SARS-CoV-2 interactions with adipose tissue and implications for viral pathogenesis

• Grant number: 21/00218-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2023
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Mariana Kiomy Osako
• Grantee: Ana Beatriz do Anjos Souza
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 23/08666-0 - Lipid droplets as viral carriers in adipocytes, BE.EP.DR

Abstract

During the outbreak of COVID-19 by the SARS-CoV-2 virus, a high prevalence of severe acute respiratory syndrome was observed in overweight and obese patients, who also had a higher rate of hospitalization and admission to intensive care units. Obese patients show a greater risk of developing more severe forms of COVID-19; therefore, this project aims to elucidate the interactions between the adipose tissue and SARS-CoV-2 and its implications for viral pathogenesis. For this, we will evaluate the susceptibility and permissiveness of adipocytes to SARS-CoV2 infection and investigate the mechanisms of its replication and persistence and the contribution of the infected adipocyte in the production of pro-inflammatory cytokine. We will also assess whether the chronic, low-grade inflammation found in the adipose tissue of obese patients contributes to increased infectivity and viral replication in adipocytes. In preliminary experiments, we identified that 3T3-L1 adipocytes are permissive to SARS-CoV-2 virus infection and that lipid droplets may play a role in their replication. Thus, we will investigate the lipid droplet metabolism in SARS-CoV-2 replication and lipogaphy functionality in infected adipose tissue and its ability to alter fatty acid storage and induce differentiation into beige tissue. The persistence of SARS-CoV-2 will also be evaluated in infected adipocytes for 30 days. The presence of the virus will be investigated in samples of white adipose tissue from autopsies of patients with COVID-19. Studies aimed at deepening the knowledge of the interactions of SARS-CoV-2 with adipose tissue cells are of great relevance to understanding viral pathogenesis to provide adequate clinical management of the disease in obese patients and evaluate possible long-term impacts on patients who have had COVID-19.