Topics: Transcriptomics (Illumina)
Origin: IP
Project type: Expertise
Name of Applicant: Flavio ALVAREZ
Date of application: 29-11-2023
Unit: Channel Receptors
Location: Metchnikof 1st floor
Phone: +33664168091
@ Mail: flavio.alvarez@pasteur.fr
@ PI-Mail: pierre-jean.corringer@pasteur.fr
Project context and summary: 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.
Related team publications:de Melo GD, Perraud V, Alvarez F, Vieites-Prado A, Kim S, Kergoat L, Coleon A, Trüeb BS, Tichit M, Piazza A, Thierry A, Hardy D, Wolff N, Munier S, Koszul R, Simon-Lorière E, Thiel V, Lecuit M, Lledo PM, Renier N, Larrous F, Bourhy H. Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants. Nat Commun. 2023 Jul 26;14(1):4485. doi: 10.1038/s41467-023-40228-7. PMID: 37495586; PMCID: PMC10372078.
Zhu Y, Alvarez F, Wolff N, Mechaly A, Brûlé S, Neitthoffer B, Etienne-Manneville S, Haouz A, Boëda B, Caillet-Saguy C. Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins. Front Microbiol. 2022 Feb 23;13:829094. doi: 10.3389/fmicb.2022.829094. PMID: 35283834; PMCID: PMC8909127.
de Melo GD, Lazarini F, Levallois S, Hautefort C, Michel V, Larrous F, Verillaud B, Aparicio C, Wagner S, Gheusi G, Kergoat L, Kornobis E, Donati F, Cokelaer T, Hervochon R, Madec Y, Roze E, Salmon D, Bourhy H, Lecuit M, Lledo PM. COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters. Sci Transl Med. 2021 Jun 2;13(596):eabf8396. doi: 10.1126/scitranslmed.abf8396. Epub 2021 May 3. PMID: 33941622; PMCID: PMC8158965.
Manager: iakov.vitrenko@pasteur.frStatus: Closed