ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25901786.
- Also identified by DOI 10.1038/ncomms7945 and PMC identifier 4423214.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Cytidine Deaminase
- HIV-1
- MAP Kinase Kinase Kinase 5
- Ubiquitin-Protein Ligase Complexes
- Virion
- vif Gene Products, Human Immunodeficiency Virus