A macaque model of HIV-1 infection
A macaque model of HIV-1 infection
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DOI：
10.1073/pnas.0812587106
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发表时间：
2009-03-17
影响因子：
11.1
通讯作者：
Bieniasz, Paul D.
中科院分区：
文献类型：
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作者：
Hatziioannou, Theodora;Ambrose, Zandrea;Bieniasz, Paul D.
缺乏使用HIV-1作为挑战病毒的灵长类模型是艾滋病研究的障碍；现有模型通常使用与HIV-1不同的猿类病毒，降低了它们在临床前研究中的有效性。基于对灵长类动物TRIM5和APOBEC3抗逆转录病毒基因物种特异性变异的了解，我们构建了仅在vif基因上与HIV-1不同的类人型(St)HIV-1毒株。我们证明了这种最小限度修饰的stHIV-1毒株能够在猪尾猕猴(Macaca Nomestrina)淋巴细胞中进行高水平的体外复制。重要的是，感染stHIV-1的猪尾猕猴会导致急性病毒血症，接近感染HIV-1的人的水平，并随后持续感染几个月。此后，stHIV-1的复制至少部分地由CD8+T细胞控制。我们展示了这种基于HIV-1的动物模型在化学预防实验中的潜在用途，表明在严格的高剂量stHIV-1挑战之后，常用的HIV-1治疗方案可以提供明显的灭菌保护，使其免受感染。
The lack of a primate model that utilizes HIV-1 as the challenge virus is an impediment to AIDS research; existing models generally employ simian viruses that are divergent from HIV-1, reducing their usefulness in preclinical investigations. Based on an understanding of species-specific variation in primate TRIM5 and APOBEC3 antiretroviral genes, we constructed simian-tropic (st) HIV-1 strains that differ from HIV-1 only in the vif gene. We demonstrate that such minimally modified stHIV-1 strains are capable of high levels of replication in vitro in pig-tailed macaque (Macaca nemestrina) lymphocytes. Importantly, infection of pig-tailed macaques with stHIV-1 results in acute viremia, approaching the levels observed in HIV-1-infected humans, and an ensuing persistent infection for several months. stHIV-1 replication was controlled thereafter, at least in part, by CD8+ T cells. We demonstrate the potential utility of this HIV-1-based animal model in a chemoprophylaxis experiment, by showing that a commonly used HIV-1 therapeutic regimen can provide apparently sterilizing protection from infection following a rigorous high-dose stHIV-1 challenge.