Lipid droplets in the antiviral response via viperin in skeletal muscle cells infected with Chikungunya

• Grant number: 25/05010-1
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: September 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Mariana Kiomy Osako
• Grantee: Beatriz Calasense de Campos
• Supervisor: Mark Harris
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Leeds, England
• Associated to the scholarship: 24/10834-0 - Lipid droplets in the antiviral response via viperin in skeletal muscle cells infected with Chikungunya, BP.MS

Abstract

Chikungunya virus (CHIKV) is an arbovirus that causes acute febrile illness with persistent musculoskeletal symptoms, with no specific treatments or vaccines available. Skeletal muscle plays a key role in disease pathogenesis. Although this tissue infection plays a key role in pathogenesis and sequelae development, few studies have focused on the cellular mechanisms underlying infection in skeletal muscle cells. Viperin, an antiviral protein that localizes with endoplasmic reticulum and lipid droplets (LDs), was shown to inhibit CHIKV replication, and its expression is enhanced after infection in fibroblasts and skeletal muscle cells. As studies has shown that viperin's antiviral properties are closely related to the presence of lipid droplets, our hypothesis is that these organelles are important in establishing an antiviral immune response via viperin. Interestingly, our preliminary data indicate that inducing lipid droplets in myoblasts correlates with reduced viral permissiveness. In addition, recent studies from our collaborators shows that the nsp3 protein of CHIKV is localized close to lipid droplets in hepatic cells. Indeed, our early findings shows the proximity of nsp3 to lipid droplets in myotubes, indicating that the possible roles played by these organelles in CHIKV infection are yet to be uncovered. In this project, we propose to use a non-cytotoxic CHIKV replicon system developed by our collaborators to assess the nsp3-LDs proximity under a context of persistent replication, using super-resolution microscopy and live cell imaging equipment. Additionally, we will generate a viperin knockout C2C12 cell line using CRISPR-Cas9 to evaluate its role in viral replication and LD dynamics. This study aims to elucidate the antiviral potential of LDs and viperin in skeletal muscle, providing novel insights into CHIKV pathogenesis and potential therapeutic targets. (AU)