AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan; The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, Japan.
Virology. 2019 Jun;532:97-107. doi: 10.1016/j.virol.2019.04.013. Epub 2019 Apr 27.
The matrix (MA) domain of HIV-1 Gag directs membrane binding of the Gag precursor polyprotein during the late events of virus replication. However, the effects of alteration in Gag membrane binding early post-infection are not well understood. To investigate impacts of MA mutations that alter Gag membrane binding on the phenotypes of newly produced virus particles, we extensively characterized two MA mutants by virological, biochemical, and morphological approaches. The V6R mutation, which decreases Gag membrane binding, modified Gag processing and core morphogenesis and impaired core uncoating, reverse transcription, and viral DNA integration. On the other hand, the L20K mutation, which increases Gag membrane binding, primarily decreased integrated DNA levels without affecting the viral components and morphology. These data suggest that HIV-1 MA plays roles in functional core formation and the following post-entry steps of the virus replication cycle. (140/150 words).
HIV-1 Gag 的基质 (MA) 结构域在病毒复制的晚期指导 Gag 前体多蛋白与膜的结合。然而,在感染后早期改变 Gag 与膜的结合对新产生的病毒粒子表型的影响还不是很清楚。为了研究改变 Gag 与膜结合的 MA 突变对新产生的病毒粒子的表型的影响,我们通过病毒学、生化和形态学方法对两种 MA 突变体进行了广泛的特征分析。降低 Gag 与膜结合的 V6R 突变改变了 Gag 的加工和核心形态发生,并损害了核心脱壳、逆转录和病毒 DNA 整合。另一方面,增加 Gag 与膜结合的 L20K 突变主要降低了整合 DNA 的水平,而不影响病毒成分和形态。这些数据表明,HIV-1 MA 在功能性核心形成和病毒复制周期的后续进入步骤中发挥作用。(140/150 字)。