Determination of SARS-CoV-2 proteins that modulate the expression of efferocytic genes in macrophages.

• Grant number: 23/15544-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Larissa Dias da Cunha
• Grantee: Wanderson Cawan Dourado Souza
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/25559-4 - Molecular mechanisms of LC3-associated phagocytosis and its role in macrophage function, AP.JP

Abstract

The process of efferocytosis, which involves the efficient removal, processing, and degradation of dead cells, is crucial for promoting tissue renewal and protecting against complications caused by excessive tissue damage accumulation. In general contexts, macrophages play an important role in phagocytosis and the elimination of these apoptotic cells. On the other hand, efferocytosis combines with other environmental signals to determine the functional reprogramming of macrophages towards an anti-inflammatory and tissue repair profile, meaning that failures in this process can lead to aggravated inflammation. Recently, our group demonstrated that the phagocytosis of apoptotic cells infected with viable SARS-CoV-2, when compared to the phagocytosis of sterile apoptotic cells, reduces the expression of efferocytic receptors in macrophages, potentially interfering with the ability of these phagocytes to promote efficient tissue repair. In this context, our hypothesis is that effector proteins of SARS-CoV-2 negatively modulate the expression of genes encoding these efferocytic receptors, impairing the internalization of new apoptotic cells. According to this hypothesis, we will express each protein encoded in an open reading frame (ORF) of the SARS-CoV-2 genome in macrophages, using a lentiviral expression system to confirm its effect on the expression of efferocytic receptors by qPCR. Additionally, potential candidates will be evaluated for their ability to interfere with the efferocytic activity of macrophages. Therefore, our goal is to associate the expression of viral components in macrophages with their ability to efficiently remove apoptotic cells.