The role of lipid droplets in the disruption of STAT1 trafficking by SARS-CoV-2 accessory protein ORF6

• Grant number: 24/00550-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Mariana Kiomy Osako
• Grantee: Luan dos Santos de Oliveira
• Supervisor: Toru Okamoto
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Juntendo University, Japan
• Associated to the scholarship: 22/02038-4 - Contribution of lipid droplets in the replicative cycle of SARS-CoV-2 in adipocytes, BP.DR

Abstract

Lipid droplets are dynamic organelles mainly responsible for storing neutral lipids and as a source of lipids for membrane synthesis. Despite their importance for cellular homeostasis, new functions have been attributed to these organelles recently, such as participation in the innate immune response and the infectious process of certain pathogens. Concerning viruses, lipid droplets play an important role during infection by Dengue, Zika and Hepatitis C viruses, among others. Recent studies also demonstrated a role for lipid droplets during SARS-CoV-2 infection. SARS-CoV-2 is the pathogenic agent that causes COVID-19, a disease that has been responsible for more than 6 million deaths worldwide, with around 700 million reported cases. Furthermore, the presence of SARS-CoV-2 viral proteins in lipid droplets raises questions regarding the disruption of lipid droplet-mediated antiviral response. The viral accessory protein ORF6 is localized to lipid droplets, and ORF6 inhibit the host cell interferon response by interacting directly with STAT1. The interplay between the host cell interferon pathway and viral mechanisms to evade interferon signaling is one of the most essential aspects of virus-host interactions. Considering this, we hypothesize that the interaction of SARS-CoV-2 ORF6 and lipid droplets play a role in disrupting the antiviral interferon response. Understanding the relationship between SARS-CoV-2 and lipid droplets will provide new insights about the virus-host interaction.