Inflammasome genetics as a risk factor for the clinical heterogeneity of SARS-Cov-2 infection

• Grant number: 21/05420-4
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: February 29, 2024
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Alessandra Pontillo
• Grantee: Alessandra Pontillo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Vinícius Nunes Cordeiro Leal

Abstract

Since the beginning of the COVID-19 pandemic, it has become clear that only a low percentage of individuals infected by the SARS-CoV-2 virus had a severe clinical picture with lung damage and/or extrapulmonary disease, which could lead to death. It clear suggests an individual predisposition partly constituted by the host genetic background.Taking into account that the activation of the inflammasome may occur in the SARS-CoV-2 infection as it happens with other coronaviruses, that an exacerbated production of IL-1ß and/or IL-18 may contribute for the exacerbate inflammatory response observed in severe cases of the disease, and that inflammasome genetic polymorphisms have already been associated with viral infections, and with clinical presentations similar to those of severe COVID-19 (i.e.: shock and sepsis, lung diseases, kidney disease, coagulopathies) the hypothesis of this project is that a genetic-based greater (disregulated) activation of the inflammasome may be directly related to the development of severe forms of SARS-CoV-2 disease.Therefore, we intend to evaluate the level of activation of the complex through two approaches: study of genetic association and cell specific genotype-guided assays. Therefore, single-base polymorphisms (SNPs) in the inflammasome genes will be genotyped in patients infected with SARS-CoV.2, and the distribution of SNPs will be analyzed according to the patients' clinical presentation. At the same time, through genotype-guided assays we want to characterize the cell-specific effect of the associated variants.In this way, we hope to identify risk factors for a more severe form of COVID-19, and to characterize the inflammasome activation pathways involved in the disease. The preliminary data presented justify our hypothesis and the development of the study. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LEAL, VINICIUS NUNES CORDEIRO; ROA, MARIELA ESTEFANY GISLANE VERA; CANTONI, JULIA SILVA; DOS REIS, EDIONE CRISTINA; LARA, AMANDA NAZARETH; PONTILLO, ALESSANDRA. Integrated Genetic and Cellular Analysis Reveals NLRP1 Activation in CD4+T Lymphocytes During Chronic HIV Infection. IMMUNOLOGICAL INVESTIGATIONS, v. N/A, p. 20-pg., 2024-11-01. (21/05420-4, 20/15323-3, 19/06363-4, 17/10824-1, 24/09016-1)

MENDONCA, LEONARDO OLIVEIRA; LEAL, VINICIUS N. C.; ROA, MARIELA E. G., V; BARROS, SAMAR FRESCHI; KALIL, JORGE; PONTILLO, ALESSANDRA. Unexplained fever with consumptive syndrome in the elderly: two cases of VEXAS syndrome with inflammasome dysregulation. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, v. 218, n. 2, p. 8-pg., 2024-09-08. (20/15323-3, 21/05420-4)