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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
development of high-yield influenza b virus vaccine viruses.the burden of human infections with influenza a and b viruses is substantial, and the impact of influenza b virus infections can exceed that of influenza a virus infections in some seasons. over the past few decades, viruses of two influenza b virus lineages (victoria and yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the world health organization. influenza b virus vaccines for humans have been available for more than half a c ...201627930325
recombinant production and characterization of human anti-influenza virus monoclonal antibodies identified from hybridomas fused with human lymphocytes.in previous studies, hybridomas producing human immunoglobulin g, the antibodies 5e4 and 5a7 against influenza a and b virus were established using a novel human lymphocyte fusion partner, spymeg. in the present study, we succeeded in achieving the recombinant production and secretion of 5e4 and 5a7 in chinese hamster ovary cells. our n-glycan analysis by intact-mass detection and liquid chromatography mass spectrometry showed that recombinant 5e4 and 5a7 have one n-glycan and the typical mammal ...201627464991
rationally designed influenza virus vaccines that are antigenically stable during growth in eggs.influenza virus vaccine production is currently limited by the ability to grow circulating human strains in chicken eggs or in cell culture. to facilitate cost-effective growth, vaccine strains are serially passaged under production conditions, which frequently results in mutations of the major antigenic protein, the viral hemagglutinin (ha). human vaccination with an antigenically drifted strain is known to contribute to poor vaccine efficacy. to address this problem, we developed a replication ...201728588131
marburg virus-like particles produced in insect cells induce neutralizing antibodies in rhesus macaques.marburg virus (marv), which is one of the most virulent agents in the world, causes lethal haemorrhagic fever in humans and nonhuman primates (nhps) with a mortality rate of up to 90%. currently, there is no effective treatment or approved vaccine for marv for human use to control disease outbreak and spread. virus-like particles (vlps), which are morphologically identical to the native infectious virus particle, are efficacious as vaccines against many viruses, including human papilloma virus ( ...201728402024
genome sequence variation among isolates of monkey b virus (macacine alphaherpesvirus 1) from captive macaques.complete genome sequences of 19 strains of monkey b virus (macacine alphaherpesvirus 1; bv) isolated from several macaque species were determined. a low level of sequence variation was present among bv isolates from rhesus macaques. most variation among bv strains isolated from rhesus macaques was located in regions of repetitive or quasi-repetitive sequence. variation in coding sequences (polypeptides and mirnas) was minor compared to regions of non-coding sequences. non-coding sequences in the ...201728494342
interferon-β response is impaired by hepatitis b virus infection in tupaia belangeri.to date, the chimpanzee has been used as the natural infection model for hepatitis b virus (hbv). however, as this model is very costly and difficult to use because of ethical and animal welfare issues, we aimed to establish the tupaia (tupaia belangeri) as a new model for hbv infection and characterized its intrahepatic innate immune response upon hbv infection. first, we compared the propagation of hbv genotypes a2 and c in vivo in tupaia hepatocytes. at 8-10days post infection (dpi), the leve ...201728551415
construction of a hepatitis b virus neutralizing chimeric monoclonal antibody recognizing escape mutants of the viral surface antigen (hbsag).hepatitis b virus (hbv) infection is a global burden on the health-care system and is considered as the tenth leading cause of death in the world. over 248 million patients are currently suffering from chronic hbv infection worldwide and annual mortality rate of this infection is 686000. the "a" determinant is a hydrophilic region present in all antigenic subtypes of hepatitis b surface antigen (hbsag), and antibodies against this region can neutralize the virus and are protective against all su ...201728641998
biological effects of bone marrow mesenchymal stem cells on hepatitis b virus in vitro.the aim of the present study was to explore the effects of co‑culturing bone marrow‑derived mesenchymal stem cells (bm-mscs) cultured with hepatitis b virus (hbv)‑infected lymphocytes in vitro. bm‑mscs and lymphocytes from brown norway rats were obtained from the bone marrow and spleen, respectively. rats were divided into the following five experimental groups: group 1, splenic lymphocytes (slcs); group 2, hepg2.2.15 cells; group 3, bm‑mscs + hepg2.2.15 cells; group 4, slcs + hepg2.2.15 cells; ...201728447750
