[转移帖]我国科学家首次发现抗乙肝病毒感染新机制

hantavirus

原帖由bigben发表于 2009-9-3 19:09：

http://www.sina.com.cn  2009年09月03日17:23  新华网
　　新华网上海9月3日电(仇逸、孙国根) 经过4年多的不懈努力，复旦大学免疫生物学研究所熊思东教授领衔的科研小组在研究乙型肝炎病毒感染人体固有免疫机制中，发现人体内的TRIM22分子在抗乙型肝炎病毒感染中有重要作用，这一研究成果已发表在最新一期的国际著名刊物《肝脏病学杂志》上。

　　科研小组经无数次体内外试验证实，TRIM22分子对抑制乙型肝炎病毒复制、防止乙型肝炎发生意义重大。在进一步研究中发现，TRIM22可明显抑制乙型肝炎病毒核心启动子的活性，从而达到抑制病毒复制的目的，这一成果为深入研究乙型肝炎病毒与机体免疫系统的相互作用，以及进一步阐明临床常用抗病毒药物的作用新机制将产生重大和深远的影响，同时也将为新一代抗乙型肝炎病毒药物的设计和研制提供新的靶点和研究思路。

　　科学家新近研究发现，人体内普遍存在着一种TRIM22分子，但人们对它的作用和功能并不了解。熊思东率领的团队研究表明，这种新分子其实是一种对人体有益的固有免疫分子。有的人感染乙肝病毒后，能迅速激发体内固有免疫和特异免疫机制抑制病毒复制，清除乙肝病毒，从而痊愈，其中TRIM22分子起了重要作用；而另一部分人感染乙肝病毒后，因体内TRIM22分子不能适时有效发挥作用而导致乙肝病毒感染，并会进一步发展为慢性肝炎，甚至肝癌。

　　此外，目前干扰素是治疗慢性乙肝的有效药物之一，相关研究发现，干扰素可能就是通过激发TRIM22分子，抑制了乙肝病毒复制。研究成果首次揭示了人体抵抗乙肝病毒感染的重要固有免疫机制，对科学界继续研发新一代抗乙肝病毒感染药物有重要意义。

http://www.ncbi.nlm.nih.gov/pubmed/19585648
Hepatology. 2009 Aug;50(2):424-33

Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear-located RING domain.

Gao B, Duan Z, Xu W, Xiong S.
Department of Immunology, Institute for Immunobiology, Shanghai Medical College of Fudan University, People's Republic of China.

Members of the tripartite motif (TRIM) family are a part of the innate immune system to counter intracellular pathogens. TRIM22 has been reported to possess antiretroviral activity. Here we report that TRIM22 is involved in antiviral immunity against hepatitis B virus (HBV). Our results showed that TRIM22, being a strongly induced gene by interferons in human hepatoma HepG2 cells, could inhibit HBV gene expression and replication in a cell culture system as well as in a mouse model system. Importantly, it was found that TRIM22 could inhibit the activity of HBV core promoter (CP) in a dose-dependent manner. However, TRIM22 lacking the C terminal SPRY domain lost this activity. Further study showed that the SPRY domain deletion mutant was localized exclusively to the cytoplasm of HepG2 cells. In contrast, the wild-type TRIM22 was localized to the nucleus, as expected for a transcriptional suppressor. Interestingly, although RING domain mutants of TRIM22 were localized to the nucleus, they could not inhibit HBV CP activity, indicating that TRIM22-mediated anti-HBV activity was dependent on the nuclear-located RING domain. CONCLUSION: These findings suggest that TRIM22, which exhibits anti-HBV activity by acting as a transcriptional suppressor, may play an important role in the clearance of HBV.