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ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction
- Source :
- Nature Communications
- Publication Year :
- 2014
-
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.<br />The human protein APOBEC3G (A3G) inhibits HIV-1 replication, but the viral protein Vif counteracts by inducing A3G degradation. Here Miyakawa et al. show that the antiretroviral drug AZT restores A3G function in vitro by stimulating expression of a host protein, ASK1, which interferes with the action of Vif.
- Subjects :
- Anti-HIV Agents
viruses
Immunology
General Physics and Astronomy
APOBEC-3G Deaminase
Biology
MAP Kinase Kinase Kinase 5
Virus Replication
Microbiology
General Biochemistry, Genetics and Molecular Biology
Article
Zidovudine
Virology
Cytidine Deaminase
medicine
vif Gene Products, Human Immunodeficiency Virus
Humans
Immunoprecipitation
ASK1
APOBEC3G
Infectivity
chemistry.chemical_classification
DNA ligase
Multidisciplinary
Kinase
Ubiquitination
Virion
virus diseases
Ubiquitin-Protein Ligase Complexes
General Chemistry
biochemical phenomena, metabolism, and nutrition
Biological sciences
HEK293 Cells
chemistry
Viral replication
Apoptosis
HIV-1
medicine.drug
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....3cc47a15db222e5dd074392ceaaa5863