TRIM5α mediates the postentry block to N-tropic murine leukemia viruses in human cells
TRIM5α mediates the postentry block to N-tropic murine leukemia viruses in human cells
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DOI：
10.1073/pnas.0403364101
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发表时间：
2004-08-10
影响因子：
11.1
通讯作者：
Sodroski, J
中科院分区：
文献类型：
--
作者：
Perron, MJ;Stremlau, M;Sodroski, J
小鼠白血病病毒（MLV）根据其感染特定小鼠品系的能力分为N嗜性（N-MLV）或B嗜性（B-MLV）。N-MLV感染的早期阶段在几种哺乳动物物种（包括人类）的细胞中被阻断。这种阻断是由一种显性宿主因子介导的，该因子在病毒进入细胞后不久就靶向病毒衣壳。在恒河猴细胞中，与HIV-1类似的阻断作用是由TRIM 5 α介导的。在这里，我们表明，人类TRIM 5 α是必要的和足够的限制N-MLV在人类细胞。恒河猴TRIM 5 α可有效阻断HIV-1感染，但对N-MLV感染仅表现出中度抑制。B-MLV对人和恒河猴TRIM 5 α的抗病毒作用具有抗性，通过将B-MLV衣壳蛋白的残基110改变为N-MLV衣壳中发现的氨基酸，赋予了对TRIM 5 α介导的限制的敏感性。我们的研究结果表明，TRIM 5 α的物种特异性变异决定了其阻断不同逆转录病毒感染的能力。
Murine leukemia viruses (MLVs) have been classified as N-tropic (N-MLV) or B-tropic (B-MLV), depending on their ability to infect particular mouse strains. The early phase of N-MLV infection is blocked in the cells of several mammalian species, including humans. This block is mediated by a dominant host factor that targets the viral capsid soon after virus entry into the cell has been achieved. A similar block to HIV-1 in rhesus monkey cells is mediated by TRIM5alpha. Here we show that human TRIM5alpha is both necessary and sufficient for the restriction of N-MLV in human cells. Rhesus monkey TRIM5alpha, which potently blocks HIV-1 infection, exhibited only modest inhibition of N-MLV infection. B-MLV was resistant to the antiviral effects of both human and rhesus monkey TRIM5alpha susceptibility to TRIM5alpha-mediated restriction was conferred by alteration of residue 110 of the B-MLV capsid protein to the amino acid found in the N-MLV capsid. Our results demonstrate that species-specific variation in TRIM5alpha governs its ability to block infection by diverse retrovinuses.