Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest

Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest

Blog Article

The seminal description of the cellular restriction factor APOBEC3G and its antagonism by HIV-1 Vif has underpinned two decades of research on the host-virus interaction.We recently reported that HIV-1 Vif is also able to degrade the PPP2R5 family of regulatory subunits of key cellular phosphatase PP2A (PPP2R5A-E; Greenwood et al., 2016; Naamati et al., 2019).

We now identify amino acid polymorphisms at positions 31 and 128 of a&d ej-123 HIV-1 Vif which selectively regulate the degradation of PPP2R5 family proteins.These residues covary across HIV-1 viruses in vivo, favouring depletion of PPP2R5A-E.Through analysis of point mutants and naturally occurring Vif variants, we further show that degradation of PPP2R5 family subunits is both necessary and sufficient for Vif-dependent G2/M cell cycle arrest.Antagonism of PP2A by HIV-1 Vif is therefore independent of APOBEC3 family proteins, and regulates cell bekindtopets.com cycle progression in HIV-infected cells.