Reassessing APOBEC3G Inhibition by HIV-1 Vif-Derived Peptides

JOURNAL OF MOLECULAR BIOLOGY

卷:429

Article

Richards, Christopher M.^1,2  Li, Ming^1,2  Perkins, Angela L.³  Rathore, Anurag¹  Harki, Daniel A.³  Harris, Reuben S.^1,2,4 

[1] Univ Minnesota, Dept Biochem Mol Biol & Biophys, 321 Church St SE, Minneapolis, MN 55455 USA

[2] Univ Minnesota, Inst Mol Virol, 515 Delaware St SE, Minneapolis, MN 55455 USA

[3] Univ Minnesota, Dept Med Chem, 2231 6th St SE, Minneapolis, MN 55455 USA

[4] Univ Minnesota, Howard Hughes Med Inst, 2231 6th St SE, Minneapolis, MN 55455 USA

关键词: DNA cytosine deamination;    Evolvability;    HIV-1;    Mutation;    Vif-derived peptides;   

DOI  :  10.1016/j.jmb.2016.11.012

来源: Elsevier

【 摘 要 】

The human APOBEC3G (A3G) enzyme restricts HIV-1 in the absence of the viral accessory protein viral infectivity factor (Vif) by deaminating viral cDNA cytosines to uracils. These uracil lesions base-pair with adenines during the completion of reverse transcription and result in A3G signature G-to-A mutations in the viral genome. Vif protects HIV-1 from A3G-mediated restriction by forming an E3-ubiquitin ligase complex to polyubiquitinate A3G and trigger its degradation. Prior studies indicated that Vif may also directly block the enzymatic activity of A3G and, provocatively, that Vif-derived peptides, Vif 25-39 and Vif 105-119, are similarly inhibitory. Here, we show that Vif 25-39 does not inhibit A3G enzymatic activity and that the inhibitory effect of Vif 105-119 and that of a shorter derivative Vif 107-115, although recapitulated, are non-specific. We also elaborate a simple method for assaying DNA cytosine deaminase activity that eliminates potential polymerase chain reaction-induced biases. Our results show that these Vif-derived peptides are unlikely to be useful as tools to study A3G function or as leads for the development of future therapeutics. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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