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第1281回 HIV-1 adaptation studies reveal a novel Vif-independent mechanism for evading lethal restriction by APOBEC3G
2018年 2月27日 (火) 16:00〜17:00
Terumasa Ikeda博士 (HHMI Research Specialist, University of Minnesota)
HIV-1 adaptation studies reveal a novel Vif-independent mechanism for evading lethal restriction by APOBEC3G
HIV-1 replication requires Vif-mediated neutralization of APOBEC3 antiviral enzymes. Viruses lacking Vif succumb to deamination-dependent and -independent restriction processes. Here, HIV-1 adaptation studies are leveraged to ask whether viruses with an irreparable vif deletion could develop resistance to restrictive levels of APOBEC3G. Several resistant viruses were recovered with multiple amino acid substitutions in Env, and these changes alone are sufficient to protect Vif-null viruses from APOBEC3G-dependent restriction in T cell lines. Env adaptations cause decreased fusogenicity, which allows for higher levels of Gag-Pol packaging. Increased concentrations of packaged Pol in turn correlate with faster virus DNA replication and reduced APOBEC3G-mediated hypermutation of viral replication intermediates. Taken together, these studies reveal a novel Env- and Pol-dependent mechanism that HIV-1 can use to escape restriction. This mechanism may provide transmitting viruses with an additional layer of protection, and may also be relevant to other viruses that lack obvious Vif-like defense mechanisms.