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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
pathology in practice. b virus infection in a rhesus macaque. 201323600779
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
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
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
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
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
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
[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
[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
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
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
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
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
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
the woodchuck hepatitis b virus infection model for the evaluation of hbv therapies and vaccine therapies.studies focused on the understanding of the molecular mechanisms involved in recovery or progression to chronicity of hbv may take advantage of natural and experimental models that mimic its properties. this is also of relevance for associated diseases such as cirrhosis and hepatocellulocarcinoma. the eastern woodchuck (marmota monax) infected by the hepadnavirus woodchuck hepatitis b virus (whv) has been applied as a predictive model to support development of new hbv vaccines, antivirals, immun ...201022822718
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
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
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
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
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
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
efficient and inducible production of human interleukin 6 in chinese hamster ovary cells using a novel expression system.high level and inducible production of human interleukin 6 (hil-6) was achieved using a novel expression system in chinese hamster ovary (cho) cells. in this system, the transcription of hil-6 gene under the control of phcmv*-1 promoter composed of tetracycline operator sequences and a minimal promoter is activated by a chimeric transactivator (tta) composed of tetracycline repressor and transactivating domain of vp16 protein of herpes simplex virus. the transcription of tta gene, which is also ...199722358879
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
dna immunization with fusion of ctla-4 to hepatitis b virus (hbv) core protein enhanced th2 type responses and cleared hbv with an accelerated kinetic.typically, dna immunization via the intramuscular route induces specific, th1-dominant immune responses. however, plasmids expressing viral proteins fused to cytotoxic t lymphocyte antigen 4 (ctla-4) primed th2-biased responses and were able to induced effective protection against viral challenge in the woodchuck model. thus, we addressed the question in the mouse model how the th1/th2 bias of primed immune responses by a dna vaccine influences hepatitis b virus (hbv) clearance.201121799884
surface antibody and cytokine response to recombinant chinese hamster ovary cell (cho) hepatitis b vaccine.to compare the immune responses of the 10++g and 20++g doses of cho hepatitis b vaccine on adults.201121722684
are endogenous feline leukemia viruses really endogenous?full length endogenous feline leukemia virus (felv) proviruses exist within the genomes of many breeds of domestic cat raising the possibility that they may also exist in a transmissible exogenous form. such viruses would share receptor usage with the recombinant felv-b subgroup, a viral subgroup that arises in vivo by recombination between exogenous subgroup a virus (felv-a) and endogenous felv. accordingly, all isolates of felv-b made to date have contained a "helper" felv-a, consistent with t ...201121715022
suppression of hepatitis b virus replication in tupaia hepatocytes by tumor necrosis factor alpha of tupaia belangeri.recently, tupaia belangeri was used to study the full replication cycle of hepatitis b virus (hbv) in the primary hepatocyte cultures. thus, the tupaia model represents a suitable model to study the effects of cytokines on hbv infection. here, tupaia tumor necrosis factor-alpha (tnf-+¦) was molecularly cloned and expressed in mammalian cells. a test system for the biological activity of tupaia tnf-+¦ was established on the basis of its cytotoxic effect to the murine fibrosarcoma cell line l929. ...201121684599
