ESCRT-III 蛋白对 HIV-1 出芽的需求。
ESCRT-III protein requirements for HIV-1 budding.
机构信息
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA.
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA.
出版信息
Cell Host Microbe. 2011 Mar 17;9(3):235-242. doi: 10.1016/j.chom.2011.02.004.
Two early-acting components of the cellular ESCRT pathway, ESCRT-I and ALIX, participate directly in HIV-1 budding. The membrane fission activities of ESCRT-III subunits are also presumably required, but humans express 11 different CHMP/ESCRT-III proteins whose functional contributions are not yet clear. We therefore depleted cells of each of the different CHMP proteins and protein families and examined the effects on HIV-1 budding. Virus release was profoundly inhibited by codepletion of either CHMP2 or CHMP4 family members, resulting in ≥100-fold titer reductions. CHMP2A and CHMP4B proteins bound one another, and this interaction was required for budding. By contrast, virus release was reduced only modestly by depletion of CHMP3 and CHMP1 proteins (2- to 8-fold titer reductions) and was unaffected by depletion of other human ESCRT-III proteins. HIV-1 budding therefore requires only a subset of the known human ESCRT-III proteins, with the CHMP2 and CHMP4 families playing key functional roles.
细胞 ESCRT 途径的两个早期作用成分，ESCRT-I 和 ALIX，直接参与 HIV-1 的出芽。ESCRT-III 亚基的膜分裂活性也可能是必需的，但人类表达 11 种不同的 CHMP/ESCRT-III 蛋白，其功能贡献尚不清楚。因此，我们耗尽了不同的 CHMP 蛋白和蛋白家族的细胞，并检查了它们对 HIV-1 出芽的影响。CHMP2 或 CHMP4 家族成员的共耗竭严重抑制了病毒释放，导致滴度降低 100 倍以上。CHMP2A 和 CHMP4B 蛋白相互结合，这种相互作用是出芽所必需的。相比之下，CHMP3 和 CHMP1 蛋白的耗竭仅适度降低病毒释放（滴度降低 2-8 倍），而其他人类 ESCRT-III 蛋白的耗竭则没有影响。因此，HIV-1 出芽仅需要一组已知的人类 ESCRT-III 蛋白，其中 CHMP2 和 CHMP4 家族发挥关键功能作用。
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