Genomic Evidence for the Nonpathogenic State in HIV-1-Infected Northern Pig-Tailed Macaques.

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.

• Authors: Wei Pang, Yong Shao, Xiao-Lin Zhuang, Ying Lu, Wen-Qiang He, Hong-Yi Zheng, Rong Xin, Ming-Xu Zhang, Xiao-Liang Zhang, Jia-Hao Song, Ren-Rong Tian, Fan Shen, Yi-Hui Li, Zu-Jiang Zhao, Dong-Dong Wu, Yong-Tang Zheng
• Journal: Molecular biology and evolution (Mol Biol Evol) Vol. 40 Issue 5 (05 02 2023) ISSN: 1537-1719 [Electronic] United States
• PMID: 37134013 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.

Topics

• Animals
• Humans
• Macaca nemestrina
• HIV-1 (genetics)
• HIV Infections
• Genomics
• Simian Immunodeficiency Virus (genetics)