Anderson Jenny L, Campbell Edward M, Figueiredo Anna, Hope Thomas J
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Ward 8-140, 303 East Chicago Avenue, Chicago, IL 60611, USA.
J Virol. 2008 Mar;82(5):2575-9. doi: 10.1128/JVI.00962-07. Epub 2007 Dec 12.
TRIM5alpha restriction factors protect target cells from retroviruses by blocking infection prior to the accumulation of viral reverse transcription (RT) products. Here, we demonstrate that heat shock perturbed owl monkey TRIMCyp and rhesus TRIM5alpha-mediated restriction of human immunodeficiency virus type 1 (HIV-1) late RT products and 2-long terminal repeat circles. Heat shock partially rescued HIV-1 infection from TRIMCyp restriction, and this rescue became more profound when combined with the presence of the proteasome inhibitor MG132. This indicates that viral RT products rescued from restriction by either heat shock treatment or the presence of MG132 are on a productive pathway, supporting a model in which TRIM5alpha proteins restrict retroviruses in multiple phases that are differentially sensitive to heat shock and proteasome inhibitors.
TRIM5α限制因子通过在病毒逆转录(RT)产物积累之前阻断感染来保护靶细胞免受逆转录病毒感染。在此,我们证明热休克扰乱了夜猴TRIMCyp和恒河猴TRIM5α介导的对1型人类免疫缺陷病毒(HIV-1)晚期RT产物和2-长末端重复序列环的限制。热休克部分挽救了TRIMCyp限制下的HIV-1感染,并且当与蛋白酶体抑制剂MG132同时存在时,这种挽救作用变得更加显著。这表明通过热休克处理或MG132的存在从限制中挽救的病毒RT产物处于生产性途径,支持了一种模型,即TRIM5α蛋白在对热休克和蛋白酶体抑制剂敏感性不同的多个阶段限制逆转录病毒。