Project

The COVID-19 pandemic has prompted researchers to focus on the mechanisms by which the virus triggers host pathogenicity. My project focuses on the envelope protein E of SARS-CoV-2, a structural protein containing at its C-terminal end a PDZ Binding Motif (PBM) able to interact with host PDZ proteins located at cell junctions and involved in polarity (ZO1, MPP5, LNX2, PARD3, MLLT4). Targeting cellular junctions and polarity components is a common strategy used by viruses to hijack the cell machinery to their advantage, and the E protein PBM plays a key role in epithelial barrier disruption during infection. By producing viruses lacking this PBM (in collaboration with the PFR1 Covid Task Force), we have shown its key role in pathogenicity in the hamster model. In parallel, I also monitored epithelial perturbations in cell lines and in a lung-on-chip model. To complete these results, it is crucial to consider an RNA sequencing in order to observe differences in the global gene expression between SARS-CoV-2 WT and mutant lacking the PBM. This mights be also relevant to focus on 2 organs, the brain and the lung, considering these tropisms of the disease.