le 30 mars 2015 à 14 h
Pascal Preira, Institut de Pharmacologie et de Biologie Structurale, Toulouse

The process of HIV infection requires the sequential interaction of multiple receptors at the plasma membrane. Firstly, the gp120 viral envelope protein interacts with a CD4 receptor present at the surface of the target cell. Secondly, the same gp120 viral protein interacts with co-receptors that can be either CCR5 or CXCR4 (for R5- and X4-virus, respectively).

By Förster resonance energy transfer experiments, we previously demonstrated the constitutive association of CD4 and CCR5 at the surface of living cells. We therefore speculated that this interaction may correlate with compartimentalisation of CD4 and CCR5 within the plasma membrane.

By means of Fluorescence Recovery after Photobleaching at variable radii (FRAPrv) and Single Particle Tracking (SPT), we characterised the lateral distribution and the dynamics of these receptors at the surface of living cells. We first observed, by FRAPrv on HEK cells stably expressing CD4 and/or CCR5, that CD4-CCR5 interaction involves multiple CCR5 molecules per CD4 and induces a confinement into μm-sized non-raft domains of both receptors. Recently, SPT experiments carried out on T-lymphocytes allowed us to have a more precise view of receptors behaviour and confinement within the plasma membrane of living T-lymphocytes. It also revealed that the use of Maraviroc®, an antiretroviral drug belonging to the CCR5 receptor antagonist class, disrupts CD4-CCR5 interactions and modifies the CD4 dynamic behaviour within the membrane.

These results suggest that the clustering of CD4 and CCR5 into domains might facilitate HIV entry and might play a role in the predominance of R5 viruses in the early phase of the infection at the expense of the X4 viruses.

Lieu(x) :         Amphithéatre Curie, Ecole Polytechnique

Contact :       Antigoni Alexandrou
                      antigoni.alexandrou at polytechnique.edu

À télécharger :       Séminaire PREIRA.pdf - PDF