Lei Ai-Hua, Zhang Gao-Hong, Tian Ren-Rong, Zhu Jia-Wu, Zheng Hong-Yi, Pang Wei, Zheng Yong-Tang
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Dongwuxue Yanjiu. 2014 May;35(3):186-95. doi: 10.11813/j.issn.0254-5853.2014.3.186.
The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 (HIV-1), which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-1NL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of vif-substituted HIV-1 (HSIV) in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-1SV chimeras, two HIV-1NL4-3-derived viruses encoding the viral infectivity factor (Vif) protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.
北方豚尾猕猴（Macaca leonina）已被鉴定为旧世界猴的一个独立物种，我们之前发现来自北方豚尾猕猴的外周血单核细胞（PBMCs）对1型人类免疫缺陷病毒（HIV-1）敏感，这可能是由于缺乏限制HIV-1复制的TRIM5蛋白。在此，我们研究了六种实验室适应的HIV-1毒株和三种原发性HIV-1分离株在北方豚尾猕猴PBMCs中的感染潜力。结果表明，这些毒株的特点是复制水平各异但较低，其中HIV-1NL4-3显示出最高的复制能力。基于限制因子载脂蛋白B mRNA编辑酶催化多肽样蛋白3（APOBEC3）与HIV/猴免疫缺陷病毒（SIV）衍生的病毒感染性因子（Vif）蛋白之间物种特异性相互作用的大量证据，我们随后检测了vif替代的HIV-1（HSIV）在北方豚尾猕猴PBMCs中的复制潜力。值得注意的是，HSIV-vifmac和stHIV-1SV嵌合体这两种源自HIV-1NL4-3、编码来自SIVmac239的Vif蛋白的病毒，在北方豚尾猕猴的细胞中能强劲复制，这表明HSIV能有效拮抗北方豚尾猕猴细胞中表达的APOBEC3蛋白的抗病毒活性。因此，我们的数据表明北方豚尾猕猴有潜力被开发成为一种有前景的人类艾滋病动物模型。
