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

Tian, Zhan-Fei; Shen, Hong; Fu, Xihua; Chen, Yi‐Chun; Blum, Hubert E.; Baumert, Thomas F.; Zhao, Xingwei

doi:10.3748/wjg.15.240

Cited by 12 publications

(3 citation statements)

References 32 publications

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“…The EIA and flow cytometry assay for E2-CD81 binding also showed that HCV E2 bound to the tupaia CD81 LEL much more strongly than to the human CD81 LEL. These results are in contrast to a recent finding that the binding of the tupaia CD81 LEL glutathione S-transferase (GST) fusion protein to the HCV E2 protein was markedly reduced compared with that of human CD81 LEL GST (35). In this recent report, the recombinant human CD81 LEL and tupaia CD81 LEL were obtained from different research groups, while in the present study, both CD81 LEL were prepared under the same conditions.…”

Section: Discussioncontrasting

confidence: 80%

Tupaia CD81, SR-BI, Claudin-1, and Occludin Support Hepatitis C Virus Infection

Tong

Zhu

Xia

et al. 2011

J Virol

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Hepatitis C virus (HCV)-related research has been hampered by the lack of appropriate small-animal models. It has been reported that tree shrews, or tupaias (Tupaia belangeri), can be infected with serum-derived HCV. However, these reports do not firmly establish the tupaia as a reliable model of HCV infection. Human CD81, scavenger receptor class B type I (SR-BI), claudin 1 (CLDN1), and occludin (OCLN) are considered essential receptors or coreceptors for HCV cell entry. In the present study, the roles of these tupaia orthologs in HCV infection were assessed. Both CD81 and SR-BI of tupaia were found to be able to bind with HCV envelope protein 2 (E2). In comparison with human CD81, tupaia CD81 exhibited stronger binding activity with E2 and increased HCV pseudoparticle ( Hepatitis C virus (HCV) is a major cause of liver disease. A total of 170 million individuals worldwide are estimated to be infected with HCV and are at risk of developing cirrhosis and hepatocellular carcinoma (32,33). Unfortunately, there is presently no effective HCV vaccine available, and current treatments are far from satisfactory (22, 28). The development of antiviral therapies and effective vaccines has been hampered greatly by the lack of a convenient small-animal model. Chimpanzees (Pan troglodytes) are the only nonhuman primate host serving as an HCV infection model. However, experiments using chimpanzees are both expensive and ethically problematic. To date, three small-animal models of HCV infection have been reported: the immunotolerized rat model, Trimera mouse model, and uPA/SCID mouse model (16,25,39). However, these models are difficult to prepare, and the abnormal immune status of each greatly limits their application.The tree shrew or tupaia (Tupaia belangeri) is a small, squirrel-like mammal that is closely related to primates (6). Since the 1980s, tupaias have been used as an animal model of various infectious agents and their associated diseases. Tupaia has been shown to be susceptible to a variety of human viruses, including herpes simplex virus and hepatitis B virus (HBV) (9,38). Early in 1998 it was reported that inoculation with HCV RNA-positive serum could lead to short-term viremia and the appearance of anti-HCV IgG in tupaia (40). Furthermore, primary tupaia hepatocytes (PTHs) can be infected in vitro with serum derived from chronic hepatitis C patients (2, 18, 21, 36), although it is not clear whether the viral RNA measured is due to de novo production and/or from the virus inoculum. Recently, independent observations showed that inoculating tupaia with hepatitis C patient serum or viral particles reconstituted from full-length HCV cDNA caused mild hepatitis and intermittent viremia (1). However, these reports do not firmly establish the tupaia as a reliable model of HCV replication and pathogenesis. Importantly, patient sera often exhibit very weak infectivity (15,36). Although these results show promise, additional work has to be conducted to evaluate the value of pursuing the tupaia system in HCV research.The e...

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Section: Discussioncontrasting

confidence: 80%

Tupaia CD81, SR-BI, Claudin-1, and Occludin Support Hepatitis C Virus Infection

Tong

Zhu

Xia

et al. 2011

J Virol

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“…However, the Huh-7w7 cell line, which does not express hCD81, can be infected by HCV when stably expressing mCD81 without any adaptation [ 75 ]. It has to be noted that tupaïa CD81 has been shown to be functional in HCV entry and tupaïa primary hepatocytes support full HCV infection [ 125 , 126 , 127 , 128 , 129 ], making of tupaia a new hope to develop a simpler animal model.…”

Section: Cd81 Plays a Major Role In Hcv Entrymentioning

confidence: 99%

CD81 and Hepatitis C Virus (HCV) Infection

Fénéant

Levy

Cocquerel

2014

Viruses

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Hepatitis C Virus (HCV) infection is a global public health problem affecting over 160 million individuals worldwide. Its symptoms include chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped RNA virus mainly targeting liver cells and for which the initiation of infection occurs through a complex multistep process involving a series of specific cellular entry factors. This process is likely mediated through the formation of a tightly orchestrated complex of HCV entry factors at the plasma membrane. Among HCV entry factors, the tetraspanin CD81 is one of the best characterized and it is undoubtedly a key player in the HCV lifecycle. In this review, we detail the current knowledge on the involvement of CD81 in the HCV lifecycle, as well as in the immune response to HCV infection.

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“…Early studies showed that tree shrew primary hepatocytes could be infected by HCV (11)(12)(13), and a high infection rate (.80%) was observed in the tree shrews challenged with patient-or cell culture-derived HCV (14). The tree shrew orthologs of vital HCV entry factors, such as CD81 (15), SR-BI (16), claudin-1, and occludin (17), supported HCV infection. However, infected animals frequently progressed to a low level of illness severity, with only a few animals developing severe liver disease after 3 y following the initial HCV infection (14).…”

mentioning

confidence: 99%

Tupaia MAVS Is a Dual Target during Hepatitis C Virus Infection for Innate Immune Evasion and Viral Replication via NF-κB

Yao

et al. 2020

The Journal of Immunology

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Hepatitis C virus (HCV) infection is the cause of severe liver disease in many people. The restricted species tropism of HCV hinders the research and development of drugs and vaccines. The Chinese tree shrew (Tupaia belangeri chinensis) is a close relative of primates and can be infected by HCV, but the underlying mechanisms are unknown. In this study, we have characterized the functions of tree shrew MAVS (tMAVS) in response to HCV infection and defined the capacity of HCV replication. HCV was shown to be colocalized with tMAVS in primary tree shrew hepatocytes and cleaved tMAVS at site Cys508 via its NS3/4A protease, with a modulating effect by site Glu506 of tMAVS. The tMAVS cleavage by HCV NS3/4A impaired the IRF3-mediated induction of IFN-β but maintained the activated NF-κB signaling in the tree shrew primary cells. Activation of the tMAVS-dependent NF-κB signaling inversely inhibited HCV replication and might limit the establishment of persistent infection. Overall, our study has revealed an elegant example of the balance between the host defenses and HCV infection via the MAVS-mediated antiviral signaling and has provided an insight into the mechanisms underpinning HCV infection in the Chinese tree shrew.

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

Cited by 12 publications

References 32 publications

Tupaia CD81, SR-BI, Claudin-1, and Occludin Support Hepatitis C Virus Infection

Tupaia CD81, SR-BI, Claudin-1, and Occludin Support Hepatitis C Virus Infection

CD81 and Hepatitis C Virus (HCV) Infection

Tupaia MAVS Is a Dual Target during Hepatitis C Virus Infection for Innate Immune Evasion and Viral Replication via NF-κB

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