Abstract
The HIV-1 accessory protein Vif (virion infectivity factor) is required for the production of infectious virions by CD4(+) lymphocytes. Vif facilitates particle infectivity by blocking the inhibitory activity of APOBEC3G (CEM15), a virion-encapsidated cellular protein that deaminates minus-strand reverse transcript cytosines to uracils. We report that HIV-1 Vif forms a complex with human APOBEC3G that prevents its virion encapsidation. HIV-1 Vif did not efficiently form a complex with mouse APOBEC3G. Vif dramatically reduced the amount of human APOBEC3G encapsidated in HIV-1 virions but did not prevent encapsidation of mouse or AGM APOBEC3G. As a result, these enzymes are potent inhibitors of wild-type HIV-1 replication. The species-specificity of this interaction may play a role in restricting HIV-1 infection to humans. Together these findings suggest that therapeutic intervention that either induced APOBEC3G or blocked its interaction with Vif could be clinically beneficial.
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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Antiviral Agents / pharmacology
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Capsid / metabolism
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Capsid / virology
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Cell Line
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Cytidine Deaminase
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DNA, Complementary / genetics
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Gene Expression Regulation, Viral / genetics
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Gene Products, vif / metabolism*
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HIV Infections / drug therapy
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HIV Infections / enzymology*
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HIV Infections / virology*
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HIV-1 / enzymology*
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HIV-1 / pathogenicity
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Humans
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Macromolecular Substances
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Mice
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Molecular Sequence Data
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Mutation / genetics
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Nucleoside Deaminases
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Protein Binding / genetics
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Proteins / metabolism*
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Repressor Proteins
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Species Specificity
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Transcription, Genetic / genetics
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Virion / enzymology*
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Virus Replication / physiology*
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vif Gene Products, Human Immunodeficiency Virus
Substances
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Antiviral Agents
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DNA, Complementary
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Gene Products, vif
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Macromolecular Substances
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Proteins
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Repressor Proteins
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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
Associated data
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GENBANK/AY331714
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GENBANK/AY331715
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GENBANK/AY331716