Production of infectious virus and degradation of APOBEC3G are separable functional properties of human immunodeficiency virus type 1 Vif

• Published in: Virology (New York, N.Y.) Vol. 369; no. 2; pp. 329 - 339
• Main Authors: Kao, Sandra, Goila-Gaur, Ritu, Miyagi, Eri, Khan, Mohammad A, Opi, Sandrine, Takeuchi, Hiroaki, Strebel, Klaus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.12.2007
• Subjects: APOBEC-3G Deaminase; APOBEC3G; Cell Line; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; Genes, vif; HeLa Cells; HIV-1 - genetics; HIV-1 - pathogenicity; HIV-1 - physiology; Human immunodeficiency virus 1; Human Immunodeficiency Virus Proteins - genetics; Human Immunodeficiency Virus Proteins - physiology; Humans; Infectious Disease; Protein degradation; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Transfection; Vif; vif Gene Products, Human Immunodeficiency Virus - genetics; vif Gene Products, Human Immunodeficiency Virus - physiology; Virus Replication; Virus–host interactions; Virus–host interactions; Vif; Protein degradation; APOBEC3G
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2007.08.005

Abstract HIV-1 Vif regulates viral infectivity by inhibiting the encapsidation of APOBEC3G (APO3G) through proteasomal degradation of the protein. Here we compared various Vif proteins for their ability to induce APO3G degradation and rescue viral infectivity. We found that Vif expressed from proviral vectors caused relatively inefficient degradation of APO3G in HeLa cells yet was very effective in inhibiting APO3G's antiviral activity. On the other hand, Vif expressed autonomously from a codon-optimized vector caused very efficient APO3G degradation and also effectively inhibited APO3G's antiviral effects. In contrast, a Vif chimera containing an N-terminal fluorescent tag efficiently induced APO3G degradation but was unable to restore viral infectivity. The lack of a direct correlation between APO3G degradation and rescue of viral infectivity suggests that these two properties of Vif are functionally separable. Our data imply that intracellular degradation of APO3G may not be the sole activity of Vif required for the production of infectious virions from APO3G-expressing cells.