Stevenson M, Brichacek B, Heinzinger N, Swindells S, Pirruccello S, Janoff E, Emerman M
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5120, USA.
Adv Exp Med Biol. 1995;374:33-45. doi: 10.1007/978-1-4615-1995-9_4.
Research is beginning to yield insight into determinants which govern cell cycle dependence of provirus establishment by the onco-retroviruses. In the case of HIV-1, nucleophilic components associated with the viral preintegration complex facilitate mitosis independent nuclear localization of viral DNA and provirus establishment. Differences in the metabolic activity between G0 T cells and macrophages, the two primary targets for HIV-1 infection, lead to significantly different outcomes with regards to provirus establishment following infection of these cells. Thus, macrophages appear fully permissive to productive HIV-1 replication while non-dividing (G0 T cells) restrict virus replication at a step which proceeds nuclear import of viral DNA. The requirement for T cell activation in productive HIV-1 replication has important implications for the relationship between immune activation and virus burden. It remains to be determined whether modulating the immune activation status of the infected individual may provide an opportunity for modulating virus burden and influencing disease course.
研究开始深入了解决定致癌逆转录病毒建立前病毒的细胞周期依赖性的因素。就HIV-1而言，与病毒整合前复合物相关的亲核成分促进病毒DNA的有丝分裂独立核定位和前病毒的建立。HIV-1感染的两个主要靶标G0 T细胞和巨噬细胞之间代谢活性的差异，导致这些细胞感染后在前病毒建立方面产生显著不同的结果。因此，巨噬细胞似乎完全允许HIV-1进行有效复制，而非分裂的（G0 T细胞）在病毒DNA核输入之前的步骤限制病毒复制。HIV-1有效复制中T细胞激活的需求对免疫激活与病毒载量之间的关系具有重要意义。调节受感染个体的免疫激活状态是否可能为调节病毒载量和影响疾病进程提供机会，仍有待确定。