initial sites of hepadnavirus integration into host genome in human hepatocytes and in the woodchuck model of hepatitis b-associated hepatocellular carcinoma.hepatitis b virus (hbv) and the closely related woodchuck hepatitis virus (whv) are potent carcinogens that trigger development of primary hepatocellular carcinoma (hcc). the initial sites of hepadnavirus-host genome integration, their diversity and kinetics of formation can be central to virus persistence and the initiation and progression of hcc. to recognize the nature of the very early virus-host interactions, we explored de novo infection of human hepatocyte-like heparg cells with authentic ...201728414318
is it possible to develop cancer vaccines to neoantigens, what are the major challenges, and how can these be overcome? neoantigens: nothing new in spite of the name.the term "neoantigen," as applied to molecules newly expressed on tumor cells, has a long history. the groundbreaking discovery of a cancer causing virus in chickens by rous over 100 years ago, followed by discoveries of other tumor-causing viruses in animals, suggested a viral etiology of human cancers. the search for other oncogenic viruses in the 1960s and 1970s resulted in the discoveries of epstein-barr virus (ebv), hepatitis b virus (hbv), and human papilloma virus (hpv), and continues unt ...201729254980
toll-like receptor 7 agonist gs-9620 induces prolonged inhibition of hbv via a type i interferon-dependent mechanism.gs-9620, an oral agonist of toll-like receptor 7 (tlr7), is in clinical development for the treatment of chronic hepatitis b (chb). gs-9620 was previously shown to induce prolonged suppression of serum viral dna and antigens in the woodchuck and chimpanzee models of chb. here we investigated the molecular mechanisms that contribute to the antiviral response to gs-9620 using in vitro models of hepatitis b virus (hbv) infection.201729247725
anti-hbv response to toll-like receptor 7 agonist gs-9620 is associated with intrahepatic aggregates of t cells and b cells.gs-9620, an oral agonist of toll-like receptor 7 (tlr7), is in clinical development for the treatment of chronic hepatitis b (chb). gs-9620 was previously shown to induced prolonged suppression of serum viral dna and antigens in the chimpanzee and woodchuck models of chb. here we investigated the immunomodulatory mechanisms underlying these antiviral effects.201729247724
herpes b virus replication and viral lesions in the liver of a cynomolgus macaque which died from severe disease with rapid onset.herpes b virus (bv, macacine alphaherpesvirus 1) infects macaques asymptomatically, with rare exceptions, but can cause fatal encephalitis in humans. here, we report disseminated bv infection in a cynomolgus macaque that had died within 12 hour after the onset of unspecific symptoms. multifocal lesions surrounded by viral antigen were detected in liver while other organs remained inconspicuous, indicating that the liver is a major target. moreover, high copy numbers of viral dna were found in fe ...201728439900
identification of unique b virus (macacine herpesvirus 1) epitopes of zoonotic and macaque isolates using monoclonal antibodies.our overall aim is to develop epitope-based assays for accurate differential diagnosis of b virus zoonotic infections in humans. antibodies to cross-reacting epitopes on human-simplexviruses continue to confound the interpretation of current assays where abundant antibodies exist from previous infections with hsv types 1 and 2. to find b virus-specific epitopes we cloned ten monoclonal antibodies (mabs) from the hybridomas we produced. our unique collection of rare human sera from symptomatic an ...201728783746
detection systems for antibody responses against herpes b virus.herpes b virus (bv) infection is highly prevalent among adult asian macaques and rarely causes severe disease in infected animals. in contrast, bv infection of humans can induce fatal encephalitis in the absence of treatment. therefore, the development of diagnostic tests for specific and sensitive detection of antibodies against bv is an important task. the cross-reactivity of antibodies against bv with related simplex viruses of other primates may afford an opportunity to obtain sensitive dete ...201732110687
immunization with live human rhinovirus (hrv) 16 induces protection in cotton rats against hrv14 infection.human rhinoviruses (hrvs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against hrvs are available to prevent or mitigate hrv infection. there are more than 150 antigenically heterogeneous hrv serotypes, with ∼90 hrvs belonging to major group species a and b. development of small animal models that are susceptible to infection with major group hrvs would be beneficial for vaccine research. previously, we showed that the cotton rat (sigmodon hispidus) ...201728912760
