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

Abstract:

: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.

journal_name

Virology

journal_title

Virology

authors

Mohammadzadeh N,Follack TB,Love RP,Stewart K,Sanche S,Chelico L

doi

10.1016/j.virol.2018.11.004

subject

Has Abstract

pub_date

2019-01-15 00:00:00

pages

21-31

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(18)30345-3

journal_volume

527

pub_type

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