Abstract
Human immunodeficiency virus-1 (HIV-1) Vif is essential for viral evasion of host antiviral factor CEM15/APOBEC3G. We report that Vif interacts with cellular proteins Cul5, elongins B and C, and Rbx1 to form an Skp1-cullin-F-box (SCF)-like complex. The ability of Vif to suppress antiviral activity of APOBEC3G was specifically dependent on Cul5-SCF function, allowing Vif to interact with APOBEC3G and induce its ubiquitination and degradation. A Vif mutant that interacted with APOBEC3G but not with Cul5-SCF was functionally inactive. The Cul5-SCF was also required for Vif function in distantly related simian immunodeficiency virus mac. These results indicate that the conserved Cul5-SCF pathway used by Vif is a potential target for antiviral development.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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APOBEC-3G Deaminase
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Line
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Cullin Proteins / genetics
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Cullin Proteins / metabolism*
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Cytidine Deaminase
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Elongin
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Gene Products, vif / genetics
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Gene Products, vif / metabolism*
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HIV-1 / genetics
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HIV-1 / physiology*
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Humans
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Mutation
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Nucleoside Deaminases
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Proteins / metabolism*
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Repressor Proteins
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transfection
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Ubiquitin / metabolism*
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Virus Replication
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vif Gene Products, Human Immunodeficiency Virus
Substances
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Carrier Proteins
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Cullin Proteins
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Elongin
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Gene Products, vif
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Proteins
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RBX1 protein, human
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Repressor Proteins
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Transcription Factors
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Ubiquitin
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vif Gene Products, Human Immunodeficiency Virus
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Nucleoside Deaminases
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APOBEC-3G Deaminase
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APOBEC3G protein, human
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Cytidine Deaminase