經(jīng)過4年多的不懈努力，復旦大學免疫生物學研究所熊思東教授領銜的科研小組在研究乙型肝炎病毒感染人體固有免疫機制中,，發(fā)現(xiàn)人體內(nèi)的TRIM22分子在抗乙型肝炎病毒感染中有重要作用，這一研究成果已發(fā)表在最新一期的國際著名刊物《肝臟病學雜志》上,。
科研小組經(jīng)無數(shù)次體內(nèi)外試驗證實,，TRIM22分子對抑制乙型肝炎病毒復制、防止乙型肝炎發(fā)生意義重大,。在進一步研究中發(fā)現(xiàn),，TRIM22可明顯抑制乙型肝炎病毒核心啟動子的活性，從而達到抑制病毒復制的目的,，這一成果為深入研究乙型肝炎病毒與機體免疫系統(tǒng)的相互作用,，以及進一步闡明臨床常用抗病毒藥物的作用新機制將產(chǎn)生重大和深遠的影響，同時也將為新一代抗乙型肝炎病毒藥物的設計和研制提供新的靶點和研究思路,。
科學家新近研究發(fā)現(xiàn),，人體內(nèi)普遍存在著一種TRIM22分子，但人們對它的作用和功能并不了解,。熊思東率領的團隊研究表明,，這種新分子其實是一種對人體有益的固有免疫分子。有的人感染乙肝病毒后,，能迅速激發(fā)體內(nèi)固有免疫和特異免疫機制抑制病毒復制,，清除乙肝病毒,，從而痊愈，其中TRIM22分子起了重要作用,；而另一部分人感染乙肝病毒后,，因體內(nèi)TRIM22分子不能適時有效發(fā)揮作用而導致乙肝病毒感染，并會進一步發(fā)展為慢性肝炎,，甚至肝癌,。
此外，目前干擾素是治療慢性乙肝的有效藥物之一,，相關研究發(fā)現(xiàn)，干擾素可能就是通過激發(fā)TRIM22分子,，抑制了乙肝病毒復制,。研究成果首次揭示了人體抵抗乙肝病毒感染的重要固有免疫機制，對科學界繼續(xù)研發(fā)新一代抗乙肝病毒感染藥物有重要意義,。（生物谷Bioon.com）
生物谷推薦原始出處：
Hepatology Volume 50 Issue 2, Pages 424 - 433
Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear-located RING domain
Bo Gao 1, Zhijian Duan 1, Wei Xu 1, Sidong Xiong 1 2 *
1Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, People's Republic of China
2Immunology Division, E-Institutes of Shanghai Universities, Shanghai, 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.
