Stremlau Matthew, Perron Michel, Lee Mark, Li Yuan, Song Byeongwoon, Javanbakht Hassan, Diaz-Griffero Felipe, Anderson Donovan J, Sundquist Wesley I, Sodroski Joseph
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School Division of AIDS, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5514-9. doi: 10.1073/pnas.0509996103. Epub 2006 Mar 15.
The host restriction factor TRIM5alpha mediates species-specific, early blocks to retrovirus infection; susceptibility to these blocks is determined by viral capsid sequences. Here we demonstrate that TRIM5alpha variants from Old World monkeys specifically associate with the HIV type 1 (HIV-1) capsid and that this interaction depends on the TRIM5alpha B30.2 domain. Human and New World monkey TRIM5alpha proteins associated less efficiently with the HIV-1 capsid, accounting for the lack of restriction in cells of these species. After infection, the expression of a restricting TRIM5alpha in the target cells correlated with a decrease in the amount of particulate capsid in the cytosol. In some cases, this loss of particulate capsid was accompanied by a detectable increase in soluble capsid protein. Inhibiting the proteasome did not abrogate restriction. Thus, TRIM5alpha restricts retroviral infection by specifically recognizing the capsid and promoting its rapid, premature disassembly.
宿主限制因子TRIM5α介导对逆转录病毒感染的物种特异性早期阻断；对这些阻断的易感性由病毒衣壳序列决定。在此，我们证明来自旧世界猴的TRIM5α变体与1型人类免疫缺陷病毒（HIV-1）衣壳特异性结合，且这种相互作用依赖于TRIM5α的B30.2结构域。人类和新世界猴的TRIM5α蛋白与HIV-1衣壳的结合效率较低，这解释了这些物种的细胞中缺乏限制作用的原因。感染后，靶细胞中具有限制作用的TRIM5α的表达与胞质中颗粒状衣壳数量的减少相关。在某些情况下，这种颗粒状衣壳的减少伴随着可溶性衣壳蛋白的可检测增加。抑制蛋白酶体并不能消除限制作用。因此，TRIM5α通过特异性识别衣壳并促进其快速、过早解体来限制逆转录病毒感染。
