已知我国HCC的发生与CHB肝硬化、黄曲霉毒素、饮用沟塘水密切相关。随着城镇化高速推进，后两个致HCC因素已获较好控制，但HCC发病率仍居高不下，提示HCC的发生存在其他促发因素。这个未知的促发因素是什么？CHB肝硬化时机体免疫功能下降，此时肝组织存在HVEM高表达，形成局部“免疫抑制微环境”。我们的实验显示此时HCC癌周肝组织、癌细胞中均存在HHV-6b高感染。进一步的FISH实验显示HHV-6b可存在于细胞核内，并在染色体端粒位置整合。由此，我们首次提出：HHV-6b是CHB肝硬化HVEM高表达时HCC发生的重要促发病原体，免疫抑制微环境是重要基础。本项目拟进一步采用定量PCR、FISH技术和树鼩等展开研究，旨在获得HHV-6b是癌变重要促发病原体的可靠证据。本项目将阐明HHV-6b参与HCC发生的机制和影响因素，为确立HHV-6b作为防控HCC发生的重要病原体提供更充分的科学依据。

It is well known that the occurrence of HCC in China is closely related to CHB associated cirrhosis, aflatoxin and Pond-ditch water. With rapid urbanization, the latter two factors have been well controlled while the incidence of HCC is still high, which indicating that there must be other unknown inducing factors. But, what’s it? Or, what are they? Patients with CHB associated cirrhosis are in a status of declined immune function with high expression of HVEM gene in liver cells, resulting in T-cell immune dysfunction and forming an immunosuppressive microenvironment in local tissue. Our previous study has found the high positive rates of HHV-6b in both peritumoral liver tissue and HCC tissue samples. FISH experiments further confirmed that HHV-6b sequence was presented in the nuclei and integrated in telomeres of human chromosomes. Therefore, we propose that the CHB associated cirrhosis would promote the expression of HVEM gene, resulting in T-cell immune dysfunction and forming an immunosuppressive microenvironment, leading to HHV-6b infection in liver tissue and finally induces the malignant transformation of hepatocytes. The main aim of this project is to identify that HHV-6b is an important pathogen in the carcinogenesis of HCC through RT-PCR, FISH technology, tree shrew animal model, and so on. By elucidating the new mechanism of HCC promoted by HHV-6b, we believe this project would provide solid evidences that HHV-6b is an important pathogen of carcinogenesis for preventing and controlling the development of HCC.