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

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Marelli, Sara 
Williamson, James C 
Protasio, Anna V 
Naamati, Adi 
Greenwood, Edward JD  ORCID logo


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 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 cycle progression in HIV-infected cells.



Research Advance, Microbiology and Infectious Disease, HIV, Vif, PP2A, cell cycle, Virus

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eLife Sciences Publications, Ltd
Medical Research Council (MR/P008801/1)
NHS Blood and Transplant (WPA15-02)
Wellcome (210688/Z/18/Z)