Tail-Interacting Protein TIP47 Is a Connector between Gag and Env and Is Required for Env Incorporation into HIV-1 Virions

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 40; pp. 14947 - 14952
• Main Authors: Lopez-Vergès, Sandra, Camus, Grégory, Blot, Guillaume, Beauvoir, Roxane, Benarous, Richard, Berlioz-Torrent, Clarisse
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 03.10.2006; National Acad Sciences
• Subjects: Amino Acid Sequence; Amino Acids; Binding sites; Biological Sciences; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - metabolism; Gene Expression; Gene Products, env - metabolism; Gene Products, gag - metabolism; Genetic mutation; HeLa Cells; HIV; HIV 1; HIV Envelope Protein gp41 - metabolism; HIV-1 - metabolism; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Incorporation; Infections; Intracellular Signaling Peptides and Proteins - deficiency; Intracellular Signaling Peptides and Proteins - metabolism; Jurkat Cells; Molecular Sequence Data; Mutation; Mutation - genetics; Packaging; Perilipin-3; Pregnancy Proteins - deficiency; Pregnancy Proteins - metabolism; Protein Binding; Protein Structure, Tertiary; Proteins; Small interfering RNA; T lymphocytes; Vesicular Transport Proteins; Viral Matrix Proteins - chemistry; Virion - metabolism; Virions; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0602941103

The presence of the envelope glycoprotein Env in HIV-1 virions is essential for infectivity. To date, the molecular mechanism by which Env is packaged into virions has been largely unknown. Here, we show that TIP47 (tail-interacting protein of 47 kDa), which has been shown to interact with Env, also binds the MA (matrix) domain of HIV-1 Gag protein and that these three proteins form a ternary complex. Mutations in Gag that abrogate interaction with TIP47 inhibit Env incorporation and virion infectivity as well as colocalization between Gag and Env. We also show that TIP47 silencing impairs Env incorporation and infectivity and abolishes coimmunoprecipitation of Gag with Env. In contrast, overexpression of TIP47 increases Env packaging. Last, we demonstrate that TIP47 can interact simultaneously with Env and Gag. Taken together, our results show that TIP47 is a cellular cofactor that plays an essential role in Env incorporation, allowing the encounter and the physical association between HIV-1 Gag and Env proteins during the viral assembly process.