Achuthan Vasudevan, Perreira Jill M, Ahn Jenny J, Brass Abraham L, Engelman Alan N
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215.
Department of Medicine, Harvard Medical School, Boston, MA 02115.
J Life Sci (Westlake Village). 2019 Jun;1(1):39-45. doi: 10.36069/jols/20190604.
HIV-1 integration favors active chromatin, which is primarily mediated through interactions between the viral capsid and integrase proteins with host factors cleavage and polyadenylation specificity factor 6 (CPSF6) and lens epithelium-derived growth factor/p75, respectively. Previously published image-based studies had suggested that HIV-1 prefers to integrate into chromatin that associates spatially with the nuclear periphery. Here, we re-evaluated previously reported HIV-1 nuclear distance measures across studies and show that HIV-1 prefers peri-nuclear and mid-nuclear zones similarly, with a common preference between studies mapping to the boundary between these two radial areas. We also discuss emerging roles for the capsid-CPSF6 interaction in facilitating HIV-1 pre-integration complex nuclear import and subsequent intranuclear trafficking to preferred sites of viral DNA integration.
HIV-1整合倾向于活跃染色质，这主要是通过病毒衣壳和整合酶蛋白分别与宿主因子切割和聚腺苷酸化特异性因子6（CPSF6）以及晶状体上皮衍生生长因子/p75之间的相互作用介导的。先前发表的基于图像的研究表明，HIV-1更喜欢整合到在空间上与核周相关的染色质中。在这里，我们重新评估了先前报道的跨研究的HIV-1核距离测量结果，并表明HIV-1同样更喜欢核周和核中区，不同研究之间的共同偏好映射到这两个径向区域之间的边界。我们还讨论了衣壳-CPSF6相互作用在促进HIV-1整合前复合物核输入以及随后在核内运输到病毒DNA整合的首选位点方面的新作用。
