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hepatitis b virus infection of tupaia hepatocytes in vitro and in vivo.for the systematic analysis of various clinical and molecular aspects of hepatitis b virus (hbv) infection, an experimental small animal system of hbv infection would be a great advance. the susceptibility to hbv infection, therefore, of hepatocytes from the tree shrew species tupaia belangeri was studied in vitro and in vivo. primary hepatocytes isolated from livers of tupaias can be reproducibly infected with hbv. in vitro infection results in viral dna and rna synthesis in hepatocytes and sec ...19968707245
an animal study on transmission of hepatitis b virus through mosquitoes.three gena of mosquitoes were fed with human blood infected with hepatitis b virus (hbv) artificially. when blood in the stomach was completely digested, mosquitoes were used to bite monkeys tupaia belangeri. a month after biting, venous blood samples were taken from the monkeys to detect serum hbsag, hbeag, anti-hbs and anti-hbc. among 29 test monkeys, 9 were hbv infective serum markers positive. in 4 of 16 test monkey liver biopsies, acute inflammatory changes were found with hematoxylin-eosin ...19958728939
synergistic effect of hepatitis b virus and aflatoxin b1 in hepatocarcinogenesis in tree shrews.an animal experiment with tree shrews was performed to detect the synergistic effects of hepatitis b virus (hbv) infection and dietary aflatoxin b1 (afb1) in hepatocarcinogenesis. adult healthy tree shrews (tupaia belangeri chinensis) were divided into four groups: group a (hbv + afb1)--animals were infected with human hbv serum at first, then fed afb1 diluted with milk, 150 ug/kg.bw/day, 6 days/week for 105 weeks. group b (hbv)--animals were infected with human hbv as group a, but no afb1 treat ...199910374028
reduction of aflatoxin b(1) adduct biomarkers by oltipraz in the tree shrew (tupaia belangeri chinensis).the risk of liver cancer is greatest in people both infected with hepatitis b virus (hbv) and highly exposed to aflatoxin b(1) (afb(1)). the tree shrew (tupaia belangeri chinensis) is a unique species that can be infected with human hbv, is susceptible to afb(1)-induced liver cancer, and shows a synergistic interaction between hbv and afb(1) for liver cancer. in this regard, the tree shrew may be useful for evaluating experimental chemoprevention strategies relevant to high-risk human population ...200010799742
mutations in the p53 tumor suppressor gene in tree shrew hepatocellular carcinoma associated with hepatitis b virus infection and intake of aflatoxin b1.infection with hepadnaviruses and exposure to aflatoxin b1 (afb1) are considered to be major risk factors in the development of hepatocellular carcinoma (hcc) in humans. a high rate of p53 mutations at codon 249 has been reported in these tumors. the tree shrew (tupaia belangeri chinensis) is a useful animal model for the development of hcc after human hepatitis b virus (hbv) infection or afb1 treatment. therefore, it was of particular interest to determine whether the p53 gene in tree shrew hcc ...200010863098
the tree shrews: adjuncts and alternatives to primates as models for biomedical research.the tree shrews are non-rodent, primate-like, small animals. there is increasing interest in using them to establish animal models for medical and biological research. this review focuses on the use of the tree shrews in in vivo studies on viral hepatitis, hepatocellular carcinoma (hcc), myopia, and psychosocial stress. because of the susceptibility of the tree shrews (tupaia belangeri) and their hepatocytes to infection with human hepatitis b virus (hbv) in vivo and in vitro, these animals have ...200312823622
[differentially expressed genes in hepatocellular carcinoma of tree shrew induced by different factors].previous studies on differentially expressed genes in hepatocellular carcinoma (hcc) used to perform with para-cancerous tissues as normal control. however, the para-cancerous tissue of hcc is actually abnormal because they frequently contain hepatitis, cirrhosis, hyperplastic nodules or foci, etc. in order to explore the molecular mechanism and the responsible genes for hepatocarcinogenesis, through applying the hcc model of tree shrew (tupaia belangeri chinensis), this study was designed to co ...200314558942
chronic infection with hepatitis b viruses and antiviral drug evaluation in upa mice after liver repopulation with tupaia hepatocytes.transplantation of primary human hepatocytes and establishment of hepatitis b virus (hbv) infection in immunodeficient urokinase plasminogen activator (upa) transgenic mice was shown. however, the availability of usable primary human hepatocytes is very limited. therefore, alternative and more accessible sources of hepatocytes permissive for hbv infection are highly desirable. here we investigated the potential of primary hepatocytes from the tree shrew tupaia belangeri that were shown to be sus ...200515629507
