepatitis d virus (hdv). species barriers to hbv/hdv infection are mainly determined at entry level by variations in the sequences of particular ntcp orthologs. in this study, we sought to determine whether the ntcp ortholog in woodchuck (marmota monax), woodchuck ntcp (wntcp) supports viral infection. we found that wntcp is capable of supporting hbv/hdv infection ...201728213271
sodium taurocholate cotransporting polypeptide is the limiting host factor of hepatitis b virus infection in macaque and pig hepatocytes.infections with the human hepatitis b (hbv) and hepatitis d virus (hdv) depend on species-specific host factors like the receptor human sodium taurocholate cotransporting polypeptide hntcp. complementation of mouse hepatocytes with hntcp confers susceptibility to hdv but not hbv indicating the requirement of additional hbv-specific factors. as an essential premise towards the establishment for an hbv-susceptible animal model, we investigated the role of hntcp as a limiting factor of hepatocytes ...201728195359
measurement of antiviral effect and innate immune response during treatment of primary woodchuck hepatocytes.an estimated 350 million people are chronically infected with hepatitis b virus (hbv), and over one million people die each year due to hbv-associated liver diseases, such as cirrhosis and liver cancer. current therapeutics for chronic hbv infection are limited to nucleos(t)ide analogs and interferon. these anti-hbv drugs in general reduce viral load and improve the long-term outcome of infection but very rarely lead to a cure. thus, new therapies for chronic hbv infection need to be developed b ...201727975326
diverse activities of viral cis-acting rna regulatory elements revealed using multicolor, long-term, single-cell imaging.cis-acting rna structural elements govern crucial aspects of viral gene expression. how these structures and other posttranscriptional signals affect rna trafficking and translation in the context of single cells is poorly understood. herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral rna regulatory control in individual cells. we apply this strategy to demonstrate differential mrna trafficking behaviors governed by rna elements derived ...201727903772
transcriptome analysis and comparison of marmota monax and marmota himalayana.the eastern woodchuck (marmota monax) is a classical animal model for studying hepatitis b virus (hbv) infection and hepatocellular carcinoma (hcc) in humans. recently, we found that marmota himalayana, an asian animal species closely related to marmota monax, is susceptible to woodchuck hepatitis virus (whv) infection and can be used as a new mammalian model for hbv infection. however, the lack of genomic sequence information of both marmota models strongly limited their application breadth and ...201627806133
prospective population management for hepatitis b in the chimpanzee (pan troglodytes) ssp® population.hepatitis b virus causes horizontally transmitted infectious hepatopathy of primates and may progress to hepatocellular carcinoma. historically, a small number of chimpanzees ( pan troglodytes ) living in accredited north american zoos have been confirmed with positive hepatitis b serology consistent with exposure. however, the overall status for this population and the interpretation of these individual test results have not been established previously. the current u.s. zoo-housed population (n ...201627691953
[the true story and advantages of the famous hepatitis b virus core particles: outlook 2016].this review article is a continuation of the paper "hepatitis b core particles as a universal display model: a structure-function basis for development" written by pumpens p. and grens e., ordered by professor lev kisselev and published in febs letters, 1999, 442, 1-6. the past 17 years have strengthened the paper's finding that the human hepatitis b virus core protein, along with other hepadnaviridae family member core proteins, is a mysterious, multifunctional protein. the core gene of the hep ...201627668597
molecular cloning, characterization and expression analysis of tgf-β and receptor genes in the woodchuck model.transforming growth factor beta (tgf-β) is an important cytokine with pleiotropic regulatory functions in the immune system and in the responses against viral infections. tgf-β acts on a variety of immune cells through the cell surface tgf-β receptor (university of duisburg-essentgfbr). the woodchuck has been used as a biomedical model for studies of obesity and energy balance, endocrine and metabolic function, cardiovascular, cerebrovascular and neoplastic disease. woodchucks infected with wood ...201627637515
