Nuclear import of the HIV-1 REV Protein
Human immunodeficiency virus type 1 (HIV-1) attacks human cells by hijacking their biological mechanisms to replicate and spread. A key element in this process is the HIV-1 Rev protein, which plays a central role in regulating viral replication. The HIV-1 Rev protein plays a central role in viral replication within infected human cells. Rev acts as a shuttle that transports viral RNAs out of the nucleus, an essential step in the production of new viral particles. To enter the nucleus, Rev collaborates with host cell proteins, two of which are essential : Importin β and Nucleophosmin 1 (NPM1). Despite the importance of these cellular players in the viral infection cycle, the precise mechanisms leading to the association of Rev with these proteins remain poorly understood. Characterising this essential step, which is not targeted by existing antiviral treatments, could ultimately lead to the development of new therapeutic tools.
This project aims to decipher the mechanisms by which Rev binds and cooperates with its partners to enter the nucleus and ensure viral replication, by obtaining molecular and dynamic details of these interactions. This project is based on an integrative biology approach, involving several teams with complementary expertise.
Collaborations
. Malene Jensen (SIGNAL group, IBS)
. Guy Schoehn (MEM group, IBS)
. Nathalie Arhel (VTRIS team, IRIM, Montpellier)
Publications
Spittler D, Indorato RL, Boeri Erba E, Delaforge E, Signor L, Harris SJ, Garcia-Saez I, Palencia A, Gabel F, Blackledge M, Noirclerc-Savoye M, Petosa C. Binding stoichiometry and structural model of the HIV-1 Rev/importin β complex. Life Sci Alliance. 2022 Aug 22 ;5(10):e202201431. DOI : 10.26508/lsa.202201431
Ben Fadhel, N., Signor, L., Petosa, C. & Noirclerc-Savoye, M. Phosphomimetic mutations modulate the ability of HIV-1 Rev to bind human Importin β in vitro. Matters (2019). DOI : : hal-02270755