Lewitus Eric, Li Yifan, Rolland Morgane
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr, Bethesda, MD 20817, USA.
Virus Evol. 2024 Dec 12;11(1):veae108. doi: 10.1093/ve/veae108. eCollection 2025.
HIV-1 Vif's principal function is to counter the antiretroviral activities of DNA-editing APOBEC3 cytidine deaminases. Unconstrained APOBEC3 activity introduces premature stop codons in HIV-1 genes and can lead to viral inactivation. To investigate the evolution and diversification of Vif over the HIV-1 pandemic and document evidence of APOBEC3-mediated pressure, we analyzed 4612 publicly available sequences derived from 10 dominant subtypes and circulating recombinant forms (CRFs) using the Hervé platform. We found widespread evidence of diversifying selection that was convergent across subtypes and CRFs, but remarkable stability in consensus sequences over time. Divergence and selection did not favor APOBEC3-interacting sites. We furthermore found that APOBEC3-induced substitutions in and genes increased over time and were positively associated with diversity. These results suggest that APOBEC3-driven adaptation in Vif is relatively rare and that permissiveness to human APOBEC3-induced substitution as a mechanism for generating diversity may be advantageous to HIV-1 evolution.
HIV-1病毒感染因子（Vif）的主要功能是对抗DNA编辑的载脂蛋白B mRNA编辑酶催化多肽样3（APOBEC3）胞苷脱氨酶的抗逆转录病毒活性。不受限制的APOBEC3活性会在HIV-1基因中引入过早的终止密码子，并可能导致病毒失活。为了研究Vif在整个HIV-1大流行过程中的进化和多样性，并记录APOBEC3介导的压力的证据，我们使用埃尔韦平台分析了来自10种主要亚型和循环重组形式（CRF）的4612条公开可用序列。我们发现了广泛的多样化选择证据，这种选择在各亚型和CRF中是趋同的，但随着时间的推移，共有序列具有显著的稳定性。分歧和选择并不有利于与APOBEC3相互作用的位点。我们还发现，随着时间的推移，APOBEC3诱导的在env和gag基因中的替换增加，并且与vif多样性呈正相关。这些结果表明，APOBEC3驱动的Vif适应性相对罕见，并且允许人类APOBEC3诱导的替换作为产生多样性的一种机制可能对HIV-1的进化有利。
