Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
J Virol. 2023 Dec 21;97(12):e0117923. doi: 10.1128/jvi.01179-23. Epub 2023 Nov 22.
The traditional view of retrovirus assembly posits that packaging of gRNA by HIV-1 Gag occurs in the cytoplasm or at the plasma membrane. However, our previous studies showing that HIV-1 Gag enters the nucleus and binds to USvRNA at transcription sites suggest that gRNA selection may occur in the nucleus. In the present study, we observed that HIV-1 Gag trafficked to the nucleus and co-localized with USvRNA within 8 hours of expression. In infected T cells (J-Lat 10.6) reactivated from latency and in a HeLa cell line stably expressing an inducible Rev-dependent HIV-1 construct, we found that Gag preferentially localized with euchromatin histone marks associated with enhancer and promoter regions near the nuclear periphery, which is the favored site HIV-1 integration. These observations support the innovative hypothesis that HIV-1 Gag associates with euchromatin-associated histones to localize to active transcription sites, promoting capture of newly synthesized gRNA for packaging.
传统的逆转录病毒组装观点认为，HIV-1 Gag 对 gRNA 的包装发生在细胞质或质膜中。然而，我们之前的研究表明，HIV-1 Gag 进入细胞核并与转录位点的 USvRNA 结合，这表明 gRNA 的选择可能发生在细胞核中。在本研究中，我们观察到 HIV-1 Gag 在表达后 8 小时内转运到细胞核并与 USvRNA 共定位。在从潜伏期重新激活的感染 T 细胞（J-Lat 10.6）和稳定表达诱导型 Rev 依赖性 HIV-1 构建体的 HeLa 细胞系中，我们发现 Gag 优先与靠近核周的增强子和启动子区域相关的常染色质组蛋白标记共定位，这是 HIV-1 整合的首选位点。这些观察结果支持了一个创新的假说，即 HIV-1 Gag 与常染色质相关的组蛋白结合，定位到活跃的转录位点，促进新合成的 gRNA 的捕获和包装。
