HIV病毒 z-bo 2020-11-03 361

　　Previous studies have shown that RNA-protein interactions play an important role in the formation of HIV virus particles. HIV-1 Gag is the main structural protein of HIV, with RNA binding sites (nucleocapsid domain, NC). By binding to HIV RNA, Gag protein can use RNA as a scaffold and polymerize in large numbers on the host cell membrane, eventually forming thousands of Virus particles of Gag (Figure 1A). Further studies have shown that Gag can also non-specifically bind to other RNAs, such as long-stranded RNA in cells, and that the longer the RNA chain that supports Gag polymerization, the larger the virus particles formed. Based on this, Chen Kuangshi and others put forward the hypothesis that the high expression of cell’s own micrornA (a small non-coding RNA with a length of only about 22 nucleotides) can force microRNA to bind non-specifically with HIV-1 Gag protein, thereby interfering with Gag and Gag. The combination of long-chain RNA inhibits the formation and spread of HIV virus particles.

　　Combining high-resolution fluorescence microscopy technology, cell biology, and biochemical methods, Chen Kuangshi and his collaborators confirmed that microRNA can bind to Gag to form a microRNA-Gag complex, and that the complex can destroy the Gag assembly platform, preventing the effective release of virus particles. The Gag platform that fails to assemble will not be able to resist the endocytosis of the cell and will accumulate in the lysosomes and eventually be degraded.

　　Different from the general understanding of microRNA function (targeting specific mRNA and causing gene silencing) in previous studies, Chen Kuangshi and others found that microRNA can "non-specifically" block the formation of HIV virus particles. This new mechanism is expected to provide new ideas for the treatment of diseases caused by AIDS or other retroviruses. Part of this work was completed at Peking University and was funded by the National Natural Science Foundation of China and the Thousand Young Talents Startup Fund.

　　Chen Kuangshi joined the School of Engineering of Peking University in April 2013. He is a distinguished researcher of the Department of Biomedical Engineering and the first author of the paper. His research direction is the scientific issues related to cell and molecular imaging. The current main research content is the research and development of RNA molecular probe technology, exploring the effects of RNA-protein interaction on cell physiology and disease occurrence, virus and host cell interaction, molecular medicine Wait.