Unravelling the networks that determine and control norovirus infection and pathogenesis.

A single viral strain, GII.4, has dominated norovirus outbreaks for the past 15 years, and this project aims to find out why. Norovirus is the leading cause of acute gastroenteritis worldwide, causing vomiting and diarrhoea. There is no vaccine and no specific treatment. The researchers want to understand the molecular machinery that makes pandemic strains so successful, focusing on the viral RNA polymerase—the enzyme that copies the virus’s genetic material. Preliminary work suggests this enzyme is more error-prone and more active in pandemic strains than in non-pandemic ones. The team will sequence norovirus evolution in human populations to identify “pandemic signature” mutations, then test how those mutations affect replication and disease. They will also use proteomics to map how the virus hijacks host cells, and screen for small molecule inhibitors that block those pathways. A separate line of work targets the host cell’s RNA quality control pathway, which early data suggests could be a promising therapeutic target. If successful, this fundamental science could reveal new vaccine strategies and identify drug targets for a virus that currently has no specific countermeasures. Understanding why one strain dominates may also help predict future pandemic emergence.