evaluation of a novel non-penetrating electrode for use in dna vaccination.current progress in the development of vaccines has decreased the incidence of fatal and non-fatal infections and increased longevity. however, new technologies need to be developed to combat an emerging generation of infectious diseases. dna vaccination has been demonstrated to have great potential for use with a wide variety of diseases. alone, this technology does not generate a significant immune response for vaccination, but combined with delivery by electroporation (ep), can enhance plasmi ...201121559474
detection of viruses in used ventilation filters from two large public buildings.background: viral and bacterial pathogens may be present in the air after being released from infected individuals and animals. filters are installed in the heating, ventilation, and air-conditioning (hvac) systems of buildings to protect ventilation equipment and maintain healthy indoor air quality. these filters process enormous volumes of air. this study was undertaken to determine the utility of sampling used ventilation filters to assess the types and concentrations of virus aerosols presen ...201121549446
avian metapneumovirus subtypes circulating in brazilian vaccinated and nonvaccinated chicken and turkey farms.avian metapneumovirus (ampv) causes turkey rhinotracheitis and is associated with swollen head syndrome in chickens, which is usually accompanied by secondary infections that increase mortality. ampvs circulating in brazilian vaccinated and nonvaccinated commercial chicken and turkey farms were detected using a universal reverse transcriptase (rt)-pcr assay that can detect the four recognized subtypes of ampv. the ampv status of 228 farms with respiratory and reproductive disturbances was invest ...201121500641
electroporation enhances immunogenicity of a dna vaccine expressing woodchuck hepatitis virus surface antigen in woodchucks.the development of therapeutic vaccines for chronic hepatitis b virus (hbv) infection has been hampered by host immune tolerance and the generally low magnitude and inconsistent immune responses to conventional vaccines and proposed new delivery methods. electroporation (ep) for plasmid dna (pdna) vaccine delivery has demonstrated the enhanced immunogenicity of hbv antigens in various animal models. in the present study, the efficiency of the ep-based delivery of pdna expressing various reporter ...201121389124
ulcerative cheilitis in a rhesus macaque.a 2-year-old, female, simian immunodeficiency virus e543-infected rhesus macaque (macaca mulatta) was presented for necropsy following euthanasia due to a history of diarrhea, weight loss, and a small, round ulcer along the left labial commissure. histopathologic examination of the ulcer revealed infiltration by large numbers of degenerate and nondegenerate neutrophils and macrophages admixed with syncytial epithelial cells. rare epithelial cells contained herpetic inclusion bodies. these cells ...201121383117
debilitating clinical disease in a wild-born captive western lowland gorilla (gorilla gorilla gorilla) co-infected with varicella zoster virus (vzv) and simian t-lymphotropic virus (stlv).a wild-born, 34-yr-old female western lowland gorilla (gorilla gorilla gorilla) was transferred between zoologic collections in the united kingdom. adjustment to its new environment was difficult and a series of health problems ensued. progressive severe illness of multiple etiologies, and a failure to respond to multiple therapies, led to its euthanasia 5 mo later. disease processes included severe thoracic and axillary cutaneous ulceration of t2-3 dermatome distribution, gastroenteritis, ulcer ...201021370655
[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
[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
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
[study on the immuno-effects and influencing factors of chinese hamster ovary (cho) cell hepatitis b vaccine among adults, under different dosages.]objective: to evaluate the immuno-effect and related influencing factors on 10 µg and 20 µg chinese hamster ovary (cho) cell hepatitis b vaccine, using the randomized double-blind controlled trials in adult population. methods: a total of 642 adults aged 18 - 45 years old, non-vaccinated against hepatitis b, and negative on five blood indicators for hepatitis b, were selected as the study objects from four districts in beijing. the study objects were randomly divided into two groups, and then ac ...201021162840
establishing a new animal model for hepadnaviral infection: susceptibility of chinese marmota-species to woodchuck hepatitis virus infection.hepatitis b virus infection (hbv) is a major medical problem in china. the lack of a suitable infection model in china is recognized as an obstacle for research on hbv in china. chinese marmota-species is phylogenetically closely related to marmota monax, thus, it might be suitable to serve as an animal model for hbv infection. therefore, we attempted to prove the claim about the existence of woodchuck hepatitis virus (whv)-like viruses in chinese marmota-species and to determine the susceptibil ...201021084496