extracellular vesicles including exosomes regulate innate immune responses to hepatitis b virus infection.the innate immune system is essential for controlling viral infection. hepatitis b virus (hbv) persistently infects human hepatocytes and causes hepatocellular carcinoma. however, the innate immune response to hbv infection in vivo remains unclear. using a tree shrew animal model, we showed that hbv infection induced hepatic interferon (ifn)-γ expression during early infection. our in vitro study demonstrated that hepatic nk cells produced ifn-γ in response to hbv only in the presence of hepatic ...201627630638
activating the innate immune response to counter chronic hepatitis b virus infection.chronic infection with hepatitis b virus (hbv) is endemic to several populous parts of the world, where resulting complicating cirrhosis and hepatocellular carcinoma occur commonly. licensed drugs to treat the infection have limited curative efficacy, and development of therapies that eliminate all replication intermediates of hbv is a priority. areas covered: the recent demonstration that the activation of the innate immune response may eradicate hbv from infected hepatocytes has a promising th ...201627603796
antiviral efficacy and host innate immunity associated with sb 9200 treatment in the woodchuck model of chronic hepatitis b.sb 9200, an oral prodrug of the dinucleotide sb 9000, is being developed for the treatment of chronic hepatitis b virus (hbv) infection and represents a novel class of antivirals. sb 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (rig-i) and nucleotide-binding oligomerization domain-containing protein 2 (nod2) resulting in interferon (ifn) mediated antiviral immune responses in virus-infected cells. additionally, the binding of sb 9200 to these sensor prote ...201627552102
molecular cloning, characterization and expression analysis of woodchuck retinoic acid-inducible gene i.cytosolic retinoic acid-inducible gene i (rig-i) is an important innate immune rna sensor and can induce antiviral cytokines, e.g., interferon-β (ifn-β). innate immune response to hepatitis b virus (hbv) plays a pivotal role in viral clearance and persistence. however, knowledge of the role that rig-i plays in hbv infection is limited. the woodchuck is a valuable model for studying hbv infection. to characterize the molecular basis of woodchuck rig-i (wrig-i), we analyzed the complete coding seq ...201627376800
characterization of metastatic tumor antigen 1 and its interaction with hepatitis b virus x protein in nf-κb signaling and tumor progression in a woodchuck hepatocellular carcinoma model.the metastatic tumor antigen 1 (mta1) protein is associated with tumor invasiveness and poor prognosis in patients with hepatocellular carcinoma (hcc), particularly in those with hepatitis b virus (hbv)-related hcc. chronically woodchuck hepatitis virus (whv)-infected woodchuck is an ideal animal model for studying the pathogenesis of hbv-associated liver diseases, including hcc. to investigate the roles of mta1 in hbv-associated hepatocarcinogenesis in the woodchuck model, we cloned the woodchu ...201627323415
hepatitis b virus nuclear export elements: rna stem-loop α and β, key parts of the hbv post-transcriptional regulatory element.many viruses contain rna elements that modulate splicing and/or promote nuclear export of their rnas. the rnas of the major human pathogen, hepatitis b virus (hbv) contain a large (~600 bases) composite cis-acting 'post-transcriptional regulatory element' (pre). this element promotes expression from these naturally intronless transcripts. indeed, the related woodchuck hepadnavirus pre (wpre) is used to enhance expression in gene therapy and other expression vectors. these pre are likely to act t ...201627031749
genetic evidence for genotoxic effect of entecavir, an anti-hepatitis b virus nucleotide analog.nucleoside analogues (nas) have been the most frequently used treatment option for chronic hepatitis b patients. however, they may have genotoxic potentials due to their interference with nucleic acid metabolism. entecavir, a deoxyguanosine analog, is one of the most widely used oral antiviral nas against hepatitis b virus. it has reported that entecavir gave positive responses in both genotoxicity and carcinogenicity assays. however the genotoxic mechanism of entecavir remains elusive. to evalu ...201626800464
