Impact of SARS-CoV-2 Protein Expression on Lipid Droplet Dynamics in Human Hepatocytes

• Grant number: 25/04287-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Mariana Kiomy Osako
• Grantee: Julia dos Santos Lacerda
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The SARS-CoV-2 virus, responsible for COVID-19, has caused over 7 million deaths worldwide, with more than 700 million reported cases. A clinical aspect observed in patients with the disease is the increased risk of complications associated with obesity. In addition to increased adipose tissue, obesity also results in greater lipid accumulation in the liver, leading to hepatic steatosis. It has been demonstrated that SARS-CoV-2 infects liver tissue, positively detecting the viral genome and proteins. Hepatic steatosis arises from an increase in the number and volume of lipid droplets (LDs), which are dynamic organelles responsible for lipid storage. Recently, new functions have been attributed to these organelles, including their role in viral infections. Recent studies have shown that LDs accumulate in hepatocytes of COVID-19 patients and that the structural Spike protein induces the formation of lipid droplets. However, the subcellular localization of structural proteins, such as N protein, remains an active area of research, as the accessory proteins ORF3a and ORF9b play roles in the virulence of SARSCoV-2, blocking the autophagy process and reducing mitochondrial protein levels, respectively. Therefore, this study aims to evaluate whether the structural proteins S and N colocalize with LDs. We will also analyze the non-structural proteins ORF3a and ORF9b and their influence on the number and volume of LDs in hepatocytes infected with SARS-CoV-2. With this study, we expect to contribute to the understanding of viral pathogenesis and how liver tissue infection may contribute to more severe cases of COVID-19.