the "original" hepatitis b virus of eastern chimpanzees (pan trogrodytes schweinfurthii).little is known about hepatitis b virus (hbv) infections in chimpanzees. therefore, we investigated the prevalence of chimpanzee hbv (chhbv) infections in captive, wild born chimpanzees in the sanctuary on ngamba island, uganda and one sample from a wild free ranging chimpanzee. in one third of the plasma samples (32.4%; 12/37) we detected antibodies to hepatitis b (core) antigen. amongst those individuals hbv dna was detected in one captive wild born and the wild chimpanzee. in contrast to the ...201020970465
the c-terminal region of the hepatitis b virus x protein is essential for its stability and function.more than 350 million people worldwide are chronically infected with the human hepatitis b virus (hbv). chronic hbv infections are associated with the development of hepatocellular carcinoma. while the mechanism of hbv-associated carcinoma remains undefined, it is thought to involve a combination of a continuous inflammatory response to hbv-infected hepatocytes and activities of hbv proteins such as the hbv x protein (hbx). hbx stimulates hbv replication; however, the mechanism by which hbx stim ...201020969903
screening of a high growth influenza b virus strain in vero cells.due to the insufficient supply of embryonated chicken eggs, the preparation of large quantities of inactivated influenza vaccines will require an alternative virus culture system after the emergence or reemergence of a pandemic influenza virus. the vero cell is one of the ideal options since it was used for producing many kinds of human vaccines. however, most of the influenza viruses can not grow well in vero cells. to develop a new influenza vaccine with vero cells as a substrate, the virus ne ...201020960286
establishment of a cynomolgus macaque model of influenza b virus infection.pathogenicity of influenza b virus was examined in cynomolgus macaques to establish a macaque model suitable for vaccine and antiviral drug development. we prepared influenza b viruses for inoculation with minimal passages after isolation from patients. macaques inoculated with influenza b virus showed higher body temperature than that before infection for 6 to 12 days. virus was detected in nasal, tracheal, and bronchial samples until 6 days after inoculation followed by an increase in neutrali ...201020822788
identification of cd4+ and cd8+ t cell epitopes of woodchuck hepatitis virus core and surface antigens in balb/c mice.a therapeutic vaccine against chronic hepatitis b virus (hbv) infection requires the development of a strong and multispecific th1 cell immune response. woodchucks chronically infected with the woodchuck hepatitis virus (whv) closely resemble hbv infection and represent the best animal model for this hepadnavirus-induced disease. using the bimas "hla peptide binding predictions" program, we have identified and further characterized novel h-2 d-restricted cd8+ epitopes within the whv core (peptid ...201020665977
glucosidase inhibition enhances presentation of de-n-glycosylated hepatitis b virus epitopes by major histocompatibility complex class i in vitro and in woodchucks.in this report, the possibility of pharmacologically altering the hepatitis b virus (hbv) epitopes presented by major histocompatibility complex class i on infected cells is demonstrated. the hbv middle envelope glycoprotein (mhbs) maturation appears to require calnexin-mediated folding. this interaction is dependent on glucosidases in the endoplasmic reticulum. prevention of hbv envelope protein maturation in cultured cells through use of glucosidase inhibitors, such as 6-o-butanoyl castanosper ...201020658465
the woodchuck: a model for therapeutic vaccination against hepadnaviral infection.interferon-alpha and nucleoside analogues are available for the treatment of chronic hepatitis b virus (hbv) infection but do not lead to a satisfactory result. new findings about the immunological control of hbv during acute infection suggest the pivotal role of t-cell mediated immune responses. several preclinical and clinical trials were undertaken to explore the possibility of stimulating specific immune responses in chronically infected animals and patients by vaccination. however, vaccinat ...201020646874
experimental helicobacter marmotae infection in a/j mice causes enterohepatic disease.helicobacter marmotae has been identified in the inflamed livers of eastern woodchucks (marmota monax) infected with woodchuck hepatitis virus (whv), as well as from the livers of whv-negative woodchucks. because the majority of whv-positive woodchucks with hepatic tumours were culture or pcr positive for this helicobacter, and whv-negative woodchucks with h. marmotae had hepatitis, the bacterium may have a role in tumour promotion related to chronic inflammation. in this study, the type strain ...201020616187
