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
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Tupaia CD81、SR-BI、Claudin-1 和 Occludin 支持丙型肝炎病毒感染
DOI：
10.1128/jvi.01818-10
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发表时间：
2011-03-01
影响因子：
5.4
通讯作者：
Qi, Zhong-Tian
中科院分区：
文献类型：
--
作者：
Tong, Yimin;Zhu, Yongzhe;Qi, Zhong-Tian
摘要丙型肝炎病毒（HCV）相关的研究一直受到缺乏适当的小动物模型的阻碍。据报道，树鼩或树鼩（Tupaia belangeri）可感染血清来源的HCV。然而，这些报告并没有坚定地建立树鼩作为一个可靠的模型HCV感染。人CD 81、I型B类清道夫受体（SR-BI）、封闭蛋白1（CLDN 1）和闭合蛋白（OCLN）被认为是HCV细胞进入的必需受体或辅助受体。在本研究中，这些树鼩直系同源物在HCV感染的作用进行了评估。树鼩的CD 81和SR-BI均能与HCV包膜蛋白2（E2）结合。与人CD 81相比，树鼩 CD 81具有更强的E2结合活性，并使HCV假颗粒（HCVpp）细胞进入增加2倍。用树鼩 CLDN 1转染的293 T细胞变得对HCVpp感染敏感。此外，同时转染四种树鼩因子到小鼠NIH 3 T3细胞中使细胞对HCVpp感染敏感。不同基因型的HCVpp能够感染树鼩原代肝细胞（PTH），并且这种感染可以被抗CD 81或抗SR-BI阻断。PTH可被细胞培养产生的HCV（HCV-HCV）感染，并在培养上清中产生感染性子代病毒。这些发现表明，PTH具有HCV进入所需的所有基本因素，并支持完整的HCV感染周期。这一结果揭示了树鼩对HCV感染的易感机制，并为树鼩作为HCV研究的一种有前景的小动物模型提供了可能。
ABSTRACT 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 (HCVpp) cell entry 2-fold. The 293T cells transfected with tupaia CLDN1 became susceptible to HCVpp infection. Moreover, simultaneous transfection of the four tupaia factors into mouse NIH 3T3 cells made the cells susceptible to HCVpp infection. HCVpp of diverse genotypes were able to infect primary tupaia hepatocytes (PTHs), and this infection could be blocked by either anti-CD81 or anti-SR-BI. PTHs could be infected by cell culture-produced HCV (HCVcc) and did produce infectious progeny virus in culture supernatant. These findings indicate that PTHs possess all of the essential factors required for HCV entry and support the complete HCV infection cycle. This highlights both the mechanisms of susceptibility of tupaia to HCV infection and the possibility of using tupaia as a promising small-animal model in HCV study.