Genomic evidence for the nonpathogenic state in HIV-1-infected northern pig-tailed macaques.
Wei PangYong ShaoXiao-Lin ZhuangYing LuWen-Qiang HeHong-Yi ZhengRong XinMing-Xu ZhangXiao-Liang ZhangJia-Hao SongRen-Rong TianFan ShenYi-Hui LiZu-Jiang ZhaoDong-Dong WuTian-Zhang SongPublished in: Molecular biology and evolution (2023)
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 shows 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 (TLR8), was identified with a weak ability to induce an inflammatory response in this macaque. In addition, an IFN-stimulated gene, interferon alpha inducible protein 27 (IFI27), 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.
Keyphrases
- antiretroviral therapy
- hiv aids
- hiv infected
- hiv positive
- human immunodeficiency virus
- toll like receptor
- inflammatory response
- genome wide
- immune response
- copy number
- liver failure
- dendritic cells
- hiv testing
- dna methylation
- nuclear factor
- rna seq
- men who have sex with men
- endothelial cells
- hepatitis c virus
- extracorporeal membrane oxygenation
- cross sectional
- respiratory failure
- drug induced