Contribution of lipid droplets in the replicative cycle of SARS-CoV-2 in adipocytes

• Grant number: 22/02038-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2022
• Status: Discontinued
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Mariana Kiomy Osako
• Grantee: Luan dos Santos de Oliveira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 24/00550-5 - The role of lipid droplets in the disruption of STAT1 trafficking by SARS-CoV-2 accessory protein ORF6, BE.EP.DR

Abstract

SARS-CoV-2 is the pathogenic agent of COVID-19, a disease responsible for more than 5 million deaths in the world until the moment, with more than 360 million cases reported. An essential clinical aspect observed in patients with the disease is the more significant risk of complications associated with obesity cases. It has already been described that SARS-CoV-2 could infect the adipose tissue, with viral genome and proteins being detected in the white adipose tissue of patients that died of COVID-19. However, aspects of the SARS-CoV-2 pathogenesis in adipocytes and its relevance in the dynamics of the infection in the organism and the potential of the adipose tissue to be a viral reservoir and contribute to the virus persistence still need to be elucidated. Adipocytes have a significant presence of lipid droplets in the cytoplasm, which are dynamic organelles responsible mainly for lipid storage. In recent years, new functions have been attributed to these organelles, including functions related to the cellular immune response and the infectious process of some viruses. Nevertheless, there are no studies about the influence of lipid droplets on the infection of SARS-CoV-2 in adipose tissue cells. Thus, this project aims to investigate the contribution of lipid droplets during the replication and assembly of SARS-CoV-2 in adipocytes. Our work hypothesis is that the interaction of Rab proteins with the viral protein nsp7 favors replication and egress of SARS-CoV-2 in adipocytes: Rab18 and Rab8a recruit viral components to lipid droplets and Rab7 targets lipid droplets to lysosomes. In addition to mapping the interaction between nsp7 and components associated with lipid droplets during the replicative cycle, we will investigate the effect of inhibiting lipid droplets´ formation on the virus´s replication and egress. This work will bring an essential contribution to understanding the viral pathogenesis in the adipose tissue, its potential as a replication site and viral reservoir, and provide new information about the virus-cell interactions of SARS-CoV-2 in adipocytes for the management of severe cases of COVID-19.