Reassessing APOBEC3G Inhibition by HIV-1 Vif-Derived Peptides

Overview

Journal J Mol Biol

Publisher Elsevier

Specialties Microbiology
Molecular Biology

Date 2016 Nov 27

PMID 27887868

Citations 5

Authors

Christopher M Richards

Ming Li

Angela L Perkins

Anurag Rathore

Daniel A Harki

Reuben S Harris

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Design of Vif-Derived Peptide Inhibitors with Anti-HIV-1 Activity by Interrupting Vif-CBFβ Interaction.

Gai Y, Duan S, Wang S, Liu K, Yu X, Yang C Viruses. 2024; 16(4).

PMID: 38675833 PMC: 11053914. DOI: 10.3390/v16040490.

Direct inhibition of human APOBEC3 deaminases by HIV-1 Vif independent of the proteolysis pathway.

Kamba K, Wan L, Unzai S, Morishita R, Takaori-Kondo A, Nagata T Biophys J. 2023; 123(3):294-306.

PMID: 38115583 PMC: 10870137. DOI: 10.1016/j.bpj.2023.12.015.

Leveraging the therapeutic, biological, and self-assembling potential of peptides for the treatment of viral infections.

Monroe M, Wang H, Anderson C, Jia H, Flexner C, Cui H J Control Release. 2022; 348:1028-1049.

PMID: 35752254 PMC: 11022941. DOI: 10.1016/j.jconrel.2022.06.037.

Dendritic Cells, the Double Agent in the War Against HIV-1.

Martin-Moreno A, Munoz-Fernandez M Front Immunol. 2019; 10:2485.

PMID: 31708924 PMC: 6820366. DOI: 10.3389/fimmu.2019.02485.

APOBEC Enzymes as Targets for Virus and Cancer Therapy.

Olson M, Harris R, Harki D Cell Chem Biol. 2017; 25(1):36-49.

PMID: 29153851 PMC: 5775913. DOI: 10.1016/j.chembiol.2017.10.007.

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