apobec1 and apobec3 cytidine deaminases as restriction factors for hepadnaviral genomes in non-humans in vivo.reverse transcription of the hepadnavirus rna pre-genome means that nascent cdna may be vulnerable to genetic editing by host cell apobec cytidine deaminases that have specificity single-stranded dna as substrate. hepatitis b virus (hbv) is particularly vulnerable to editing by apobec3g (ha3g) in late-stage disease where up to 35% of genomes can be edited. yet, the organization of the a3 locus varies considerably among mammals with a single gene for the mouse and seven genes for old and new worl ...201020546753
proteomic analysis of primary duck hepatocytes infected with duck hepatitis b virus.abstract:201020529248
detection and characterization of clade 7 high pathogenicity avian influenza h5n1 viruses in chickens seized at ports of entry and live poultry markets in vietnam.high pathogenicity avian influenza h5n1 has become an endemic poultry disease in several asian countries, including vietnam. recently, dade 7 h5n1 viruses of the eurasian lineage were isolated from chickens seized at ports of entry in lang son province, vietnam. extensive nucleotide and amino acid divergence across the hemagglutinin (ha) protein gene of these isolates in comparison to previously described clade 7 viruses was identified. clade 7 viruses are antigenically distinct from contemporar ...201020521651
clonal expansion of normal-appearing human hepatocytes during chronic hepatitis b virus infection.chronic hepatitis b virus (hbv) infections are associated with persistent immune killing of infected hepatocytes. hepatocytes constitute a largely self-renewing population. thus, immune killing may exert selective pressure on the population, leading it to evolve in order to survive. a gradual course of hepatocyte evolution toward an hbv-resistant state is suggested by the substantial decline in the fraction of infected hepatocytes that occurs during the course of chronic infections. consistent w ...201020519397
establishment of specific pathogen-free macaque colonies in tsukuba primate research center of japan for aids research.cynomolgus monkeys have been maintained in indoor facilities as closed colony monkeys in tsukuba primate research center in japan since 1978. several microorganisms, including bacteria, parasites and viruses, were eliminated from the cynomolgus monkeys in this colony of tprc. various kinds of viruses (b virus, measles virus, simian varicella virus, simian immunodeficiency virus, simian t cell leukemia virus, simian d type retrovirus, simian cytomegalovirus, simian epstein-barr virus, and simian ...201020510748
establishment and characterization of a madin-darby canine kidney reporter cell line for influenza a virus assays.influenza virus diagnosis has traditionally relied on virus isolation in chicken embryo or cell cultures. many laboratories have adopted rapid molecular methods for detection of influenza viruses and discontinued routine utilization of the relatively slow viral culture methods. we describe an influenza a virus reporter cell line that contributes to more efficient viral detection in cell culture. madin-darby canine kidney (mdck) cells were engineered to constitutively produce an influenza virus g ...201020504984
detection and characterization of hepatitis b virus strains from wild-caught gorillas and chimpanzees in cameroon, central africa.previous epidemiological studies have reported a high prevalence of hepatitis b virus (hbv) infection in chimpanzees in gabon and congo, central africa. there is no data for this species from cameroon. to date few cases of active hbv infection have been documented in gorillas and only one complete hbv sequence has been described from a wild-caught gorilla originating from cameroon and housed in germany. since gorillas are apes found in cameroon, we thus investigated the prevalence and genetic re ...201020471498
pre-acute hepadnaviral infection is associated with activation-induced apoptotic death of lymphocytes in the woodchuck (marmota monax) model of hepatitis b.woodchucks (marmota monax) infected with woodchuck hepatitis virus (whv) represent a highly valuable immunopathogenic model of hepatitis b virus (hbv) infection. both whv and hbv are noncytopathic hepadnaviruses which induce a strong but delayed virus-specific cellular immune response believed to be a cause of hepatitis. the reason behind this postponement is not well understood and its dissection in the woodchuck model has been hampered by the lack of appropriate research tools. in this study, ...201020451550