aic649 induces a bi-phasic treatment response in the woodchuck model of chronic hepatitis b.aic649 has been shown to directly address the antigen presenting cell arm of the host immune defense leading to a regulated cytokine release and activation of t cell responses. in the present study we analyzed the antiviral efficacy of aic649 as well as its potential to induce functional cure in animal models for chronic hepatitis b. hepatitis b virus transgenic mice and chronically woodchuck hepatitis virus (whv) infected woodchucks were treated with aic649, respectively. in the mouse system ai ...201526656974
property of hepatitis b virus replication in tupaia belangeri hepatocytes.the northern treeshrew (tupaia belangeri) has been reported to be an effective candidate for animal infection model with hepatitis b virus (hbv). the objective of our study was to analyze the growth characteristics of hbv in tupaia hepatocytes and the host response to hbv infection. we established primary tupaia hepatocytes (3-6-week old tupaia) and infected them with hbv genotypes a, b and c, and all the genotypes proliferated as well as those in human primary hepatocytes (>10(5) copies/ml in c ...201626654952
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
combination therapy including cpg oligodeoxynucleotides and entecavir induces early viral response and enhanced inhibition of viral replication in a woodchuck model of chronic hepadnaviral infection.cpg oligodeoxynucleotides (odns) stimulate immune cells via tlr9 and are potentially useful immunomodulators for the treatment of chronic viral infections. in the present study, different classes of cpgs were tested for their capacities for innate immune activation and antiviral activities in the woodchuck model. a class p cpg odn was found to stimulate interferon (ifn) production in woodchuck peripheral blood mononuclear cells (pbmcs) in vitro, and following subcutaneous administration in vivo, ...201626585244
xrcc1 rs25487 genetic variant and tp53 mutation at codon 249 predict clinical outcomes of hepatitis b virus-related hepatocellular carcinoma after hepatectomy: a cohort study for 10 years' follow up.to investigate the effects of rs25487 (the dna repair gene: x-ray repair complementing defective repair in chinese hamster cells 1 [xrcc1]) and codon 249 mutation (tp53 gene) on clinical outcomes of post-hepatectomy hepatitis b virus (hbv)-related hcc.201626519348
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
antibody response to revaccination among adult non-responders to primary hepatitis b vaccination in china.about 10% adult failed to develop antibody response after primary hepatitis b vaccination, and revaccination may be an option to improve immune response, but the antibody responses to revaccination in adult non-responders have not been fully examined. adult non-responders to primary 3-dose hepatitis b vaccination were randomly divided into 2 groups and revaccinated with 20 μg hepatitis b vaccine (hepb) derived from saccharomyces cerevisiae (hepb-sc) or 20 μg hepb derived from chinese hamster ova ...201526252481
a novel linear neutralizing epitope of hepatitis e virus.hepatitis e virus (hev) is a serious public health problem that causes acute hepatitis in humans and is primarily transmitted through fecal and oral routes. the major anti-hev antibody responses are against conformational epitopes located in a.a. 459-606 of hev porf2. all reported neutralization epitopes are present on the dimer domain constructed by this peptide. while looking for a neutralizing monoclonal antibody (mab)-recognized linear epitope, we found a novel neutralizing linear epitope (l ...201526051517
the chimpanzee model for hepatitis b virus infection.even before the discovery of hepatitis b virus (hbv), it was known that chimpanzees (pan troglodytes) are susceptible to human hepatitis viruses. the chimpanzee is the only primate animal model for hbv infections. much like hbv-infected human patients, chimpanzees can develop acute and chronic hbv infections and consequent hepatitis. chimpanzees also develop a cellular immune response similar to that observed in humans. for these reasons, the chimpanzee has proven to be an invaluable model for i ...201526033082
persistence of the recombinant genomes of woodchuck hepatitis virus in the mouse model.hydrodynamic injection (hi) with a replication competent hepatitis b virus (hbv) genome may lead to transient or prolonged hbv replication in mice. however, the prolonged hbv persistence after hi depends on the specific backbone of the vector carrying hbv genome and the genetic background of the mouse strain. we asked whether a genetically closely related hepadnavirus, woodchuck hepatitis virus (whv), may maintain the gene expression and replication in the mouse liver after hi. interestingly, we ...201525942393
