CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Cell Host Microbe. 2015 Aug 12;18(2):233-42. doi: 10.1016/j.chom.2015.06.018. Epub 2015 Jul 23.
The correct ratio of the HIV-1 structural protein Gag to the envelope protein (Env) is important for maximal virion infectivity. How the virus ensures the production of Gag and Env proteins in an appropriate ratio remains unknown. We report that HIV-1 exploits the host factor RuvB-like 2 (RVB2) to balance relative expression of Gag and Env for efficient production of infectious virions. RVB2 inhibits Gag expression by interacting with both the encoded Matrix (MA) domain of Gag protein and 5' UTR of the translating mRNA and promoting mRNA degradation in a translation-dependent manner. This inhibitory activity of RVB2 is antagonized by Env through competitive interaction with MA, allowing Gag synthesis to proceed when Env levels are adequate for virion assembly. In HIV-1-positive patients, RVB2 levels positively correlate with viral loads and disease progression status. These findings reveal a mechanism by which HIV-1 regulates its protein expression.
HIV-1 结构蛋白 Gag 与包膜蛋白（Env）的正确比例对于最大病毒感染力非常重要。病毒如何确保 Gag 和 Env 蛋白以适当的比例产生仍不清楚。我们报告说，HIV-1 利用宿主因子 RuvB 样 2（RVB2）来平衡 Gag 和 Env 的相对表达，以有效地产生感染性病毒粒子。RVB2 通过与 Gag 蛋白编码的基质（MA）结构域和正在翻译的 mRNA 的 5'UTR 相互作用，以翻译依赖的方式促进 mRNA 降解，从而抑制 Gag 表达。Env 通过与 MA 的竞争性相互作用拮抗 RVB2 的这种抑制活性，从而允许在 Env 水平足以进行病毒组装时进行 Gag 合成。在 HIV-1 阳性患者中，RVB2 水平与病毒载量和疾病进展状况呈正相关。这些发现揭示了 HIV-1 调节其蛋白表达的一种机制。
