Project 10
Involvement of sphingolipids in coronavirus replication
John Ziebuhr
Coronaviruses are known to manipulate cellular lipid homeostasis in order to enable and/or optimize their replication in specific cell types. Sphingolipids (SLs), as key membrane components, are thought to be involved in different steps of the viral replication cycle, such as virus entry and formation of replicative organelles (RO) at which viral RNA synthesis takes place. ROs are cytoplasmic membranous microenvironments that are induced by specific viral transmembrane proteins and their production is thought to involve specific lipids and cellular enzymes. To date, the lipid composition and biogenesis of coronavirus-induced ROs is not well understood. To fill these knowledge gaps, the project aims to identify (sphingo)lipids and lipid metabolizing enzymes that have a role in coronavirus replication. Specifically, the project seeks to
- compare the lipid profiles of CoV-infected cells at different time points post infection
- determine the role of neutral sphingomyelinase and sphingolipids in coronavirus entry into cells and virus-induced RO formation
- characterize the lipid composition of CoV-induced ROs isolated from infected cells
Data arising from this study are expected to reveal potential targets for antiviral drugs effective against human and animal coronaviruses of medical/veterinary importance, such as SARS-CoV-2, MERS-CoV and TGEV.
