[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.

hantavirus

Rojjer发表于 2009-9-3 21:18 ：

呵呵，免疫学界的帅教授，知识渊博、思维敏捷、风度翩翩，在女生中可是相当受欢迎。
好久没听过他讲课了，呵呵，不过这个周六他会来我们所给我们做个
学术报告（基因疫苗研发中的几个基本问题）。
其实个人觉得他要是能把全部精力放到科研上面肯定会有比现在大得多的学术成就。
总觉得他有点想走明星路线的感觉，又是政协委员、复旦学院院长、搞通识教育还教马克思主义课程呢。呵呵
不过自己还是挺佩服熊思东教授的，一步一步从小地方走出来的高水平教授！

hantavirus

giggle334 发表于 2009-9-3 21:08 ：熊思东教授牛人一个 前不久听过他在兰大做的学术报告 特别精彩 条理清晰  思维广阔 佩服佩服！！  

hantavirus

Rojjer发表于 2009-9-3 20:04 ：


IF：10.734
算是熊思东教授这几年来的一份大手笔！
查了一下相关资料，TRIM22分子在HIV的研究中相对集中，也首先在HIV'的研究中发现具有抗病毒潜能。
近年也是成为抗HIV药物开发的靶点。
Tripartite motif-containing 22, also known as TRIM22, is a protein which in humans is encoded by the TRIM22 gene.
The protein encoded by this gene is a member of the tripartite motif (TRIM) family.The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the cytoplasm and its expression is induced by interferon.
TRIM22 is also a target gene of the tumor suppressor protein p53，TRIM22 possesses E3 ubiquitin ligase activity and is able to ubiquitinate itself with the assistance of the E2 enzyme UbcH5B. Furthermore TRIM22 is located in the nucleus and therefore may function as a nuclear E3 ubiquitin ligase.

References:

^ a b c "Entrez Gene: TRIM22 tripartite motif-containing 22". http://www.ncbi.nlm.nih.gov/site ... TermToSearch=10346.  
^ a b Tissot C, Mechti N (June 1995). "Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression". J. Biol. Chem. 270 (25): 14891–8. PMID 7797467. http://www.jbc.org/cgi/content/full/270/25/14891.  
^ Gongora C, Tissot C, Cerdan C, Mechti N (November 2000). "The interferon-inducible Staf50 gene is downregulated during T cell costimulation by CD2 and CD28". J. Interferon Cytokine Res. 20 (11): 955–61. doi:10.1089/10799900050198390. PMID 11096452.  
^ Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG, Ballabio A (May 2001). "The tripartite motif family identifies cell compartments". EMBO J. 20 (9): 2140–51. doi:10.1093/emboj/20.9.2140. PMID 11331580.  
^ Obad S, Olofsson T, Mechti N, Gullberg U, Drott K (October 2007). "Regulation of the interferon-inducible p53 target gene TRIM22 (Staf50) in human T lymphocyte activation". J. Interferon Cytokine Res. 27 (10): 857–64. doi:10.1089/jir.2006.0180. PMID 17970695. http://luur.lub.lu.se/luur?func=downloadFile&fileOId=548138.  
^ Duan Z, Gao B, Xu W, Xiong S (September 2008). "Identification of TRIM22 as a RING finger E3 ubiquitin ligase". Biochem. Biophys. Res. Commun. 374 (3): 502–6. doi:10.1016/j.bbrc.2008.07.070. PMID 18656448.  
^ Huthoff H, Towers GJ (December 2008). "Restriction of retroviral replication by APOBEC3G/F and TRIM5alpha". Trends Microbiol. 16 (12): 612–9. doi:10.1016/j.tim.2008.08.013. PMID 18976920.  
^ "Researchers discover gene that blocks HIV". Medicine & Health / HIV & AIDS. PhysOrg.com. 2008-02-29. http://www.physorg.com/news123505489.html. Retrieved 2009-02-22.  
^ Barr SD, Smiley JR, Bushman FD (February 2008). "The interferon response inhibits HIV particle production by induction of TRIM22". PLoS Pathog. 4 (2): e1000007. doi:10.1371/journal.ppat.1000007. PMID 18389079