經(jīng)過(guò)4年多的不懈努力,，復(fù)旦大學(xué)免疫生物學(xué)研究所熊思東教授領(lǐng)銜的科研小組在研究乙型肝炎病毒感染人體固有免疫機(jī)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(guó)際著名刊物《肝臟病學(xué)雜志》上,。
科研小組經(jīng)無(wú)數(shù)次體內(nèi)外試驗(yàn)證實(shí)，TRIM22分子對(duì)抑制乙型肝炎病毒復(fù)制,、防止乙型肝炎發(fā)生意義重大,。在進(jìn)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(dòng)子的活性,，從而達(dá)到抑制病毒復(fù)制的目的,，這一成果為深入研究乙型肝炎病毒與機(jī)體免疫系統(tǒng)的相互作用，以及進(jìn)一步闡明臨床常用抗病毒藥物的作用新機(jī)制將產(chǎn)生重大和深遠(yuǎn)的影響,，同時(shí)也將為新一代抗乙型肝炎病毒藥物的設(shè)計(jì)和研制提供新的靶點(diǎn)和研究思路,。
科學(xué)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(duì)它的作用和功能并不了解,。熊思東率領(lǐng)的團(tuán)隊(duì)研究表明，這種新分子其實(shí)是一種對(duì)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(jī)制抑制病毒復(fù)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(shí)有效發(fā)揮作用而導(dǎo)致乙肝病毒感染,，并會(huì)進(jìn)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(guān)研究發(fā)現(xiàn)，干擾素可能就是通過(guò)激發(fā)TRIM22分子,，抑制了乙肝病毒復(fù)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(jī)制，對(duì)科學(xué)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.
