ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction.
Kei MiyakawaSatoko MatsunagaKazuhiko KanouAtsushi MatsuzawaRyo MorishitaAyumi KudohKeisuke ShindoMasaru YokoyamaHironori SatoHirokazu KimuraTomohiko TamuraNaoki YamamotoHidenori IchijoAkifumi Takaori-KondoAkihide RyoPublished in: Nature communications (2015)
APOBEC3G (A3G) is an innate antiviral restriction factor that strongly inhibits the replication of human immunodeficiency virus type 1 (HIV-1). An HIV-1 accessory protein, Vif, hijacks the host ubiquitin-proteasome system to execute A3G degradation. Identification of the host pathways that obstruct the action of Vif could provide a new strategy for blocking viral replication. We demonstrate here that the host protein ASK1 (apoptosis signal-regulating kinase 1) interferes with the counteraction by Vif and revitalizes A3G-mediated viral restriction. ASK1 binds the BC-box of Vif, thereby disrupting the assembly of the Vif-ubiquitin ligase complex. Consequently, ASK1 stabilizes A3G and promotes its incorporation into viral particles, ultimately reducing viral infectivity. Furthermore, treatment with the antiretroviral drug AZT (zidovudine) induces ASK1 expression and restores the antiviral activity of A3G in HIV-1-infected cells. This study thus demonstrates a distinct function of ASK1 in restoring the host antiviral system that can be enhanced by AZT treatment.
Keyphrases
- human immunodeficiency virus
- hiv infected
- antiretroviral therapy
- hiv positive
- hiv aids
- hepatitis c virus
- hiv infected patients
- sars cov
- cell cycle arrest
- hiv testing
- binding protein
- oxidative stress
- immune response
- men who have sex with men
- signaling pathway
- induced apoptosis
- cell death
- protein protein
- transcription factor
- tyrosine kinase
- small molecule