PDF(Pubmed)
Abstract：
HIV-1 is a highly host-specific retrovirus that infects humans but not most nonhuman primates. Thus, the lack of a suitable primate model that can be directly infected with HIV-1 hinders HIV-1/AIDS research. In the previous study, we have found that the northern pig-tailed macaques (NPMs) are susceptible to HIV-1 infection but show a nonpathogenic state. In this study, to understand this macaque-HIV-1 interaction, we assembled a de novo genome and longitudinal transcriptome for this species during the course of HIV-1 infection. Using comparative genomic analysis, a positively selected gene, Toll-like receptor 8, was identified with a weak ability to induce an inflammatory response in this macaque. In addition, an interferon-stimulated gene, interferon alpha inducible protein 27, was upregulated in acute HIV-1 infection and acquired an enhanced ability to inhibit HIV-1 replication compared with its human ortholog. These findings coincide with the observation of persistently downregulated immune activation and low viral replication and can partially explain the AIDS-free state in this macaque following HIV-1 infection. This study identified a number of unexplored host genes that may hamper HIV-1 replication and pathogenicity in NPMs and provided new insights into the host defense mechanisms in cross-species infection of HIV-1. This work will facilitate the adoption of NPM as a feasible animal model for HIV-1/AIDS research.
摘要：
HIV-1是一种高度宿主特异性的逆转录病毒，可感染人类，但不会感染大多数非人类灵长类动物。因此，缺乏合适的可直接感染HIV-1的灵长类动物模型阻碍了HIV-1/AIDS的研究。在之前的研究中,我们发现北方猪尾猕猴(NPM)对HIV-1感染易感,但表现为非致病状态.在这项研究中,为了理解这种猕猴与HIV-1的相互作用，在HIV-1感染过程中，我们为该物种组装了从头基因组和纵向转录组。使用比较基因组分析，一个积极选择的基因，Toll样受体8(TLR8),被鉴定为在该猕猴中诱导炎症反应的能力弱。此外,IFN刺激的基因，干扰素α诱导蛋白27（IFI27），与人类直系同源物相比，在急性HIV-1感染中上调，并获得了增强的抑制HIV-1复制的能力。这些发现与持续下调的免疫激活和低病毒复制的观察结果相吻合，并且可以部分解释该猕猴在HIV-1感染后的无艾滋病状态。这项研究确定了许多未开发的宿主基因，这些基因可能会阻碍NPM中HIV-1的复制和致病性，并为跨物种感染HIV-1的宿主防御机制提供了新的见解。这项工作将有助于采用NPM作为HIV-1/AIDS研究的可行动物模型。
