Team website : http://retrovirus.ibcp.fr
Retroviruses are characterized by their ability to gain resistance from therapeutic or vaccinal intervention through the accumulation of escape mutations in the viral genome and/or the interaction of regulatory viral proteins with cellular pathways. Understanding the structural determinants of the functions of the viral proteins is crucial for the development of efficient antiviral therapies.
Our research are conducted on both animal and human retroviruses to take advantage of the presence in the Biodistrict Lyon-Gerland of the CIRI (International Center for Infectiology Research) and of the world-leading companies Merial and Sanofi, which are dedicated to animal and human health, respectively.
Hence, we have characterized the crystal structure of an epitope of the trans-activator Tat of the human virus HIV-1 in complex with its cognate antibody (Serrière et al., J. Mol. Biol. 2011), observed a new dimeric form of an avian integrase domain (Ballandras et al., PloS One 2011), characterized the biophysical properties of the capsid protein of the Feline Immunodeficiency Virus FIV (Serrière et al., PloS One 2013) and determined the crystal structure of the matrix protein of FIV (Serrière et al., Retrovirology 2013).
We also have a genuine interest for some non-viral therapeutic targets and we have carried out structural studies on taurocyamine kinases in trematodes (Merceron et al., J. Biol. Chem. 2015) and the bacterial type 2 secretion system (Pineau et al., Mol. Microbiol. 2014).
On-going projects on retroviral integrases aim to rationally develop new classes of protein-protein inhibitors to fight AIDS (P. Gouet, H. Yajjou in coll. with C. Ronfort and L. Guy) and to make safer the use of pig tissues and organs in human xenotransplantation (P. Gouet, M. Chahpazoff in coll. with Y. Blanchard). Molecular and structural studies of chromosomal targeting by integrases are underway (P. Gouet, X. Robert in coll. with V. Parissi) and we have started observing the concerted integration mechanism at the single molecule scale with magnetic tweezers (S. Réty, F. Fiorini in coll. with P. Jalinot).
We also work on the molecular mechanisms underlying the biological function of the transactivating protein Tax from Human T-Lymphotropic Virus (HTLV), whose structure is unknown (C. Guillon, C. Folio, M. Dujardin in coll. with R. Mahieux and G. Schoehn). Tax is a modular protein with disordered regions and we use a structural biological integrative approach combining X-ray crystallography, NMR and cryo-EM.
Furthermore, we aim at the identification of therapeutic molecules targeting assembly of the capsid protein of FIV by a combination of in vitro screening, bio-guided design process and structural studies (C. Guillon in coll. with G. Álvarez Touron).
By clicking on the PDB logo, you will be redirected to the Protein Data Bank website presenting the extensive list of the structures we solved @IBCP.