Evaluation of pulmonary tissue damage in viral infection (SARS-CoV-2 and/or Influenza)

• Grant number: 21/00930-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2021
• End date: April 30, 2022
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Ricardo Tostes Gazzinelli
• Grantee: Mariela Pires Cabral Piccin
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 20/05527-0 - Bivalent intranasal vaccine using influenza virus expressing SARS-CoV-2 protein S (spike): protection mechanisms and lung injury, AP.R

Abstract

Respiratory syndromes are associated with lung endothelium damage. Recently, the SARS-CoV-2, the main cause of Coronavirus Disease 19 (Covid-19) was associated with several lung endothelium damages, including alveolar dysfunction. Also, regarding pulmonary injury, immunological response leads to a complex inflammatory response from resident cells into the respiratory tract. The balance between the capacity of crossing off pathogens and extension of the inflammatory response are crucial factors to succeed in the infection control by the host. Cellular communication is essential for the thriving of an organism as a whole. Behavioral cues for individual cells come from the cellular microenvironment as well as other cells or soluble mediators. Activation of these receptors by their ligands triggers cellular effects through activation of intracellular signal transduction pathways, which in turn relies heavily on post-translational modification of proteins. In particular protein, phosphorylation is a pivotal modification mechanism, based on fast and reversible covalent binding of a phosphoryl moiety to specific amino acid residues in proteins. Despite the main actors on immune innate and adaptive, platelets have been highlighted as an auxiliary actor on infections and inflammation. Further, we purpose to investigate: (i) tissue damage from lung and vascular by viral infection by in vitro model; (ii) platelet function as immune cells. The investigation of signaling transduction of vascular and pulmonary damage will be performed by RNA and protein expression/activation and validated on confocal microscopy. To drive the contribution of platelets on the immune and inflammatory response will be evaluated by co-culture between vascular or lung cells pre-incubated with Influenza and/or SARS-CoV-2. (AU)