The role of Vif oligomerization and RNA chaperone activity in HIV-1 replication

• Published in: Virus research 2012-11, Vol.169 (2), p.361-376
• Main Authors: Batisse, Julien, Guerrero, Santiago, Bernacchi, Serena, Sleiman, Dona, Gabus, Caroline, Darlix, Jean-Luc, Marquet, Roland, Tisné, Carine, Paillart, Jean-Christophe
• Format: Article
• Language: English
• Subjects: Chaperones; Cytidine deaminase; dimerization; Gag protein; genomics; HIV-1; HIV-1 - physiology; Human immunodeficiency virus 1; Infection; Infectivity; Life Sciences; messenger RNA; Molecular Chaperones - metabolism; Oligomerization; Packaging; pathogenicity; proteasomes; Protein Multimerization; Protein oligomerization; Protein structure; Replication; Replication initiation; Reverse transcription; RNA chaperone; RNA, Transfer, Lys - metabolism; RNA, Viral - metabolism; Translation; translation (genetics); Ubiquitin-protein ligase; Vif; vif Gene Products, Human Immunodeficiency Virus - metabolism; virion; Virions; Virus Assembly
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2012.06.018

► We review the importance of the HIV-1 Vif protein in the viral life cycle. ► Vif counteracts the innate antiviral factor APOBEC3G by several mechanisms. ► The multimerization of Vif is required for its function. ► RNA chaperone activity and intrinsic disordered nature of some Vif domains regulates several steps during viral assembly. The viral infectivity factor (Vif) is essential for the productive infection and dissemination of HIV-1 in non-permissive cells that involve most natural HIV-1 target cells. Vif counteracts the packaging of two cellular cytidine deaminases named APOBEC3G (A3G) and A3F by diverse mechanisms including the recruitment of an E3 ubiquitin ligase complex and the proteasomal degradation of A3G/A3F, the inhibition of A3G mRNA translation or by a direct competition mechanism. In addition, Vif appears to be an active partner of the late steps of viral replication by participating in virus assembly and Gag processing, thus regulating the final stage of virion formation notably genomic RNA dimerization and by inhibiting the initiation of reverse transcription. Vif is a small pleiotropic protein with multiple domains, and recent studies highlighted the importance of Vif conformation and flexibility in counteracting A3G and in binding RNA. In this review, we will focus on the oligomerization and RNA chaperone properties of Vif and show that the intrinsic disordered nature of some Vif domains could play an important role in virus assembly and replication. Experimental evidence demonstrating the RNA chaperone activity of Vif will be presented.