Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest.
Elife
; 92020 04 15.
Article
in En
| MEDLINE
| ID: mdl-32292164
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
HIV-1
/
Protein Phosphatase 2
/
Vif Gene Products, Human Immunodeficiency Virus
/
Cell Cycle Checkpoints
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Elife
Year:
2020
Document type:
Article
Affiliation country:
Reino Unido