Variable Prevalence and Functional Diversity of the Antiretroviral Restriction Factor TRIMCyp in Macaca fascicularis
Variable Prevalence and Functional Diversity of the Antiretroviral Restriction Factor TRIMCyp in Macaca fascicularis
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DOI：
10.1128/jvi.00097-11
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发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Hu, Shiu-Lok
中科院分区：
文献类型：
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作者：
Dietrich, Elizabeth A.;Brennan, Greg;Hu, Shiu-Lok
逆转录病毒限制因子TRIMCyp源自TRIM5基因，在进入后的步骤中阻止复制。到目前为止，已在四种亚洲猕猴身上发现了TrIMCyp，这四种猕猴是：短束猕猴、短尾短尾猴、短尾短尾猴和短尾猴。束支原体通常被用作艾滋病研究的模型，但TIMCyp在该物种中尚未被详细分析。我们分析了来自印度尼西亚、印度支那、菲律宾和毛里求斯的样本中TRIMCyp的流行情况。我们发现，TRIMCyp在印度尼西亚猕猴中的出现频率高于印度支那支原体猕猴，在菲律宾的样本中也存在。在毛里求斯束支原体猕猴中不存在TRIMCyp。然后，我们分析了来自印度尼西亚的三种动物来源的TRIMCyp的限制性内切酶特异性。一种等位基因，就像为Mulatta和M.nomestrina描述的原型TrIMCyp等位基因一样，限制了人类免疫缺陷病毒2型(HIV-2)和猫科免疫缺陷病毒(FIV)，但不限制HIV-1。其他的限制HIV-1和FIV，但不限制HIV-2。突变研究证实，TrIMCyp的氨基酸残基369和446位的多态(或亲环素A[CypA]区域的66位和143位)赋予限制性专一性。此外，我们还发现了卷曲螺旋结构域中的一个多态，它似乎影响了TRIMCyp的表达或稳定性。综上所述，这些数据表明，束支原体拥有迄今为止在任何灵长类物种中描述的最多样化的TRIM5限制因子阵列。这些发现与我们理解逆转录病毒限制因子的进化以及在艾滋病研究中使用束支原体模型有关。
The retroviral restriction factor TRIMCyp, derived from the TRIM5 gene, blocks replication at a postentry step. TRIMCyp has so far been found in four species of Asian macaques, Macaca fascicularis, M. mulatta, M. nemestrina, and M. leonina. M. fascicularis is commonly used as a model for AIDS research, but TRIMCyp has not been analyzed in detail in this species. We analyzed the prevalence of TRIMCyp in samples from Indonesia, Indochina, the Philippines, and Mauritius. We found that TRIMCyp is present at a higher frequency in Indonesian than in Indochinese M. fascicularis macaques and is also present in samples from the Philippines. TRIMCyp is absent in Mauritian M. fascicularis macaques. We then analyzed the restriction specificity of TRIMCyp derived from three animals of Indonesian origin. One allele, like the prototypic TRIMCyp alleles described for M. mulatta and M. nemestrina, restricts human immunodeficiency virus type 2 (HIV-2) and feline immunodeficiency virus (FIV) but not HIV-1. The others restrict HIV-1 and FIV but not HIV-2. Mutagenesis studies confirmed that polymorphisms at amino acid residues 369 and 446 in TRIMCyp (or residues 66 and 143 in the cyclophilin A [CypA] domain) confer restriction specificity. Additionally, we identified a polymorphism in the coiled-coil domain that appears to affect TRIMCyp expression or stability. Taken together, these data show that M. fascicularis has the most diverse array of TRIM5 restriction factors described for any primate species to date. These findings are relevant to our understanding of the evolution of retroviral restriction factors and the use of M. fascicularis models in AIDS research.