lipid-mediated introduction of hepatitis b virus capsids into nonsusceptible cells allows highly efficient replication and facilitates the study of early infection events.the hepatitis b virus (hbv) is an enveloped dna virus which is highly infectious in vivo. in vitro, only primary hepatocytes of humans and tupaia belangeri or the novel heparg cell line are susceptible to hbv, but infection is inefficient and study of early infection events in single cells is unsatisfactory. since hepatoma cells replicate the virus efficiently after transfection, this limited infection efficiency must be related to the initial entry phase. here, we describe the lipid-based deliv ...200616699026
viral and cellular determinants involved in hepadnaviral entry.hepadnaviridae is a family of hepatotropic dna viruses that is divided into the genera orthohepadnavirus of mammals and avihepadnavirus of birds. all members of this family can cause acute and chronic hepatic infection, which in the case of human hepatitis b virus (hbv) constitutes a major global health problem. although our knowledge about the molecular biology of these highly liver-specific viruses has profoundly increased in the last two decades, the mechanisms of attachment and productive en ...200717206752
[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
bats carry pathogenic hepadnaviruses antigenically related to hepatitis b virus and capable of infecting human hepatocytes.the hepatitis b virus (hbv), family hepadnaviridae, is one of most relevant human pathogens. hbv origins are enigmatic, and no zoonotic reservoirs are known. here, we screened 3,080 specimens from 54 bat species representing 11 bat families for hepadnaviral dna. ten specimens (0.3%) from panama and gabon yielded unique hepadnaviruses in coancestral relation to hbv. full genome sequencing allowed classification as three putative orthohepadnavirus species based on genome lengths (3,149-3,377 nt), ...201324043818
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
[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
histopathological changes in the liver of tree shrew (tupaia belangeri chinensis) persistently infected with hepatitis b virus.an animal model for hbv that more closely approximates the disease in humans is needed. the tree shrew (tupaia belangeri) is closely related to primates and susceptible to hbv. we previously established that neonatal tree shrews can be persistently infected with hbv in vivo, and here present a six year follow-up histopathological study of these animals.201324220021
microrna expression in hepatitis b virus infected primary treeshrew hepatocytes and the independence of intracellular mir-122 level for de novo hbv infection in culture.infection of hepatitis b virus (hbv) in hepatocytes has been known to be controlled by multiple cellular factors, while the relationship of the infection and liver micrornas remains obscure. in this study, a mirna database, containing 168 unique mature mirna members from primary hepatocytes of a primate-like animal, northern treeshrew (tupaia belangeri) that is the only species susceptible for hbv infection other than human and chimpanzee, was established. the relative level of a liver predomina ...201424314655
ntcp and beyond: opening the door to unveil hepatitis b virus entry.chronic hepatitis b virus (hbv) infection, affecting approximately 240 million people worldwide, is a major public health problem that elevates the risk of developing liver cirrhosis and hepatocellular carcinoma. given that current anti-hbv drugs are limited to interferon-based regimens and nucleos(t)ide analogs, the development of new anti-hbv agents is urgently needed. the viral entry process is generally an attractive target implicated in antiviral strategies. using primary cells from humans ...201424557582
kinetics of the bile acid transporter and hepatitis b virus receptor na+/taurocholate cotransporting polypeptide (ntcp) in hepatocytes.the human liver bile acid transporter na(+)/taurocholate cotransporting polypeptide (ntcp) has recently been identified as liver-specific receptor for infection of hepatitis b virus (hbv), which attaches via the myristoylated pres1 (myr-pres1) peptide domain of its large surface protein to ntcp. since binding of the myr-pres1 peptide to ntcp is an initiating step of hbv infection, we investigated if this process interferes with the physiological bile acid transport function of ntcp.201424845614
tupaia belangeri as an experimental animal model for viral infection.tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. the morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the tupaiidae. genomic analysis has revealed that the genus tupaia is closer to humans than it is to rodents. in addition, tupaias are susceptible to hepatitis b virus and hepatitis c virus. the only othe ...201425048261
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
hepatitis b virus mutations associated with fulminant hepatitis induce apoptosis in primary tupaia hepatocytes.hepatitis b virus (hbv) core promoter mutations have been implicated in the pathogenesis of fulminant hepatitis b. due to the limited availability of primary human hepatocytes, the functional characterization of hbv mutants has been performed predominantly in transformed cells, which may not represent ideal model systems for studying virus-cell interactions. we and others have shown that primary hepatocytes of the tree shrew tupaia belangeri support hbv infection and replication. in this study, ...200515660384