tumour virus epidemiology.a viral etiology of cancer was first demonstrated in 1911 by peyton rous who injected cell-free filtrate from a chicken sarcoma into healthy chickens and found it induced a tumour. since the discovery over 50 years ago of the epstein-barr virus as the cause of burkitt lymphoma, seven other human viruses or groups of viruses-hepatitis b virus, hepatitis c virus, human immunodeficiency virus type 1, some human papillomaviruses, human t-cell lymphotropic virus type 1, kaposi sarcoma-associated herp ...201728893933
syrian hamster as an animal model for the study of human influenza virus infection.ferrets and mice are frequently used as animal models for influenza research. however, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza a or b viruses. therefore, prior adaptation of human viruses is required for their use in mice. in addition, there are no mouse-adapted variants of the recent h3n2 viruses, because these viruses do not replicate well in mice. in this study, we investigated the susceptibilit ...201729212926
hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis b virus infection of macaques.hepatitis b virus (hbv) is a major global health concern, and the development of curative therapeutics is urgently needed. such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of hbv infection. here, we report that expression of the hbv entry receptor, human sodium-taurocholate cotransporting polypeptide (hntcp), on macaque primary hepatocytes facilitates hbv infection in vitro, where all replicative intermediates including covalently closed circular dna ...201729247188
new avian hepadnavirus in palaeognathous bird, germany.in 2015, we identified an avian hepatitis b virus associated with hepatitis in a group of captive elegant-crested tinamous (eudromia elegans) in germany. the full-length genome of this virus shares <76% sequence identity with other avihepadnaviruses. the virus may therefore be considered a new extant avian hepadnavirus.201729148393
recombinant vaccinia vector-based vaccine (tiantan) boosting a novel hbv subunit vaccine induced more robust and lasting immunity in rhesus macaques.this study explored several prime-boost strategies in rhesus macaques using various novel hepatitis b virus (hbv) vaccines that showed promise as prophylactic and therapeutic approaches in our previous study using in a mouse model. the tested vaccines included an hbv particle subunit (hbss1) vaccine and the recombinant vaccinia (rvjss1) or adenoviral (radss1) vector-based vaccines containing s (1-223aa) and pres1 (21-47aa). the strength and maintenance of humoral activity (igg and neutralizing a ...201728487055
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
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
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
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
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
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
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
safety and efficacy of anti-pd-l1 therapy in the woodchuck model of hbv infection.immune clearance of hepatitis b virus (hbv) is characterized by broad and robust antiviral t cell responses, while virus-specific t cells in chronic hepatitis b (chb) are rare and exhibit immune exhaustion that includes programmed-death-1 (pd-1) expression on virus-specific t cells. thus, an immunotherapy able to expand and activate virus-specific t cells may have therapeutic benefit for chb patients. like hbv-infected patients, woodchucks infected with woodchuck hepatitis virus (whv) can have i ...201829444087
the immune response of rhesus macaques to novel vaccines comprising hepatitis b virus s, pres1, and core antigens.therapeutic vaccines represent a unique approach to hepatitis b virus (hbv) treatment and have the potential to induce long-term control of infection. this study explored the immune responses of rhesus macaques to novel vaccines comprising the s, pres1, and core antigens of the hbv that showed promise as prophylactic and therapeutic approaches in a mouse model. the tested vaccines included two dna vaccines (pvrc-ss1, pvrc-cs1), an hbv particle subunit (hbss1) vaccine and the recombinant vaccinia ...201829778513
hepatitis b vaccination using a dissolvable microneedle patch is immunogenic in mice and rhesus macaques.chronic hepatitis b virus infection remains a major global public health problem, accounting for about 887,000 deaths in 2015. perinatal and early childhood infections are strongly associated with developing chronic hepatitis b. adding a birth dose of the hepatitis b vaccine (hepb bd) to routine childhood vaccination can prevent over 85% of these infections. however, hepb bd coverage remains low in many global regions, with shortages of birth attendants trained to vaccinate and limited hepb bd s ...201830377659
