Dong Xinhong, Li Hua, Derdowski Aaron, Ding Lingmei, Burnett Atuhani, Chen Xuemin, Peters Timothy R, Dermody Terence S, Woodruff Elvin, Wang Jaang-Jiun, Spearman Paul
Department of Pediatrics and Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
Cell. 2005 Mar 11;120(5):663-74. doi: 10.1016/j.cell.2004.12.023.
Gag proteins direct the process of retroviral particle assembly and form the major protein constituents of the viral core. The matrix region of the HIV-1 Gag polyprotein plays a critical role in the transport of Gag to the plasma membrane assembly site. Recent evidence indicates that Gag trafficking to late endosomal compartments, including multivesicular bodies, occurs prior to viral particle budding from the plasma membrane. Here we demonstrate that the matrix region of HIV-1 Gag interacts directly with the delta subunit of the AP-3 complex, and that this interaction plays an important functional role in particle assembly. Disruption of this interaction eliminated Gag trafficking to multivesicular bodies and diminished HIV particle formation. These studies illuminate an early step in retroviral particle assembly and provide evidence that the trafficking of Gag to late endosomes is part of a productive particle assembly pathway.
Gag蛋白指导逆转录病毒颗粒的组装过程，并构成病毒核心的主要蛋白质成分。HIV-1 Gag多聚蛋白的基质区域在将Gag转运到质膜组装位点的过程中起着关键作用。最近的证据表明，在病毒颗粒从质膜出芽之前，Gag会转运到晚期内体区室，包括多泡体。在这里，我们证明HIV-1 Gag的基质区域与AP-3复合物的δ亚基直接相互作用，并且这种相互作用在颗粒组装中发挥重要的功能作用。这种相互作用的破坏消除了Gag向多泡体的转运，并减少了HIV颗粒的形成。这些研究阐明了逆转录病毒颗粒组装的早期步骤，并提供证据表明Gag向晚期内体的转运是生产性颗粒组装途径的一部分。
