Unexpected roles for lipids in promoting murine norovirus binding and entry

Robert Orchard, University of Texas Southwestern Medical Center

Stewart BM, Pierce LR, Olson MO, Baggett NS, Orchard RC Affiliation Departments of Immunology and Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America

Entry and Replication

All viruses must cross the plasma membrane in order to establish an infection. Research efforts have largely focused on how receptors enable viruses to cross membranes. In contrast, very little is known about how lipids regulate viral entry. We have been investigating host factors that regulate norovirus (NoV) replication using the model virus Murine Norovirus (MNV). Using both loss-of-function and gain-of-function genetic screens we have uncovered an unexpected connection between lipids and MNV entry. For example, we have recently determined that the asymmetric distribution of lipids is important for MNV infection of cells and mice. Additionally, we have uncovered an antiviral genes that alter lipid homeostasis. We present a model in which the lipid composition of the plasma membrane represents an unexpected norovirus-host interaction with implications on viral tropism and pathogenesis.