characterisation of the hepatitis b virus cross-species transmission pattern via na+/taurocholate co-transporting polypeptides from 11 new world and old world primate species.the hepatic na+/taurocholate co-transporting polypeptide (ntcp in man, ntcp in animals) is the high-affinity receptor for the hepatitis b (hbv) and hepatitis d (hdv) viruses. species barriers for human hbv/hdv within the order primates were previously attributed to ntcp sequence variations that disable virus-receptor interaction. however, only a limited number of primate ntcps have been analysed so far. in the present study, a total of 11 ntcps from apes, old and new world monkeys were cloned an ...201829912972
animal models for the study of hepatitis b virus infection.even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis b virus (hbv) worldwide. current antiviral therapies, including interferon and nucleot(s)ide analogues, rarely cure chronic hepatitis b. animal models are very crucial for understanding the pathogenesis of chronic hepatitis b and developing new therapeutic drugs or strategies. hbv can only infect humans and chimpanzees, with the use of chimpanzees in hbv research strongly restricted. thus, mos ...201829511142
macacine herpesvirus 1 antibody prevalence and dna shedding among invasive rhesus macaques, silver springs state park, florida, usa.we compiled records on macacine herpesvirus 1 (mchv-1) seroprevalence and, during 2015-2016, collected saliva and fecal samples from the free-ranging rhesus macaques of silver springs state park, a popular public park in central florida, usa, to determine viral dna shedding and perform sequencing. phylogenetic analysis of the us5 and us5-us6 intragenic sequence from free-ranging and laboratory mchv-1 variants did not reveal genomic differences. in animals captured during 2000-2012, average annua ...201829350146
2,4-diaminoquinazolines as dual toll-like receptor (tlr) 7/8 modulators for the treatment of hepatitis b virus.a novel series of 2,4-diaminoquinazolines was identified as potent dual toll-like receptor (tlr) 7 and 8 agonists with reduced off-target activity. the stereochemistry of the amino alcohol was found to influence the tlr7/8 selectivity with the ( r) isomer resulting in selective tlr8 agonism. lead optimization toward a dual agonist afforded ( s)-3-((2-amino-8-fluoroquinazolin-4-yl)amino)hexanol 31 as a potent analog, being structurally different from previously described dual agonists ( mcgowan j ...201829965759
questioning the extreme neurovirulence of monkey b virus (macacine alphaherpesvirus 1).monkey b virus (macacine alphaherpesvirus 1; bv) occurs naturally in macaques of the genus macaca, which includes rhesus and long-tailed (cynomolgus) monkeys that are widely used in biomedical research. bv is closely related to the human herpes simplex viruses (hsv), and bv infections in its natural macaque host are quite similar to hsv infections in humans. zoonotic bv is extremely rare, having been diagnosed in only a handful of north american facilities with the last documented case occurring ...201829666644
tlr7 agonist increases responses of hepatitis b virus-specific t cells and natural killer cells in patients with chronic hepatitis b treated with nucleos(t)ide analogues.the oral toll-like receptor (tlr) 7 agonist gs-9620 has antiviral effects in woodchuck and chimpanzee models of chronic hepatitis b virus (hbv) infection. we investigated, in a clinical trial, the capacity of this agent to reconstitute protective immunity in patients with chronic hbv infection.201829378197
immunogenicity of adenovirus-vector vaccine targeting hepatitis b virus: non-clinical safety assessment in non-human primates.a new promising therapeutic approach has emerged for patients chronically infected by the hepatitis b virus (hbv) with the development of a non-replicative adenovirus vector vaccine candidate (ad-hbv). the vaccine encodes a fusion protein composed of a truncated hbv core protein, mutated polymerase protein, and two envelope domains. in this study, we assessed the immunogenicity of ad-hbv administered to cynomolgus monkeys during a non-clinical safety assessment.201830041659
a novel hepadnavirus identified in an immunocompromised domestic cat in australia.high-throughput transcriptome sequencing allows for the unbiased detection of viruses in host tissues. the application of this technique to immunosuppressed animals facilitates the detection of viruses that might otherwise be excluded or contained in immunocompetent individuals. to identify potential viral pathogens infecting domestic cats we performed high-throughput transcriptome sequencing of tissues from cats infected with feline immunodeficiency virus (fiv). a novel member of the hepadnavir ...201829772771
