A dominant-negative effect of cynomolgus monkey tripartite motif protein TRIM5alpha on anti-simian immunodeficiency virus SIVmac activity of an African green monkey orthologue.
A dominant-negative effect of cynomolgus monkey tripartite motif protein TRIM5alpha on anti-simian immunodeficiency virus SIVmac activity of an African green monkey orthologue.
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DOI：
10.1016/j.virol.2006.03.035
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发表时间：
2006-06
期刊：
影响因子：
3.7
通讯作者：
E. Nakayama;Hikoichiro Maegawa;T. Shioda
中科院分区：
文献类型：
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作者：
E. Nakayama;Hikoichiro Maegawa;T. Shioda
非洲绿猴（AGM）三联基序蛋白（TRIM）5α可以抑制人类免疫缺陷病毒1型（HIV-1）和猿猴免疫缺陷病毒SIVmac，而食蟹猴（CM）TRIM5α可以抑制HIV-1，但不能抑制SIVmac。我们之前报道过 AGM TRIM5α 的 SPRY(B30.2) 结构域中的 17 个氨基酸区域和相邻的 20 个氨基酸重复决定了物种特异性。在本研究中，我们证明 CM TRIM5α 对 AGM TRIM5α 的抗 SIVmac 活性具有显性负效应。相比之下，缺乏 20 个氨基酸重复的突变 TRIM5α 不具有显性负效应，即使它们未能限制 SIVmac。这些结果表明，SPRY结构域的寡聚化是抗SIVmac活性所必需的，并且表明病毒衣壳与一个TRIM5α三聚体中的所有三个分子之间的紧密相互作用对于限制性活性可能不是必需的。
African green monkey (AGM) tripartite motif protein (TRIM) 5α can inhibit both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus SIVmac, whereas cynomolgus monkey (CM) TRIM5α can inhibit HIV-1, but not SIVmac. We previously reported that the 17-amino-acid region and an adjacent 20-amino-acid duplication in the SPRY(B30.2) domain of AGM TRIM5α determined the species specificity. In the present study, we demonstrated that CM TRIM5α had a dominant-negative effect on the anti-SIVmac activity of AGM TRIM5α. In contrast, mutant TRIM5αs lacking the 20-amino-acid duplication did not have the dominant-negative effect, even though they failed to restrict SIVmac. These results indicated that oligomerization of the SPRY domain is required for anti-SIVmac activity and suggest that tight interaction between the viral capsid and all three molecules in one TRIM5α trimer may not be necessary for restriction activity.