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Conserved and non-conserved features of HIV-1 and SIVagm Vif mediated suppression of APOBEC3 cytidine deaminases
- Source :
- Cellular microbiology. 10(8)
- Publication Year :
- 2008
-
Abstract
- Human cytidine deaminase APOBEC3C (A3C) acts as a potent inhibitor of SIVagm and can be regulated by both HIV-1 and SIVagm Vif. The mechanism by which Vif suppresses A3C is unknown. In the present study, we demonstrate that both HIV-1 and SIVagm Vif can act in a proteasome-dependent manner to overcome A3C. SIVagm Vif requires the Cullin5-ElonginB-ElonginC E3 ubiquitin ligase for the degradation of A3C as well as the suppression of its antiviral activity. Mutation of a residue critical for the species-specific recognition of human or monkey A3G by HIV-1 Vif or SIVagm Vif in A3C had little effect on HIV-1 or SIVagm Vif-mediated degradation of A3C. Although the amino-terminal region of A3G was not important for Vif-mediated degradation, the corresponding region in A3C was critical. A3C mutants that were competent for Vif binding but resistant to Vif-mediated degradation were identified. These data suggest that primate lentiviral Vif molecules have evolved to recognize multiple host APOBEC3 proteins through distinct mechanisms. However, Cul5-E3 ubiquitin ligase appears to be a common pathway hijacked by HIV-1 and SIV Vif to defeat APOBEC3 proteins. Furthermore, Vif and APOBEC3 binding is not sufficient for target protein degradation indicating an important but uncharacterized Vif function.
- Subjects :
- Models, Molecular
Proteasome Endopeptidase Complex
Gene Products, vif
animal diseases
viruses
Immunology
Mutant
medicine.disease_cause
Microbiology
Article
Cell Line
Cytosine Deaminase
chemistry.chemical_compound
Species Specificity
Virology
Cytidine Deaminase
medicine
vif Gene Products, Human Immunodeficiency Virus
Animals
Humans
APOBEC Deaminases
Genetics
Mutation
biology
virus diseases
Cytidine
Cytidine deaminase
Haplorhini
Simian immunodeficiency virus
biochemical phenomena, metabolism, and nutrition
Cullin Proteins
Ubiquitin ligase
chemistry
biology.protein
HIV-1
Simian Immunodeficiency Virus
Target protein
Function (biology)
Subjects
Details
- ISSN :
- 14625822
- Volume :
- 10
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cellular microbiology
- Accession number :
- edsair.doi.dedup.....f35ba61c77cb184be9121a3aadc6a58d