anti-influenza a viral butenolide from streptomyces sp. smu03 inhabiting the intestine of elephas maximus.actinobacteria are a phylum of bacteria known for their potential in producing structurally diversified natural products that are always associated with a broad range of biological activities. in this paper, using an h5n1 pseudo-typed virus drug screening system combined with a bioassay guided purification approach, an antiviral butanolide (1) was identified from the culture broth of streptomyces sp. smu03, a bacterium isolated from the feces of elephas maximus in yunnan province, china. this co ...201829976861
in vitro anti-hepatitis b virus activity of 2',3'-dideoxyguanosine.2',3'-dideoxyguanosine (dog) has been demonstrated to inhibit duck hepatitis b virus (dhbv) replication in vivo in a duck model of hbv infection. in the current study, the in vitro antiviral effects of dog on human and animal hepadnaviruses were investigated. our results showed that dog effectively inhibited hbv, dhbv, and woodchuck hepatitis virus (whv) replication in hepatocyte-derived cells in a dose-dependent manner, with 50% effective concentrations (ec50) of 0.3 ± 0.05, 6.82 ± 0.25, and 23 ...201830421112
chinese woodchucks with different susceptibility to whv infection differ in their genetic background exemplified by cytochrome b and mhc-drb molecules.chinese woodchucks (m. himalayana) were recently found to be susceptible to woodchuck hepatitis virus (whv) infection. in this study, we aimed to determine the susceptibility to whv infection of m. himalayana from different areas and their association with the animal genetic background exemplified by cytochrome b and mhc-drb molecules.201829914514
differential expression of woodchuck toll-like receptors 1-10 in distinct forms of infection and stages of hepatitis in experimental hepatitis b virus infection.woodchucks infected with woodchuck hepatitis virus (whv) represent a highly valuable model of human hepatitis b virus (hbv) infection, chronic hepatitis (ch), and virus induced-primary liver cancer. toll-like receptors (tlrs) are important mediators of immune responses playing pivotal roles in the pathogenesis of viral diseases; however, their expression profiles in different forms of infection and stages of hepatitis, and in healthy animals remain essentially unknown. in this study, woodchuck t ...201830581424
cross-protective efficacy of monovalent live influenza b vaccines against genetically different lineages of b/victoria and b/yamagata in ferrets.currently, two genetic lineages of influenza b virus, b/victoria and b/yamagata, are cocirculating in humans in various countries. this situation has raised a question regarding the possibility of cross-protection between b components of live attenuated influenza vaccine (laiv) belonging to different lineages. this study aimed to assess in naïve ferrets the potential protective activity of monovalent b-laivs against challenge with homologous and heterologous wild-type (wt) influenza b viruses.201830246028
[swine-spread severe influenza-associated pneumonia: a case report and literature review].we report and analyze the clinical data of the first case of severe pneumonia caused by influenza b virus from swine. the patient, a 62 year-old male domestic pig breeder, was admitted to hospital because of fever and muscle pain for 5 days, and anhelation for 3 days. one week before the onset of disease, the patient kept close contact with pigs. ct scan of the chest showed diffuse infiltration in both lungs. influenza b virus antigen detection (colloidal gold method) was repeatedly positive. th ...201830643075
relationship between environmental factors and the spatial distribution of spermophilus dauricus during 2000-2015 in china.the spermophilus dauricus is a rodent species that feeds on the tender parts of plants and seeds. it is also a natural carrier of the hepatitis b virus and the main host of the plague bacillus yersinia pestis threatening human health and the cultivated ecosystems. based on ecological niche modeling (enm) for the maxent model and arcgis for the spatial analyst model, we quantified the potential risk zone and spatial pattern of the s. dauricus outbreak during 2000-2015. we analyze the temporal and ...201830019314
long-term surveillance of langur alphaherpesvirus in a zoo population of silvered langurs ( trachypithecus cristatus).langur alphaherpesvirus (hvl), a provisionally named alphaherpesvirus in the simplexvirus genus, was first identified in 1991 at the bronx zoo in wild-origin silvered langurs ( trachypithecus cristatus) and their descendants. hvl is closely related to b virus ( macacine alphaherpesvirus 1) based on serologic and genetic data, but its natural history and zoonotic potential remain unknown. a cohort study was undertaken to describe the epidemiology, clinical impact, and potential management implica ...201829900798
