Host AKT-mediated phosphorylation of HIV-1 accessory protein Vif potentiates infectivity via enhanced degradation of the restriction factor APOBEC3G

• DOI: 10.1016/j.jbc.2022.101805
• Publication Date: 2022-03-05T15:49:09Z
• Authors: Rameez Raja; Chenyao Wang; Ritu Mishra; Arundhoti Das; Amjad Ali; Akhil C. Banerjea
• Keywords: APOBEC3G

HIV-1 encodes accessory proteins that neutralize antiviral restriction factors to ensure its successful replication. One protein, the viral infectivity factor (Vif), is known promote ubiquitination and proteasomal degradation of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G), a cytosine deaminase leads hypermutations in DNA subsequent aberrant We have previously demonstrated transcription mediator Tat activates host progrowth PI-3-AKT pathway, which turn promotes Because Vif protein contains putative AKT phosphorylation motif RMRINT, here we investigated whether directly phosphorylates regulate function. Coimmunoprecipitation experiments showed interact with each other, supporting this hypothesis. Using vitro kinase assays, further at threonine 20, stability, as becomes destabilized after residue mutated alanine. Moreover, expression dominant-negative kinase-deficient well treatment chemical inhibitor increased K48-ubiquitination Vif. In contrast, constitutively active (Myr-AKT) reduced stability. Finally, inhibition function restored APOBEC3G levels, subsequently infectivity. Thus, our results establish novel mechanism stabilization through AKT-mediated reduces levels potentiates