人疱疹病毒6B入侵肝细胞机理的研究

人疱疹病毒6B(HHV-6B)的原发感染主要发生在6个月到1岁的婴幼儿，引起婴幼儿急诊（exanthem subitum; ES）。原发感染后，病毒在人体内呈潜伏感染，在人体免疫力低下时可反复被激活引起多种疾患。HHV-6B主要感染CD4+ T细胞，近年，HHV-6B引起的肝脏疾患被越来越多地报道。我们进行的体外实验证明HHV-6B能感染肝细胞。2013年，申请人成功地找到了HHV-6B感染CD4+ T细胞的受体和配体，但是该病毒受体在肝细胞表面不表达。本研究拟：1）推测HHV-6B是通过已知受体以外的受体进入肝细胞；2）用已经构建的寻找病毒受体和配体的实验体系来寻找HHV-6B入侵肝细胞的受体和配体；3）详细研究新找到的受体的人体内分布，以及病毒配体受体间的相互作用。我们期望通过本课题的研究能够阐明HHV-6B感染肝细胞的机理，为HHV-6B引起肝脏疾病的基礎研究和临床诊治奠定基础。

Primary infection of Human herpesvirus 6B (HHV-6B) causes exanthem subitum (ES) in little children. After that, it establishes lifelong latency in the host. Reactivation of HHV-6B in immunodeficient or immunocompromised patients always causes severe diseases, like transplant complications, encephalitis and hepatitis. CD4 T cells are the main target of HHV-6B， and hepatocytes are also sensitive to HHV-6B infection. We have identified the cellular receptor (CD134) and viral ligand, glycoprotein (g)H/gL/gQ1/gQ2 complex, for the entry of HHV-6B into CD4 T cells. However, as to its entry into hepatocytes, the cellular receptor and viral ligand are still needed to be elucidated, as CD134 is not expressed on the hepatocyte surface. Here, we plan to identify and analyze this unknown pair of receptor and ligand by using the techniques that we have established. We hope our study will contribute to the development of the therapy and prophylaxis methods for HHV-6B-associated diseases.