Analyse d’une imagerie in vivo de l’infection de cellules par le VIH

Characterisation of the infection of mucosal cells with HIV, recorded in real-time using a microscope and analysed using the Imaris software package. To view the different elements involved in infection, the cells producing the virus have been modified to produce a fluorescent virus that contains green fluorescent proteins (GFP), while the genital mucosal cells have been genetically modified so that they express a red fluorescent protein (RFP) on the surface. The research scientists then reproduce, in vivo, the first stage of the mucosal entry of the virus, i.e. the transfer of HIV from an infected cell to a male genital cell. Watching this in real time using the microscope take one hour, during which time the cells (infected and target) are scanned continuously. By superimposing around 100 sections of these scans, the scientists obtain a reconstruction in space and time (4D). This has made it possible to demonstrate that infected cells, when they come into contact with the epithelial cells, form a tight connection with the target mucosal cells. This is referred to as a viral synapse, which stimulates local production of the virus. The virus can then cross the epithelial barrier via transcytosis, a transcellular transportation mechanism. This viral synapse causes the mucosal cell to secrete cytokines, including thymic stromal lymphopoietin (TSLP), which in this case acts as a chemokine. Chemokines are proteins that control the positioning of immune cells in tissues. The TSLP secreted by these mucosal cells attracts Langerhans cells towards the lumen of the mucosa. These Langerhans cells then capture the virus and start the infection proper. The "Mucosal entry of HIV and mucosal immunity" team led by Morgane Bomsel is attempting to target TSLP in order to develop a prophylactic treatment that prevents the mucosal transmission of the virus, which is the main entry route of HIV into the organism.