A Tripartite Complex HIV-1 Tat-Cyclophilin A-Capsid Protein Enables Tat Encapsidation That Is Required for HIV-1 Infectivity
Malvina Schatz, Laëtitia Marty, Camille Ounadjela, Phuoc Bao Viet Tong, Ilaria Cardace, Clément Mettling, Pierre‐Emmanuel Milhiet, Luca Costa, Cédric Godefroy, Martine Pugnière, Jean‐François Guichou, Jean-Michel Mesnard, Mickaël Blaise, Bruno Beaumelle
Abstract
The viral transactivating protein Tat has been shown to stimulate several steps of HIV gene expression. It was found to facilitate reverse transcription. Moreover, Tat is strictly required for the transcription of viral genes. Although the presence of Tat within HIV virions would undoubtedly favor these steps and therefore enable the incoming virus to boost initial viral production, whether and how Tat is present within virions has been a matter a debate. We here described and characterized a tripartite complex between Tat, HIV capsid protein, and the cellular chaperone cyclophilin A that enables efficient and specific Tat encapsidation within HIV virions. We further showed that Tat encapsidation is required for the virus to efficiently initiate infection and viral production. This effect is mainly due to the transcriptional activity of Tat.