Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication.
Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication.
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DOI：
10.1016/j.cell.2008.07.032
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发表时间：
2008-10-03
期刊：
影响因子：
64.5
通讯作者：
Chanda, Sumit K.
中科院分区：
文献类型：
--
作者：
Konig, Renate;Zhou, Yingyao;Elleder, Daniel;Diamond, Tracy L.;Bonamy, Ghislain M. C.;Irelan, Jeffrey T.;Chiang, Chih-Yuan;Tu, Buu P.;De Jesus, Paul D.;Lilley, Caroline E.;Seidel, Shannon;Opaluch, Amanda M.;Caldwell, Jeremy S.;Weitzman, Matthew D.;Kuhen, Kelli L.;Bandyopadhyay, Sourav;Ideker, Trey;Orth, Anthony P.;Miraglia, Loren J.;Bushman, Frederic D.;Young, John A.;Chanda, Sumit K.
人类免疫缺陷病毒（HIV-1和HIV-2）依赖于宿主编码的蛋白质来促进其复制。在这里，我们将全基因组siRNA分析与人类相互作用组数据库的询问相结合，以组装包含213种确认的宿主细胞因子和11种HIV-1编码蛋白的宿主-病原体生化网络。调节泛素结合、蛋白水解、DNA损伤反应和RNA剪接的蛋白复合物被鉴定为早期HIV-1感染的重要调节剂。此外，超过40种新的因子被证明特异性地影响HIV-1 DNA合成的起始和/或动力学，包括细胞骨架调节蛋白、翻译后修饰的调节剂和核酸结合蛋白。最后，15种具有不同功能作用的蛋白质，包括核转运、前列腺素合成、泛素化和转录，被发现影响核输入或病毒DNA整合。总之，这里描述的多尺度方法已经揭示了多蛋白病毒-宿主相互作用，这些相互作用可能协同作用以促进HIV-1感染的早期步骤。
Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA damage response and RNA splicing were identified as important modulators of early stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of post-translational modification, and nucleic acid binding proteins. Finally, fifteen proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multi-scale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate early steps of HIV-1 infection.
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影响因子：
11.4
作者：
Malki, S;Nef, S;Boizet-Bonhoure, B
通讯作者：
Boizet-Bonhoure, B
影响因子：
3.3
作者：
Griffis, ER;Craige, B;Powers, MA
通讯作者：
Powers, MA
影响因子：
3
作者：
Bader, GD;Hogue, CW
通讯作者：
Hogue, CW
影响因子：
5.4
作者：
Butler, SL;Johnson, EP;Bushman, FD
通讯作者：
Bushman, FD
DOI：
10.1073/pnas.0604320103
发表时间：
2006-10-03
影响因子：
11.1
作者：
Mukherji, Mridul;Bell, Russell;Schultz, Peter G.
通讯作者：
Schultz, Peter G.