Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest.
Elife
; 92020 04 15.
Article
en 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
VIH-1
/
Proteína Fosfatasa 2
/
Productos del Gen vif del Virus de la Inmunodeficiencia Humana
/
Puntos de Control del Ciclo Celular
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Elife
Año:
2020
Tipo del documento:
Article
País de afiliación:
Reino Unido