experimental infection of racing pigeons (columba livia domestica) with highly pathogenic clade 2.3.4.4 sub-group b h5n8 avian influenza virus.reported mass mortalities in wild pigeons and doves during the 2017/2018 clade 2.3.4.4 hpai h5n8 outbreaks in south africa necessitated an investigation of healthy racing pigeons for their susceptibility and ability to transmit a clade 2.3.4.4 sub-group b virus of south african origin. pigeons challenged with medium (104.5 eid50) and high doses (106 eid50) but not a low dose (103 eid50) of virus, shed virus in low levels of <103 eid50/ml from the oropharynx and cloaca for up to eight days, with ...201830473343
highly diversified shrew hepatitis b viruses corroborate ancient origins and divergent infection patterns of mammalian hepadnaviruses.shrews, insectivorous small mammals, pertain to an ancient mammalian order. we screened 693 european and african shrews for hepatitis b virus (hbv) homologs to elucidate the enigmatic genealogy of hbv. shrews host hbvs at low prevalence (2.5%) across a broad geographic and host range. the phylogenetically divergent shrew hbvs comprise separate species termed crowned shrew hbv (cshbv) and musk shrew hbv (mshbv), each containing distinct genotypes. recombination events across host orders, evolutio ...201931371507
structural differences between the woodchuck hepatitis virus core protein in the dimer and capsid states are consistent with entropic and conformational regulation of assembly.hepadnaviruses are hepatotropic enveloped dna viruses with an icosahedral capsid. hepatitis b virus (hbv) causes chronic infection in an estimated 240 million people; woodchuck hepatitis virus (whv), an hbv homologue, has been an important model system for drug development. the dimeric capsid protein (cp) has multiple functions during the viral life cycle and thus has become an important target for a new generation of antivirals. purified hbv and whv cp spontaneously assemble into 120-dimer caps ...201931043524
discovery of a highly divergent hepadnavirus in shrews from china.limited sampling means that relatively little is known about the diversity and evolutionary history of mammalian members of the hepadnaviridae (genus orthohepadnavirus). an important case in point are shrews, the fourth largest group of mammals, but for which there is limited knowledge on the role they play in viral evolution and emergence. here, we report the discovery of a novel shrew hepadnavirus. the newly discovered virus, denoted shrew hepatitis b virus (shbv), is divergent to be considere ...201930884426
host biology and anthropogenic factors affect hepadnavirus infection in a neotropical bat.the tent-making bat hepatitis b virus (tbhbv) is a hepadnavirus closely related to human hepatitis b virus. the ecology of tbhbv is unclear. we show that it is widespread and highly diversified in peters' tent-making bats (uroderma bilobatum) within panama, while local prevalence varied significantly between sample sites, ranging from 0 to 14.3%. females showed significantly higher prevalence than males, and pregnant females were more often acutely infected than non-reproductive ones. the distri ...201930564998
liver-targeted toll-like receptor 7 agonist combined with entecavir promotes a functional cure in the woodchuck model of hepatitis b virus.current therapeutics for chronic infection with hepatitis b virus (hbv) rarely induce functional cure due to the immunotolerant status of patients. small molecule agonists targeting toll-like receptor 7 (tlr7) have been shown to elicit a functional cure in animal models of hbv but sometimes with poor tolerability due to immune-related toxicities. in an effort to increase the therapeutic window of tlr7 agonists to treat chronic hepatitis b (chb), we developed an oral tlr7 agonist, apr002, designe ...201931592075
cross-reactive and lineage-specific single domain antibodies against influenza b hemagglutinin.influenza b virus (ibv) circulates in the human population and causes considerable disease burden worldwide, each year. current ibv vaccines can struggle to mount an effective cross-reactive immune response, as strains become mismatched, due to constant antigenic changes. additional strategies which use monoclonal antibodies, with broad reactivity, are of considerable interest, both, as diagnostics and as immunotherapeutics. alternatives to conventional monoclonal antibodies, such as single doma ...201931544820
innate and adaptive immunity associated with resolution of acute woodchuck hepatitis virus infection in adult woodchucks.viral and/or host factors that are directly responsible for the acute versus chronic outcome of hepatitis b virus (hbv) infection have not been identified yet. information on immune response during the early stages of hbv infection in humans is mainly derived from blood samples of patients with acute hepatitis b (ahb), which are usually obtained after the onset of clinical symptoms. features of intrahepatic immune response in these patients are less studied due to the difficulty of obtaining mul ...201931869393
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