a human monoclonal antibody against hepatitis b surface antigen with potent neutralizing activity.we describe the production and characterization of human monoclonal antibodies (mab) specific for the major hepatitis b virus (hbv) s protein. the mabs, two igg1κ and one igg1λ, were secreted by b-cell clones obtained from peripheral blood mononuclear cells (pbmc) of one person convalescent from acute hepatitis b and one vaccinated individual. the former recognized a denaturation-insensitive epitope within the p24 protein whereas the latter recognized a denaturation-sensitive, conformational epi ...201525923526
chronic hepatitis b virus infection and occurrence of hepatocellular carcinoma in tree shrews (tupaia belangeri chinensis).hepatitis b virus (hbv) infection has been believed as a major cause of hepatocellular carcinoma (hcc) for a long time, however, the evidences of which are mostly from clinical and epidemiological investigations while there is no evidence from animal experiments. tree shrew (tupaia) is a small animal closely related to primates evolutionarily, with about 8 years of lifespan. our previous study proved that tree shrews can be chronically hbv-infected after being inoculated neonatally with hbv. the ...201525889678
animal models and the molecular biology of hepadnavirus infection.australian antigen, the envelope protein of hepatitis b virus (hbv), was discovered in 1967 as a prevalent serum antigen in hepatitis b patients. early electron microscopy (em) studies showed that this antigen was present in 22-nm particles in patient sera, which were believed to be incomplete virus. complete virus, much less abundant than the 22-nm particles, was finally visualized in 1970. hbv was soon found to infect chimpanzees, gorillas, orangutans, gibbon apes, and, more recently, tree shr ...201525833941
serological and molecular evidence of hepadnavirus infection in swine.recently, investigations in a swine herd identified evidence of the existence of a novel member of the hepadnavirus family endemic in swine. the aim of this study was to investigate the serological and molecular markers of hepadnavirus circulation in brazilian domestic swine and wild boar herds, and to evaluate the identity with hbv and other hepadnaviruses reported previously.201525780820
liver-directed gene therapy of chronic hepadnavirus infection using interferon alpha tethered to apolipoprotein a-i.current hepatitis b virus (hbv) management is challenging as treatment with nucleos(t)ide analogues needs to be maintained indefinitely and because interferon (ifn)-α therapy is associated with considerable toxicity. previously, we showed that linking ifnα to apolipoprotein a-i generates a molecule (ia) with distinct antiviral and immunostimulatory activities which lacks the hematological toxicity of ifnα.201525772035
primate immune responses to hiv-1 env formulated in the saponin-based adjuvant abisco-100 in the presence or absence of tlr9 co-stimulation.protein-based vaccines require adjuvants to achieve optimal responses. toll-like receptor (tlr) 9 agonists were previously shown to improve responses to protein-based vaccines, such as the hepatitis b virus vaccine formulated in alum. here, we used cpg-c together with the clinically relevant saponin-based adjuvant abisco-100/matrix-m (abisco), to assess if tlr9 co-stimulation would quantitatively or qualitatively modulate hiv-1 envelope glycoprotein (env)-specific b and t cell responses in rhesu ...201525762407
obtaining chicken primordial germ cells used for gene transfer: in vitro and in vivo results.recently, several attempts have been made to create a generation of transgenic chickens via chimeric intermediates produced by primordial germ cells (pgcs) transfer. this study aimed to compare the influences of different chicken pgcs isolated from circulating blood (bpgcs) or gonads (gpgcs), purification (ack, percoll or trypsin) and transfection methods (electroporation or lipofection) on the expression of transgenes in vitro and the migration of modified donor cells to the recipient gonads. t ...201525737138
the one year effects of three doses of hepatitis b vaccine as a booster in anti-hbs-negative children 11-15 years after primary immunization; china, 2009-2011.the aim of this study was to evaluate hepatitis b surface antibody (anti-hbs) levels one year after hepatitis b booster vaccination in anti-hbs-negative (<10 miu/ml) children 11-15 y after primary vaccination. anti-hbs titers were examined in 235 children who were negative for hepatitis b surface antigen (hbsag), anti-hbs, and hepatitis b core antibody (anti-hbc). the children were then divided into 3 groups based on their anti-hbs levels pre-booster: group i, <0 .1 miu/ml; group ii, 0.1 to <1 . ...201525692413
