Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest.
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Marelli, S., Williamson, J., Protasio, A. V., Naamati, A., Greenwood, E., Deane, J., Lehner, P., & et al. (2020). Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest.. eLife, 9 https://doi.org/10.7554/elife.53036
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.
Humans, HIV-1, Flow Cytometry, Point Mutation, vif Gene Products, Human Immunodeficiency Virus, Protein Phosphatase 2, Cell Cycle Checkpoints, APOBEC Deaminases, Host Microbial Interactions
Wellcome Trust (210688/Z/18/Z)
External DOI: https://doi.org/10.7554/elife.53036
This record's URL: https://www.repository.cam.ac.uk/handle/1810/319862
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/