Transmission of hepatitis C virus infection to tree shrews

Xie, Zhi-Chun; Riezu-Boj, José Ignacio; Lasarte, Juan José; Guillén, Javier; Su, J.H.; Civeira, M.P.; Prìeto, Jesús

doi:10.1016/s0168-8278(98)80603-x

Cited by 11 publications

(11 citation statements)

References 9 publications

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“…Therefore, a single-mutation Leu186F in rat CD81 might suffice HCV permissiveness. The Chinese tree shrew (Tupaia) was previously found permissive for HCV entry, and Tupaia CD81 binds E2 at a comparable level as hCD81 (36). These results agree with our guideline that Tupaia CD81 contains Phe186 and an 188E-196D pair just like hCD81.…”

Section: Discussionsupporting

confidence: 91%

An intramolecular bond at cluster of differentiation 81 ectodomain is important for hepatitis C virus entry

et al. 2015

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Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver diseases; however, HCV vaccine remains unavailable to date. One main obstacle is the lack of an efficient small animal model. Cluster of differentiation 81 (CD81) is an essential entry coreceptor for HCV species specificity to humans, though the underlying mechanisms are yet to be fully elucidated. We performed structural, biophysical, and virologic studies on HCV nonpermissive CD81s from mice and African green monkeys [mouse cluster of differentiation 81 (mCD81) and African green monkey cluster of differentiation 81 (agmCD81)] and compared with human cluster of differentiation 81 (hCD81). We discovered an intramolecular hydrogen bond (Gln188-Nε2-H: Glu196-Oε2, 2 Å, 124°) within the large extracellular loop (LEL) of mCD81 and a salt bridge (Lys188-Nζ: Asp196-Oδ2, 2.4 Å) within agmCD81-LEL between residues 188 and 196. This structural feature is missing in hCD81. We demonstrated that the introduction of a single 188-196 bond to hCD81 impaired its binding affinity to HCV envelope glycoprotein 2 (HCV E2) and significantly decreased HCV pseudoviral particle (HCVpp) entry efficiency (4.92- to 8.42-fold) and cell culture-grown HCV (HCVcc) infectivity (4.55-fold), despite the availability of Phe186. For HCV nonpermissive CD81s, the introduction of Phe186 by Leu186F substitution alone was insufficient to confer HCV permissiveness. The disruption of the original 188-196 bond and Leu186F substitution were both required for potent binding to HCV E2 HCVpp entry efficiency and HCVcc infectivity. Our structural and biophysical analyses suggest that the intramolecular 188-196 bond restricts the intrinsic conformational dynamics of D-helix of CD81-LEL, which is essential for HCV entry, thus impairs HCV permissiveness. Our findings reveal a novel molecular determinant for HCV entry in addition to the well-characterized Phe186 and provide further guideline for selecting an HCV small animal model.

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Section: Discussionsupporting

confidence: 91%

An intramolecular bond at cluster of differentiation 81 ectodomain is important for hepatitis C virus entry

et al. 2015

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“…T UPAIA (TUPAIA BELANGERI chinensis), a small primate resembling the squirrel, has been reported to be susceptible to hepatitis B virus (HBV) infection in 1996, 3 and was used for the study of HCV infection. 7 However, only a quarter of inoculated individuals con-tracted HCV infection, and developed only a transient or intermittent viremia with low viral loads. Another study group reported on the usefulness of how a primary culture of hepatocytes from the liver of Tupaia can be infected with serum-or plasma-derived HCV from infected humans, as measured by de novo synthesis of HCV RNA, analysis of viral quasispecies evolution, and detection of viral proteins.…”

Section: The Small Primates Modelmentioning

confidence: 99%

Animal models for hepatitis C and related liver disease

Koike¹,

Moriya²,

Matsuura³

2010

Hepatology Research

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Persistent infection with hepatitis C virus (HCV) is a major risk toward development of hepatocellular carcinoma (HCC). The elucidation of pathogenesis of HCV-associated liver disease is hampered by the absence of appropriate animal models: there has been no animal model for HCV infection/pathogenesis except for the chimpanzee. In contrast, a number of transgenic mouse lines carrying the cDNA of the HCV genome have been established and evaluated in the study of HCV pathogenesis. The studies using transgenic mouse models, in which the HCV proteins such as the core protein are expressed, indicate the direct pathogenicity of HCV, including oncogenic activities. HCV transgenic mouse models also show a close relationship between HCV and some hepatic and extrahepatic manifestations such as hepatic steatosis, insulin resistance or Sjögren's syndrome. A crucial role of hepatic steatosis and insulin resistance in the pathogenesis of liver disease in HCV infection has been demonstrated, implying hepatitis C to be a metabolic disease. Besides the data connecting liver fibrosis progression and the disturbance in lipid and glucose metabolisms in hepatitis C patients, a series of evidence was found showing the association between these two conditions and HCV infection, chiefly using transgenic mouse carrying the HCV genome. Furthermore, the persistent activation of peroxisome proliferator-activated receptor (PPAR)-alpha has recently been found, yielding dramatic changes in the lipid metabolism and oxidative stress overproduction in cooperation with the mitochondrial dysfunction. These results would provide a clue for further understanding of the role of lipid metabolism in pathogenesis of hepatitis C including liver injury and hepatocarcinogenesis.

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“…After whole-body irradiation, the efficiency of infection in the tree shrews may be increased. These animals may serve as an in vivo system for culturing human HCV and addressing pathophysiological and therapeutic issues of HCV infection [52]. Currently, an animal model for HCV-associated HCC has not been established in the tree shrews yet.…”

Section: Virus Hepatitis Modelmentioning

confidence: 99%

The tree shrews: adjuncts and alternatives to primates as models for biomedical research

Cao

Yang

et al. 2003

J of Medical Primatology

151

111

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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 been used to establish human hepatitis virus-induced hepatitis and human HBV- and aflatoxin B1-associated HCC models. As these animals are phylogenetically close to primates in evolution and have a well-developed visual system and color vision in some species, they have been utilized to establish myopia models. Because dramatic behavioral, physiological, and neuroendocrine changes in subordinate male tree shrews are similar to those observed in depressed human patients, the tree shrews have been successfully employed to experimentally study psychosocial stress. However, the tree shrews holds significant promise as research models and great use could be made of these animals in biomedical research.

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Transmission of hepatitis C virus infection to tree shrews

Cited by 11 publications

References 9 publications

An intramolecular bond at cluster of differentiation 81 ectodomain is important for hepatitis C virus entry

An intramolecular bond at cluster of differentiation 81 ectodomain is important for hepatitis C virus entry

Animal models for hepatitis C and related liver disease

The tree shrews: adjuncts and alternatives to primates as models for biomedical research

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