Species-Specific Exclusion of APOBEC3G from HIV-1 Virions by Vif

• Published in: Cell Vol. 114; no. 1; pp. 21 - 31
• Main Authors: Mariani, Roberto, Chen, Darlene, Schröfelbauer, Bärbel, Navarro, Francisco, König, Renate, Bollman, Brooke, Münk, Carsten, Nymark-McMahon, Henrietta, Landau, Nathaniel R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.07.2003
• Subjects: Animals; Antiviral Agents - pharmacology; APOBEC-3G Deaminase; Capsid - metabolism; Capsid - virology; Cell Line; Cytidine Deaminase; DNA, Complementary - genetics; Gene Expression Regulation, Viral - genetics; Gene Products, vif - metabolism; HIV Infections - drug therapy; HIV Infections - enzymology; HIV Infections - virology; HIV-1 - enzymology; HIV-1 - pathogenicity; Humans; Macromolecular Substances; Mice; Molecular Sequence Data; Mutation - genetics; Nucleoside Deaminases; Protein Binding - genetics; Proteins - metabolism; Repressor Proteins; Species Specificity; Transcription, Genetic - genetics; vif Gene Products, Human Immunodeficiency Virus; Virion - enzymology; Virus Replication - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(03)00515-4

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.