An aurora kinase-dependent role for Vif in regulating HIV-1-induced cell-cell fusion

Viral infectivity factor (Vif) is an HIV-1 accessory protein known for its counteraction of APOBEC3 enzymes. Vif has recently been shown to degrade PPP2R5A-E, leading to phosphoproteome remodeling and Aurora Kinase activation. This study explores Vif’s role in suppressing Env-mediated cell-cell fusion at the virological synapse. Using split NanoLuc-based cell-cell fusion assays, we confirm increased fusion in Vif-null virus and upon Aurora kinase inhibition. Notably, we find that Vif deletion significantly blunts the impact of Aurora kinase inhibition on cell-cell fusion, supporting our hypothesis that Vif-mediated regulation of cell-cell fusion depends on Aurora kinase signaling dysregulation, through PPP2R5A-E degradation.