Coassembly and complementation of Gag proteins from HIV-1 and HIV-2, two distinct human pathogens
Coassembly and complementation of Gag proteins from HIV-1 and HIV-2, two distinct human pathogens
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DOI：
10.1016/j.molcel.2006.05.028
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发表时间：
2006-07-21
期刊：
影响因子：
16
通讯作者：
Hu, Wei-Shau
中科院分区：
文献类型：
--
作者：
Boyko, Vitaly;Leavitt, Maria;Hu, Wei-Shau
世界上大约有100万人同时感染艾滋病毒-1和艾滋病毒-2。为了确定这两种人类病原体之间的潜在相互作用，我们研究了HIV-1和HIV-2 Gag蛋白是否可以共同组装并在功能上相互补充。我们生成了Gag突变的基于HIV-1和hiv -2的载体；与野生型载体相比，这些突变体的病毒滴度急剧降低。HIV-1和HIV-2 Gag突变体的共表达可产生感染性病毒；此外，在某些组合中，异源互补表现出与同源互补相似的效率。此外，我们使用双分子荧光互补分析直接证明HIV-1和HIV-2 Gag可以相互作用和共同组装。综上所述，我们的研究结果表明HIV-1和HIV-2 Gag多蛋白在病毒复制过程中可以共同组装并在功能上相互补充；据我们所知，这是第一次这样的演示。这些研究对艾滋病的治疗和灵长类慢病毒的进化具有重要意义。
Approximately one million people in the world are dually infected with both HIV-1 and HIV-2. To identity potential interactions between these two human pathogens, we examined whether HIV-1 and HIV-2 Gag proteins can coassemble and functionally complement each other. We generated HIV-1 - and HIV-2-based vectors with mutations in Gag; compared with wild-type vectors, these mutants had drastically decreased viral titers. Coexpression of the mutant HIV-1 and HIV-2 Gag could generate infectious viruses; furthermore, heterologous complementation in certain combinations showed efficiency similar to homologous complementation. Additionally, we used bimolecularfluorescence complementation analysis to directly demonstrate that HIV-1 and HIV-2 Gag can interact and coassemble. Taken together, our results indicate that HIV-1 and HIV-2 Gag polyproteins can coassemble and functionally complement each other during virus replication; to our knowledge, this is the first demonstration of its kind. These studies have important implications for AIDS treatment and the evolution of primate lentiviruses.