HIV病毒,miRNA z-bo 2020-09-15 356

　　Recently, researchers from Peking University collaborated with HIV virologists in the United States and discovered that miRNA has the potential to resist HIV infection. The research results have been published in PNAS.

　　Studies have shown that RNA-protein interaction plays 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 Gag virus particles. Further studies have shown that Gag will non-specifically bind to other RNAs during the polymerization process, using RNA as a support for polymerization. The longer the RNA chain, the more Gag aggregates and the larger the virus particle formed. The researchers first put forward the hypothesis that if some special miRNA of the cell itself is increased, it may force the miRNA to bind non-specifically with the HIV-1 Gag protein, thereby interfering with the binding of Gag to the RNA supporting the backbone, preventing Gag polymerization, and ultimately inhibiting the HIV virus. The purpose of particle formation and propagation.

　　Combined with high-resolution fluorescence microscopy technology, the researchers first confirmed that, without changing the abundance of Gag mRNA, by increasing the abundance of miRNAs with low or no expression in some host cells and no binding sites on the HIV virus genome transcript It can inhibit the release ability of new HIV virus particles; further through experiments such as gene knockout, FISH, and co-IP, the researchers confirmed that, including miR-146a, miR-17, miR-19 and miR-16 and other miRNAs Both bind to Gag through the miRNA silencing complex, destroying the aggregation and assembly of Gag, so that the virus particles cannot be effectively released. The Gag platform that fails to assemble will not be able to resist the endocytosis of the cell and will be degraded by the lysosomes gathered.

　　The general understanding of miRNA function is different. This study proves that miRNA can not only play a special regulatory role by binding miRNA silencing complex to the seed sequence of the 3'UTR region of the target gene, but also act as a ligand and some special protein receptors. Combine to play some special functions. This research provides new ideas for preventing HIV and other retroviruses from replicating and spreading. In the future, researchers may be able to develop and design new antiretroviral drugs for these miRNAs.