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APOBEC3B Potently Restricts HIV-2 but Not HIV-1 in a Vif-Dependent Manner

Susana Bandarra, Eri Miyagi, Ana Clara Ribeiro, João Gonçalves, Klaus Strebel, Isabel Barahona

2021Journal of Virology11 citationsDOIOpen Access PDF

Abstract

-encoded protein functions primarily by targeting the APOBEC3 (A3) family of cytidine deaminases. All lentiviral Vif proteins have the ability to antagonize A3G; however, antagonizing other members of the A3 family is variable. Here, we report that HIV-2 Vif, unlike HIV-1 Vif, can induce degradation of A3B. Consequently, HIV-2 Vif but not HIV-1 Vif can inhibit the packaging of A3B. Interestingly, while A3B is packaged efficiently into the core of both HIV-1 and HIV-2 virions in the absence of Vif, it only affects the infectivity of HIV-2 particles. Thus, HIV-1 and HIV-2 have evolved two distinct mechanisms to antagonize the antiviral activity of A3B. Aside from its antiviral activity, A3B has been associated with mutations in some cancers. Degradation of A3B by HIV-2 Vif may be useful for cancer therapies.

Topics & Concepts

BiologyCytidine deaminaseGeneHEK 293 cellsGeneticsCell biologyMutationCytidineAdaptation (eye)Viral replicationENCODEViral proteinVirologyVirusCancer cellCell cultureImmunoprecipitationPhenotypeViral evolutionCellMutantPlasma protein bindingEndogenyMechanism (biology)CapsidGenomeCancerOncovirusProtein–protein interactionHost factorHost (biology)Regulation of gene expressionHIV Research and TreatmentVirus-based gene therapy researchHIV/AIDS drug development and treatment