inhibitory effect of adefovir and lamivudine on the initiation of hepatitis b virus infection in primary tupaia hepatocytes.adefovir dipivoxil and lamivudine are two safe and efficacious drugs licensed for the treatment of chronic hepatitis b virus (hbv) infection. both drugs inhibit the viral polymerase, resulting in a profound suppression of virus production. blocking the viral polymerase may also affect the initiation of hbv infection, because hbv virions harbor a partially double-stranded genome and productive infection requires completion of viral plus-strand dna synthesis with subsequent formation of covalently ...200314647052
pre-s1 antigen-dependent infection of tupaia hepatocyte cultures with human hepatitis b virus.the susceptibility of the tree shrew tupaia belangeri to human hepatitis b virus (hbv) has been demonstrated both in vivo and in vitro. in this study, we show that purified hbv infects primary t. belangeri hepatocyte cultures in a very specific manner, as detected by hbv covalently closed circular dna, mrna, hbv e antigen, and hbsag production. a monoclonal antibody (mab), ma18/7, directed against the pre-s1 domain of the large hbs protein, which has been shown to neutralize infectivity of hbv f ...200312915565
efficient infection of primary tupaia hepatocytes with purified human and woolly monkey hepatitis b virus.the asian tree shrew, tupaia belangeri, has been proposed as a novel animal model for studying hepatitis b virus (hbv) infection. here, we describe a protocol for efficient and reproducible infection of primary tupaia hepatocytes with hbv. we report that human serum interferes with hbv binding to the hepatocytes, thus limiting the maximum multiplicity of infection. purification of hbv virions by gradient sedimentation greatly enhances virus binding and infectivity. covalently closed circular dna ...200111333889
human hepatitis b virus and hepatocellular carcinoma. i. experimental infection of tree shrews with hepatitis b virus.tree shrews (tupaia belangeri chinenesis) can be experimentally infected with human hepatitis b virus (hbv) by inoculation with human serum positive for hbv, the experimental infection rate being 55.21%. successive infections have been passed through five generations among the tree shrews inoculated with hbv-positive sera from the infected animals, the average infection rate being 94.0%. the experimental infection of tree shrews with hbv may be prevented by immunization with hepatitis b vaccine, ...19968609151
strategies to inhibit entry of hbv and hdv into hepatocytes.although there has been much research into the pathogenesis and treatment of hepatitis b virus (hbv) and hepatitis d virus (hdv) infections, we still do not completely understand how these pathogens enter hepatocytes. this is because in vitro infection studies have only been performed in primary human hepatocytes. development of a polarizable, hbv-susceptible human hepatoma cell line and studies of primary hepatocytes from tupaia belangeri have provided important insights into the viral and cell ...201424768844
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
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
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
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
prevention of hepatitis b virus infection in vivo by entry inhibitors derived from the large envelope protein.360 million people are chronically infected with the human hepatitis b virus (hbv) and are consequently prone to develop liver cirrhosis and hepatocellular carcinoma. as approved therapeutic regimens-which modulate patients' antiviral defenses or inhibit the viral reverse transcriptase-are generally noncurative, strategies interfering with other hbv replication steps are required. expanding on our demonstration that acylated peptides derived from the large hbv envelope protein block virus entry ...200818297057
candidate genes responsible for human hepatocellular carcinoma identified from differentially expressed genes in hepatocarcinogenesis of the tree shrew (tupaia belangeri chinesis).aim: to explore gene expression profiles during hepatocarcinogenesis of the tree shrew, and to find the genes responsible for human hepatocellular carcinoma (hcc). methods: tree shrews were used as an animal model for hcc induction employing aflatoxin b(1) (afb(1)) alone or afb(1) plus hepatitis b virus (hbv) as etiological factors. gene expression profiles from the tissues of hcc, hcc-surrounding liver tissues (para-hcc) and the corresponding biopsies taken from the same animals before hcc had ...200817714471
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
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
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
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
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