Multiple sites in the N-terminal half of simian immunodeficiency virus capsid protein contribute to evasion from rhesus monkey TRIM5α-mediated restriction.
Multiple sites in the N-terminal half of simian immunodeficiency virus capsid protein contribute to evasion from rhesus monkey TRIM5α-mediated restriction.
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DOI：
10.1186/1742-4690-7-72
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发表时间：
2010-09-08
期刊：
影响因子：
3.3
通讯作者：
Nakayama EE
中科院分区：
文献类型：
--
作者：
Kono K;Song H;Yokoyama M;Sato H;Shioda T;Nakayama EE
我们先前报道食蟹猴(CM)TRIM5α可以限制人类免疫缺陷病毒2型(HIV-2)衣壳蛋白(CA)第120位携带的Pro，但它不能限制含有谷氨酰胺或丙氨酸的HIV-2毒株。相反，恒河猴(Rh)trim5α可以限制所有测试的HIV-2毒株，但不能限制从猕猴分离的猴免疫缺陷病毒(SIVmac)，尽管它与HIV-2基因相似。我们试图利用SIVmac239和HIV-2GH123株之间形成的嵌合病毒来鉴定从Rh TRIM5α介导的限制中逃避SIVmac的病毒决定因素。与先前的研究一致，携带α-2CA的第4和第5(L4/5)(第82到第99个氨基酸残基)之间环的嵌合病毒被rh TRIM5α有效地限制。然而，SIVmac239CA相应的环(从第81位氨基酸到第97位氨基酸残基)不足以逃避HIV-2背景下的Rh TRIM5α限制。SIVmac239CA第118位氨基酸上的谷氨酰胺到脯氨酸的单一替换，对应于HIV-2GH123的第120位氨基酸，也增加了对Rh TRIM5α的易感性，这表明SIVmac239CA第118位的谷氨酰胺是逃避Rh TRIM5α所必需的。此外，SIVmac CA的α-螺旋6的N末端部分(第5~12个氨基酸残基)以及第107和109个氨基酸残基是完全逃避Rh TRIM5α介导的限制所必需的。六聚体GH123CA的三维模型表明，这多个区域位于CA表面，表明它们与TRIM5α直接相互作用。我们发现，SIVmac CA的多个区域是完全逃避Rh TRIM5α限制所必需的。
We previously reported that cynomolgus monkey (CM) TRIM5α could restrict human immunodeficiency virus type 2 (HIV-2) strains carrying a proline at the 120th position of the capsid protein (CA), but it failed to restrict those with a glutamine or an alanine. In contrast, rhesus monkey (Rh) TRIM5α could restrict all HIV-2 strains tested but not simian immunodeficiency virus isolated from macaque (SIVmac), despite its genetic similarity to HIV-2. We attempted to identify the viral determinant of SIVmac evasion from Rh TRIM5α-mediated restriction using chimeric viruses formed between SIVmac239 and HIV-2 GH123 strains. Consistent with a previous study, chimeric viruses carrying the loop between α-helices 4 and 5 (L4/5) (from the 82nd to 99th amino acid residues) of HIV-2 CA were efficiently restricted by Rh TRIM5α. However, the corresponding loop of SIVmac239 CA alone (from the 81st to 97th amino acid residues) was not sufficient to evade Rh TRIM5α restriction in the HIV-2 background. A single glutamine-to-proline substitution at the 118th amino acid of SIVmac239 CA, corresponding to the 120th amino acid of HIV-2 GH123, also increased susceptibility to Rh TRIM5α, indicating that glutamine at the 118th of SIVmac239 CA is necessary to evade Rh TRIM5α. In addition, the N-terminal portion (from the 5th to 12th amino acid residues) and the 107th and 109th amino acid residues in α-helix 6 of SIVmac CA are necessary for complete evasion from Rh TRIM5α-mediated restriction. A three-dimensional model of hexameric GH123 CA showed that these multiple regions are located on the CA surface, suggesting their direct interaction with TRIM5α. We found that multiple regions of the SIVmac CA are necessary for complete evasion from Rh TRIM5α restriction.
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影响因子：
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作者：
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通讯作者：
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10.1073/pnas.0505659102
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