HIV-1 Vif disrupts phosphatase feedback regulation at the kinetochore, leading to a pronounced pseudo-metaphase arrest

• DOI: 10.7554/elife.101136.2
• Publication Date: 2025-02-07T17:25:15Z
• Authors: Dhaval Ghone; Edward L Evans; Madison Bandini; Kaelyn G Stephenson; Nathan M Sherer; Aussie Suzuki
• Keywords: Prometaphase; Spindle checkpoint

Virion Infectivity Factor (Vif) of the Human Immunodeficiency Virus type 1 (HIV-1) targets and degrades cellular APOBEC3 proteins, key regulators intrinsic innate antiretroviral immune responses, thereby facilitating HIV-1 infection. While Vif’s role in degrading APOBEC3G is well-studied, Vif also known to cause cell cycle arrest, but detailed nature effects on has yet be delineated. In this study, we employed high-temporal single-cell live imaging super-resolution microscopy monitor individual cells during Vif-induced arrest. Our findings reveal that does not affect G2/M boundary as previously thought. Instead, triggers a unique robust pseudo-metaphase distinct from mild prometaphase arrest induced by Vpr. During chromosomes align properly form metaphase plate, later lose alignment, resulting polar chromosomes. Notably, Vif, unlike Vpr, significantly reduces levels both Protein Phosphatase (PP1) 2A (PP2A) at kinetochores, which regulate chromosome-microtubule interactions. These results unveil novel for kinetochore regulation governs spatial organization mitosis.