Primary hepatocytes of Tupaia belangeri as a potential model for hepatitis C virus infection

Zhao, Xi; Tang, Zhenya; Klumpp, Bettina; Wolff-Vorbeck, Guido; Barth, Heidi; Levy, Shoshana; Weizsäcker, Fritz von; Blum, Hubert E.; Baumert, Thomas F.

doi:10.1172/jci200213011

Cited by 36 publications

(69 citation statements)

References 41 publications

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“…Hepatitis C is caused by the HCV, another worldwide infectious disease 34 . Except for chimpanzees, there are many reports that tree shrew and its hepatocytes could be infected with human HBV 4 and HCV 3 . Hence, the property of genes involved in immunity response of viral infection demonstrated by tree shrews further contributes to their preferred choice as an attractive model for studying viral hepatitis and hepatocellular carcinoma 35 .…”

Section: Resultsmentioning

confidence: 99%

“…The publicly available annotated genome sequence of the Chinese tree shrew we generated offers an opportunity to decipher the genetic basis of the tree shrews' suitability as an animal model for studying depression, myopia and viral infection [3][4][5][6][7] . Although we did not provide further experimental evidence to solidify the speculations deducted from the comparative genomics, the unique genetic features that we discerned from the genome of Chinese tree shrew has provided insightful information for us to understanding the biology of this animal.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, there are many attempts to employ tree shrew to create animal models for studying hepatitis C virus (HCV) 3 and hepatitis B virus (HBV) infections 4 , myopia 5 , as well as social stress and depression 6,7 . Recent studies of aged tree shrew brain suggested that tree shrew is also a valid model for aging research 8 and learning behaviours 9 .…”

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confidence: 99%

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Genome of the Chinese tree shrew

et al. 2013

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Chinese tree shrews (Tupaia belangeri chinensis) possess many features valuable in animals used as experimental models in biomedical research. Currently, there are numerous attempts to employ tree shrews as models for a variety of human disorders: depression, myopia, hepatitis B and C virus infections, and hepatocellular carcinoma, to name a few. Here we present a publicly available annotated genome sequence for the Chinese tree shrew. Phylogenomic analysis of the tree shrew and other mammalians highly support its close affinity to primates. By characterizing key factors and signalling pathways in nervous and immune systems, we demonstrate that tree shrews possess both shared common and unique features, and provide a genetic basis for the use of this animal as a potential model for biomedical research.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genome of the Chinese tree shrew

et al. 2013

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“…Using this cell culture system, we found that HCV E2 protein binding to PTHs and infection of PTHs with HCV could not be blocked with soluble CD81 and anti-CD81 [25] . To further investigate the role of CD81 in the infection of PTHs with HCV, we cloned a tupaia CD81 large extracellular loop (LEL) and analyzed the interaction of tupaia CD81 with HCV E2 protein in vitro.…”

Section: Introductionmentioning

confidence: 94%

“…Recently, a novel in vitro cell culture model system has been established for HCV with primary tupaia hepatocytes (PTHs) [25][26][27] . Using this cell culture system, we found that HCV E2 protein binding to PTHs and infection of PTHs with HCV could not be blocked with soluble CD81 and anti-CD81 [25] .…”

Section: Introductionmentioning

confidence: 99%

Interaction of hepatitis C virus envelope glycoprotein E2 with the large extracellular loop of tupaia CD81

Tian¹,

Shen²,

Fu³

et al. 2009

WJG

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AIM:To further analyze the interaction of tupaia CD81 with hepatitis C virus (HCV) envelope protein E2. METHODS:A tupaia CD81 large extracellular loop (CD81 LEL), which binds to HCV E2 protein, was cloned and expressed as a GST-fusion protein, and interaction of HCV E2 protein with a tupaia CD81 LEL was evaluated by enzyme-linked immunosorbent assay (EIA). RESULTS:Although tupaia and human CD81 LEL differed in 6 amino acid changes, tupaia CD81 LEL was strongly recognized by anti-CD81 antibodies against human CD81 LEL conformation-dependent epitopes. Investigating LEL CD81-E2 interactions by EIA, we demonstrated that binding of tupaia CD81 LEL GST fusion protein to recombinant HCV E2 protein was markedly reduced compared to binding of human CD81 LEL GST fusion protein to recombinant HCV E2 protein. CONCLUSION:These data suggest that the structural differences in-between the tupaia and human CD81 may alter the interaction of the large extracellular loop with HCV envelope glycoprotein E2. These findings may be important for the understanding of the mechanisms of binding and entry of HCV to PTHs.

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Immunohistochemical mapping of neuropeptide Y in the tree shrew brain

Shu

Luo

et al. 2014

J of Comparative Neurology

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Day-active tree shrews are promising animals as research models for a variety of human disorders. Neuropeptide Y (NPY) modulates many behaviors in vertebrates. Here we examined the distribution of NPY in the brain of tree shrews (Tupaia belangeri chinensis) using immunohistochemical techniques. The differential distribution of NPY-immunoreactive (-ir) cells and fibers were observed in the rhinencephalon, telencephalon, diencephalon, mesencephalon, metencephalon, and myelencephalon of tree shrews. Most NPY-ir cells were multipolar or bipolar in shape with triangular, fusiform, and/or globular perikarya. The densest cluster of NPY-ir cells were found in the mitral cell layer of the main olfactory bulb (MOB), arcuate nucleus of the hypothalamus, and pretectal nucleus of the thalamus. The MOB presented a unique pattern of NPY immunoreactivity. Laminar distribution of NPY-ir cells was observed in the MOB, neocortex, and hippocampus. Compared to rats, the tree shrews exhibited a particularly robust and widespread distribution of NPY-ir cells in the MOB, bed nucleus of the stria terminalis, and amygdala as well as the ventral lateral geniculate nucleus and pretectal nucleus of the thalamus. By contrast, a low density of neurons were scattered in the striatum, neocortex, polymorph cell layer of the dentate gyrus, superior colliculus, inferior colliculus, and dorsal tegmental nucleus. These findings provide the first detailed mapping of NPY immunoreactivity in the tree shrew brain and demonstrate species differences in the distribution of this neuropeptide, providing an anatomical basis for the participation of the NPY system in the regulation of numerous physiological and behavioral processes.

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Primary hepatocytes of Tupaia belangeri as a potential model for hepatitis C virus infection

Cited by 36 publications

References 41 publications

Genome of the Chinese tree shrew

Genome of the Chinese tree shrew

Interaction of hepatitis C virus envelope glycoprotein E2 with the large extracellular loop of tupaia CD81

Immunohistochemical mapping of neuropeptide Y in the tree shrew brain

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