Disruption of human TRIM5α antiviral activity by nonhuman primate orthologues
Disruption of human TRIM5α antiviral activity by nonhuman primate orthologues
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DOI：
10.1128/jvi.79.12.7883-7888.2005
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发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Luban, J
中科院分区：
文献类型：
--
作者：
Berthoux, L;Sebastian, S;Luban, J
TRIM5是携带特定衣壳的逆转录病毒感染易感性的特定物种差异的决定因素。人类免疫缺陷病毒1型(HIV-1)感染被猕猴TRIN15的α亚型(TRIM5α(Rh))或猫头猴TRIX15-亲环素A基因融合的产物(TRIMCyp)阻断。人类TRIM5α能有效地限制特定的小鼠白血病病毒株(N-MLV)，但对HIV-1只有轻微的影响。TRIM5同源基因的氨基末端高度保守，具有促进同源多聚化的卷曲结构域。在这里，我们证明了TRIM5α(Rh)或TRIMCyp在人细胞中的异源表达干扰了内源性人TRIM5α(TRIM5α(Hu).)的抗N-MLV活性。从TRIMCyp中删除亲环素结构域不会影响异源多聚体或与TRIX15α(HU)的共定位，但会阻止干扰抗N-MLV的活性。这些数据表明，TRIM5同源物形成异多聚体，并表明C-末端延伸通过这些蛋白质的多聚体改变病毒识别。
TRIM5 is a determinant of species-specific differences in susceptibility to infection by retroviruses bearing particular capsids. Human immunodeficiency virus type 1 (HIV-1) infection is blocked by the alpha isoform of macaque TRIN15 (TRIM5 alpha(rh)) or by the product of the owl monkey TRIX15-cyclophilin A gene fusion (TRIMCyp). Human TRIM5 alpha potently restricts specific strains of murine leukemia virus (N-MLV) but has only a modest effect on HIV-1. The amino termini of TRIM5 orthologues are highly conserved and possess a coiled-coil domain that promotes homomultimerization. Here we show that heterologous expression of TRIM5 alpha(rh) or TRIMCyp in human cells interferes with the anti-N-MLV activity of endogenous human TRIM5 alpha (TRIM5 alpha(hu).). Deletion of the cyclophilin domain from TRIMCyp has no effect on heteromultimerization or colocalization with TRIX15 alpha(hu) but prevents interference with anti-N-MLV activity. These data demonstrate that TRIM5 orthologues form heteromultimers and indicate that C-terminal extensions alter virus recognition by multimers of these proteins.