animal models of chronic hepatitis delta virus infection host-virus immunologic interactions.hepatitis delta virus (hdv) is a defective rna virus that has an absolute requirement for a virus belonging to the hepadnaviridae family like hepatitis b virus (hbv) for its replication and formation of new virions. hdv infection is usually associated with a worsening of hbv-induced liver pathogenesis, which leads to more frequent cirrhosis, increased risk of hepatocellular carcinoma (hcc), and fulminant hepatitis. importantly, no selective therapies are available for hdv infection. the mainstay ...201525686091
woodchuck hepatitis virus core gene deletions and proliferative responses of peripheral blood mononuclear cells stimulated by an immunodominant epitope: a viral immune escape in the woodchuck model of chronic hepatitis b?marmota monax and its natural infection by woodchuck hepatitis virus (whv) could be used as a predictive model for evaluating mechanisms of viral persistence during chronic hepatitis b virus (hbv) infection. the aim of this study was to investigate the presence of viral variants in the core gene of chronically whv-infected woodchucks that showed two different patterns of peripheral blood mononuclear cells' (pbmcs') responses after stimulation with a specific whv core peptide. sequences' analysis ...201525666197
[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
therapeutic vaccines in hbv: lessons from hcv.currently, millions of people infected with hepatitis b virus (hbv) are committed to decades of treatment with anti-viral therapy to control viral replication. however, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. this has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing hbeag seroconversion--an end-point that has been associated with a decrease in the rates of ...201525573348
sustained efficacy and seroconversion with the toll-like receptor 7 agonist gs-9620 in the woodchuck model of chronic hepatitis b.new therapies for chronic hepatitis b (chb) are urgently needed since current treatments rarely lead to cure. we evaluated whether the oral small molecule toll-like receptor (tlr7) agonist gs-9620 could induce durable antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus (whv), a hepadnavirus closely related to human hepatitis b virus (hbv).201525559326
therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis b: preclinical studies in the woodchuck.infection with hepatitis b virus (hbv) may lead to subclinical, acute or chronic hepatitis. in the prevaccination era, hbv infections were endemic due to frequent mother to child transmission in large regions of the world. however, there are still estimated 240 million chronic hbv carriers today and ca. 620,000 patients die per year due to hbv-related liver diseases. recommended treatment of chronic hepatitis b with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory result ...201525535101
woodchuck hepatitis virus core antigen-based dna and protein vaccines induce qualitatively different immune responses that affect t cell recall responses and antiviral effects.t helper type 1 (th1) immunity was considered to play a dominant role in viral clearance of hepadnaviral infection. however, pre-primed th2 type responses were able to efficiently control hepadnaviral infection in animal models. we investigated how pre-primed th1/2 responses control hepadnaviral replication using the newly established mouse models. dna (pwhcim, pctla-4-c) and protein vaccines based on the nucleocapsid protein (whcag) of woodchuck hepatitis virus (whv) primed specific immune resp ...201525462346
the long-term efficacy of chinese hamster ovary cell derived hepatitis b vaccine after being used for 14-16 years in chinese rural communities.to evaluate the long-term efficacy of chinese hamster ovary (cho) cell derived hepatitis b vaccine after being used for 14-16 years in country community in hebei province in china.201525454089
superinfection with woodchuck hepatitis virus strain whvny of livers chronically infected with strain whv7.the determinants of the maintenance of chronic hepadnaviral infection are yet to be fully understood. a long-standing unresolved argument in the hepatitis b virus (hbv) research field suggests that during chronic hepadnaviral infection, cell-to-cell spread of hepadnavirus is at least very inefficient (if it occurs at all), virus superinfection is an unlikely event, and chronic hepadnavirus infection can be maintained exclusively via division of infected hepatocytes in the absence of virus spread ...201525320318
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
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
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
Displaying items 801 - 900 of 1060