A tripartite complex HIV-1 Tat-cyclophilin A-capsid protein enables Tat encapsidation that is required for HIV-1 infectivity

• Published in: bioRxiv
• Main Authors: Schatz, Malvina, Marty, Laetitia, Ounadjela, Camille, Phuoc Bao Viet Tong, Cardace, Ilaria, Mettling, Clément, Pierre-Emmanuel Milhiet, Costa, Luca, Godefroy, Cédric, Pugnière, Martine, Jean-François Guichou, Jean-Michel Mesnard, Blaise, Mickael, Beaumelle, Bruno
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 08.08.2022
• Subjects: Capsid protein; Encapsidation; Gene expression; HIV; Human immunodeficiency virus; Infectivity; Proteins; Tat protein; Virions
• DOI: 10.1101/2022.08.07.503104

HIV-1 Tat is a key viral protein that stimulates several steps of viral gene expression. Tat is especially required for the transcription of viral genes but it is still not clear if and how Tat is incorporated into HIV-1 virions. Cyclophilin A (CypA) is a prolylisomerase that binds to HIV-1 capsid protein (CA) and is thereby encapsidated. Here we found that a Tat-CypA-CA tripartite complex assembles in HIV-1 infected cells. Biochemical and biophysical studies showed that high affinity interactions drive the assembly of this complex. Virions devoid of encapsidated Tat showed a 5-10 fold decrease in HIV-infectivity and, conversely, encapsidating Tat into ΔTat viruses greatly enhanced infectivity. The absence of encapsidated Tat decreases the efficiency of retrotranscription by ~50% and transcription by 99%. We thus identified a Tat-CypA-CA complex that enables Tat encapsidation and showed that encapsidated Tat is required to initiate robust HIV-1 infection and viral production. Competing Interest Statement The authors have declared no competing interest.