Rohr Olivier, Marban Céline, Aunis Dominique, Schaeffer Evelyne
Institut National de la Santé Recherche Médicale Unité, Strasbourg, France.
J Leukoc Biol. 2003 Nov;74(5):736-49. doi: 10.1189/jlb.0403180. Epub 2003 Aug 11.
Transcription is a crucial step for human immunodeficiency virus type 1 (HIV-1) expression in all infected host cells, from T lymphocytes, thymocytes, monocytes, macrophages, and dendritic cells in the immune system up to microglial cells in the central nervous system. To maximize its replication, HIV-1 adapts transcription of its integrated proviral genome by ideally exploiting the specific cellular environment and by forcing cellular stimulatory events and impairing transcriptional inhibition. Multiple cell type-specific interplays between cellular and viral factors perform the challenge for the virus to leave latency and actively replicate in a great diversity of cells, despite the variability of its long terminal repeat region in different HIV strains. Knowledge about the molecular mechanisms underlying transcriptional regulatory events helps in the search for therapeutic agents that target the step of transcription in anti-HIV strategies.
转录是1型人类免疫缺陷病毒(HIV-1)在所有受感染宿主细胞中表达的关键步骤,这些细胞包括免疫系统中的T淋巴细胞、胸腺细胞、单核细胞、巨噬细胞和树突状细胞,直至中枢神经系统中的小胶质细胞。为了最大限度地进行复制,HIV-1通过理想地利用特定的细胞环境、促使细胞刺激事件发生以及削弱转录抑制来适应其整合前病毒基因组的转录。尽管不同HIV毒株的长末端重复区域存在变异性,但细胞因子和病毒因子之间多种细胞类型特异性的相互作用,使病毒面临着在多种细胞中脱离潜伏状态并积极复制的挑战。了解转录调控事件背后的分子机制有助于寻找在抗HIV策略中靶向转录步骤的治疗药物。