热休克蛋白 90AB1 和高热挽救缺陷核心 HIV 的感染性。
Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores.
机构信息
Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA 94110, USA.
出版信息
Virology. 2013 Feb 5;436(1):162-72. doi: 10.1016/j.virol.2012.11.005. Epub 2012 Nov 30.
We previously showed that reduced infectivity of HIV with incompletely processed capsid-spacer protein 1 (CA-SP1) is rescued by cellular activation or increased expression of HSP90AB1, a member of the cytosolic heat shock protein 90 family. Here we show that HSP90AB1 is present in HIV virions and that HSP90AB1, but not nonfunctional mutated HSP90AB1(E42A+D88A), restores infectivity to HIV with mutations in CA that alter core stability. Further, the CA mutants were hypersensitive to pharmacological inhibition of HSP90AB1. In agreement with Roesch et al. (2012), we found that culturing HIV at 39.5°C enhanced viral infectivity up to 30-fold in human peripheral blood mononuclear cells (p=0.002) and rescued CA-mutant infectivity in nonactivated cells, concurrent with elevated expression of HSP90AB1 during hyperthermia. In sum, the transdominant effect of HSP90AB1 on CA-mutant HIV infectivity suggests a potential role for this class of cellular chaperones in HIV core stability and uncoating.
我们之前曾表明，不完全加工的衣壳-间隔蛋白 1（CA-SP1）的 HIV 传染性降低可通过细胞激活或细胞溶质热休克蛋白 90 家族成员 HSP90AB1 的表达增加得到挽救。在这里，我们表明 HSP90AB1 存在于 HIV 病毒粒子中，并且 HSP90AB1（而非无功能的突变 HSP90AB1（E42A+D88A））可恢复改变核心稳定性的 CA 突变的 HIV 的感染性。此外，CA 突变体对 HSP90AB1 的药理学抑制作用更加敏感。与 Roesch 等人（2012 年）的研究结果一致，我们发现，在人类外周血单核细胞中，将 HIV 培养在 39.5°C 下可将病毒感染性提高多达 30 倍（p=0.002），并在未激活的细胞中挽救 CA 突变体的感染性，同时伴随着 HSP90AB1 在高温下的表达升高。总之，HSP90AB1 对 CA 突变 HIV 感染性的转显性作用表明该类细胞伴侣在 HIV 核心稳定性和脱壳中可能具有作用。
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