Polymorphisms of the cytidine deaminase APOBEC3F have different HIV-1 restriction efficiencies

• Published in: Virology (New York, N.Y.) Vol. 527; pp. 21 - 31
• Main Authors: Mohammadzadeh, Nazanin, Follack, Tyson B., Love, Robin P., Stewart, Kris, Sanche, Stephen, Chelico, Linda
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.01.2019
• Subjects: APOBEC3; Deamination; HIV-1; Infectivity; Mutagenesis; Restriction factors; Vif; HIV-1; APOBEC3; Vif; Deamination; Mutagenesis; Infectivity; Restriction factors
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2018.11.004

The APOBEC3 enzyme family are host restriction factors that induce mutagenesis of HIV-1 proviral genomes through the deamination of cytosine to form uracil in nascent single-stranded (-)DNA. HIV-1 suppresses APOBEC3 activity through the HIV-1 protein Vif that induces APOBEC3 degradation. Here we compared two common polymorphisms of APOBEC3F. We found that although both polymorphisms have HIV-1 restriction activity, APOBEC3F 108 A/231V can restrict HIV-1 ΔVif up to 4-fold more than APOBEC3F 108 S/231I and is partially protected from Vif-mediated degradation. This resulted from higher levels of steady state expression of APOBEC3F 108 A/231 V. Individuals are commonly heterozygous for the APOBEC3F polymorphisms and these polymorphisms formed in cells, independent of RNA, hetero-oligomers between each other and with APOBEC3G. Hetero-oligomerization with APOBEC3F 108 A/231V resulted in partial stabilization of APOBEC3F 108 S/231I and APOBEC3G in the presence of Vif. These data demonstrate functional outcomes of APOBEC3 polymorphisms and hetero-oligomerization that affect HIV-1 restriction. •APOBEC3F 231V is more stable than APOBEC3F 231I in cells.•APOBEC3F 231V is more highly encapsidated into HIV-1 virions than APOBEC3F 231I.•APOBEC3F 231V and 231I occur as heterozygous alleles and the proteins interact in cells.•The coexpression of these APOBEC3Fs results in enhanced levels of HIV-1 mutagenesis.