PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation.
Nat Commun
; 10(1): 1844, 2019 04 23.
Article
em En
| MEDLINE
| ID: mdl-31015445
ABSTRACT
Lentiviruses have evolved to acquire an auxiliary protein Vpx to counteract the intrinsic host restriction factor SAMHD1. Although Vpx is phosphorylated, it remains unclear whether such phosphorylation indeed regulates its activity toward SAMHD1. Here we identify the PIM family of serine/threonine protein kinases as the factors responsible for the phosphorylation of Vpx and the promotion of Vpx-mediated SAMHD1 counteraction. Integrated proteomics and subsequent functional analysis reveal that PIM family kinases, PIM1 and PIM3, phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1. Inhibition of the PIM kinases promotes the antiviral activity of SAMHD1, ultimately reducing viral replication. Our results highlight a new mode of virus-host cell interaction in which host PIM kinases facilitate promotion of viral infectivity by counteracting the host antiviral system, and suggest a novel therapeutic strategy involving restoration of SAMHD1-mediated antiviral response.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Proteínas Proto-Oncogênicas
/
HIV-2
/
Proteínas Serina-Treonina Quinases
/
Proteínas Proto-Oncogênicas c-pim-1
/
Proteínas Virais Reguladoras e Acessórias
/
Interações Hospedeiro-Patógeno
/
Proteína 1 com Domínio SAM e Domínio HD
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Japão