人类免疫缺陷病毒 1 型整合酶 SUMOylation 的损伤与早期复制缺陷相关。
Impairment of human immunodeficiency virus type-1 integrase SUMOylation correlates with an early replication defect.
机构信息
CNRS UMR7212, INSERM U944, Institut Universitaire d'Hématologie-Université Paris7 Diderot, 75475 Paris, France.
出版信息
J Biol Chem. 2011 Jun 10;286(23):21013-22. doi: 10.1074/jbc.M110.189274. Epub 2011 Mar 21.
Abstract
HIV-1 integrase (IN) orchestrates the integration of the reverse transcribed viral cDNA into the host cell genome and participates also in other steps of HIV-1 replication. Cellular and viral factors assist IN in performing its multiple functions, and post-translational modifications contribute to modulate its activities. Here, we show that HIV-1 IN is modified by SUMO proteins and that phylogenetically conserved SUMOylation consensus motifs represent major SUMO acceptor sites. Viruses harboring SUMOylation site IN mutants displayed a replication defect that was mapped during the early stages of infection, before integration but after reverse transcription. Because SUMOylation-defective IN mutants retained WT catalytic activity, we hypothesize that SUMOylation might regulate the affinity of IN for co-factors, contributing to efficient HIV-1 replication.
摘要
HIV-1 整合酶（IN）协调逆转录病毒 cDNA 整合到宿主细胞基因组中，并且还参与 HIV-1 复制的其他步骤。细胞和病毒因子协助 IN 执行其多种功能，并且翻译后修饰有助于调节其活性。在这里，我们表明 HIV-1 IN 被 SUMO 蛋白修饰，并且系统发育上保守的 SUMO 化共识基序代表主要的 SUMO 接受位点。携带 SUMO 化 IN 突变体的病毒显示出复制缺陷，该缺陷在整合之前但在逆转录之后的感染早期阶段被定位。因为 SUMO 化缺陷型 IN 突变体保留了 WT 催化活性，所以我们假设 SUMO 化可能调节 IN 与共因子的亲和力，有助于 HIV-1 的有效复制。
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