[impact of different adjuvants on immunogenicity of the hbv particle vaccine containing the s + pres1 fusion antigen in balb/c mice].we previous reported the development of novel hepatitis b virus(hbv) vaccine containing the surface antigen(s) plus pres1 fusion derived from chinese hamster ovary (cho) cells system. in this study, we analyzed the impact of different adjuvants on immunogenicity of the hbv particle vaccine in balb/c mice, including alum alone, cpg oligodeoxynucleotides (cpg-odn) alone and cpg-odn in combination with alum adjuvant. we first detected the antigen specific humoral response in mice, including total i ...201020353095
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
cercopithecine herpesvirus 1 risk in a child bitten by a bonnet macaque monkey.background: exotic animal importation and trade has the potential to expose the public to a variety of injuries and diseases not endemic to the united states. bonnet macaque monkeys are a fairly common primate illegally held in captivity. these monkeys become aggressive as they age past 2 years and are known to carry asymptomatic cercopithecine herpesvirus 1 infection. objective: this case is presented to illustrate the point that simple wound management alone may not only be insufficient but co ...201020347250
detection of avian metapneumovirus subtypes in turkeys using rt-pcr.this study investigated the prevalence of avian metapneumovirus (ampv) and the detection of molecular subtypes of field strains of the virus using rt-pcr in clinically healthy turkeys and those showing signs of respiratory disease. in the rt-pcr examination of 624 tracheal tissue samples collected from a local turkey abattoir, 2.9 per cent (18/624) of samples tested positive. in the examination of tracheal swab samples collected from flocks with respiratory problems, 18 of 20 samples tested posi ...201020305292
hepatitis b virus replication in primary macaque hepatocytes: crossing the species barrier toward a new small primate model.the development of new anti-hepatitis b virus (hbv) therapies, especially immunotherapeutic approaches, has been limited by the lack of a primate model more accessible than chimpanzees. we have previously demonstrated that sylvanus and cynomolgus macaques are susceptible to in vivo hbv infection after intrahepatic hbv dna inoculation. in this study, we evaluated the susceptibility of primary macaque hepatocytes (pmhs) to hbv infection with a highly efficient hbv genome-mediated transfer system v ...201020301206
hbx protein is indispensable for development of viraemia in human hepatocyte chimeric mice.the non-structural x protein, hbx, of hepatitis b virus (hbv) is assumed to play an important role in hbv replication. woodchuck hepatitis virus x protein is indispensable for virus replication, but the duck hepatitis b virus x protein is not. in this study, we investigated whether the hbx protein is indispensable for hbv replication in vivo using human hepatocyte chimeric mice. hbx-deficient (hbx-def) hbv was generated in hepg2 cells by transfection with an overlength hbv genome. human hepatocy ...201020219897
antiviral properties, metabolism, and pharmacokinetics of a novel azolo-1,2,4-triazine-derived inhibitor of influenza a and b virus replication.influenza viruses of types a and b cause periodic pandemics in the human population. the antiviral drugs approved to combat influenza virus infections are currently limited. we have investigated an effective novel inhibitor of human influenza a and b viruses, triazavirine [2-methylthio-6-nitro-1,2,4-triazolo[5,1-c]-1,2,4-triazine-7(4i)-one] (tzv). tzv suppressed the replication of influenza virus in cell culture and in chicken chorioallantoic membranes, and it protected mice from death caused by ...201020194696
initiation of duck hepatitis b virus infection requires cleavage by a furin-like protease.the entry mechanism of hepatitis b virus (hbv) has not been defined, and this impedes development of antiviral therapies aimed at an early step in the viral life cycle. hbv infection has both host and tissue specificities. for the related duck hepatitis b virus (dhbv), duck carboxypeptidase d (dcpd) has been proposed as the species-specific docking receptor, while glycine decarboxylase (dgd) may serve as a tissue-specific cofactor or secondary receptor. dgd binds to several truncated versions of ...201020181690
ethnic-specific prevalence of hepatitis b/c virus infection in pin-jen, taiwan.the study aimed to estimate prevalence rate of hepatitis b/c virus infection by three ethnic groups including hakka, minnan, and mainlander in taiwan where there was a high incidence of hepatocellular carcinoma.200920073137
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