Liu Ziqing, Zhao Fang, He Johnny J
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
J Neurovirol. 2014 Jun;20(3):278-93. doi: 10.1007/s13365-014-0245-7. Epub 2014 Mar 27.
Hepatitis C virus (HCV) infection causes the central nervous system (CNS) abnormalities in more than 50 % of chronically infected subjects. However, the underlying mechanisms are largely unknown. In this study, we characterized the HCV interactions with astrocytes, one of the putative HCV target cells in the brain. We demonstrated that primary human astrocytes (PHA) were very inefficiently infected by HCV, either in the cell-free form or through cell-cell contact. We then determined the potential restriction steps of HCV infection and replication in these cells. PHA expressed all known HCV receptors but failed to support HCV entry. HCV IRES-mediated RNA translation was functional in PHA and further enhanced by miR122 expression. Nevertheless, PHA did not support HCV replication regardless of miR122 expression. To our great surprise, we found that HCV exposure induced robust IL-18 expression in PHA and exhibited direct neurotoxicity. Taken together, these results showed that astrocytes did not support productive HCV infection and replication, but HCV interactions with astrocytes and neurons alone might be sufficient to cause CNS dysfunction.
丙型肝炎病毒（HCV）感染在超过50%的慢性感染患者中会导致中枢神经系统（CNS）异常。然而，其潜在机制 largely unknown。在本研究中，我们对HCV与星形胶质细胞（大脑中假定的HCV靶细胞之一）的相互作用进行了表征。我们证明，原代人星形胶质细胞（PHA）无论是以无细胞形式还是通过细胞间接触，都极难被HCV感染。然后，我们确定了HCV在这些细胞中感染和复制的潜在限制步骤。PHA表达所有已知的HCV受体，但不支持HCV进入。HCV IRES介导的RNA翻译在PHA中起作用，并通过miR122的表达进一步增强。然而，无论miR122表达如何，PHA都不支持HCV复制。令我们惊讶的是，我们发现HCV暴露可诱导PHA中强大的IL-18表达，并表现出直接的神经毒性。综上所述，这些结果表明星形胶质细胞不支持HCV的有效感染和复制，但仅HCV与星形胶质细胞和神经元的相互作用可能足以导致CNS功能障碍。
