Abstract Title
Development of Reporter Replicon Systems for Genogroup II Human Noroviruses: Tools for Antiviral Screening and Mechanistic Insight
Presenter
Myra Hosmillo, University of Cambridge
Co-Author(s)
Frédéric Sorgeloos, Armand-Frappier Santé Biotechnologie Research Centre, INRS, Canada
Ian Goodfellow, Division of Virology, Department of Pathology, University of Cambridge, UK
Abstract Category
Prevention & Control (antivirals)
Abstract
Human noroviruses (HuNoVs) are the leading cause of acute viral gastroenteritis worldwide, responsible for a substantial burden of disease across all age groups and settings. Among the norovirus genogroups, Genogroup II (GII) strains have accounted for the majority of outbreaks over the past two decades, owing to their high transmissibility, antigenic variability, and persistence in populations. Despite their epidemiological dominance and clinical importance, the development of replicon or reverse genetics systems for GII HuNoVs has lagged, in part due to their genetic diversity and the inherent difficulties in establishing robust, reproducible cell-based models.
Recent advances in reverse genetics have enabled the development of reporter replicon systems as a practical alternative for investigating norovirus replication. These systems offer a means to screen direct-acting antiviral compounds and interrogate host factors that regulate viral RNA synthesis. Here, we present the design and validation of luciferase-based reporter replicons for GII.1 and GII.4 strains. We detail the strategies employed to optimize their stability and responsiveness, and describe validation workflows using well-characterized inhibitors of norovirus replication.
Our data support the utility of GII reporter replicons as a consistent and scalable platform for compound screening and mechanistic studies. While these systems do not recapitulate the full viral life cycle, they provide a valuable tool for dissecting intracellular replication events and identifying genotype-specific determinants of antiviral susceptibility. These replicons expand the experimental toolkit available for HuNoV research and contribute to ongoing efforts to develop targeted therapeutics and deepen our understanding of norovirus molecular biology.
Recent advances in reverse genetics have enabled the development of reporter replicon systems as a practical alternative for investigating norovirus replication. These systems offer a means to screen direct-acting antiviral compounds and interrogate host factors that regulate viral RNA synthesis. Here, we present the design and validation of luciferase-based reporter replicons for GII.1 and GII.4 strains. We detail the strategies employed to optimize their stability and responsiveness, and describe validation workflows using well-characterized inhibitors of norovirus replication.
Our data support the utility of GII reporter replicons as a consistent and scalable platform for compound screening and mechanistic studies. While these systems do not recapitulate the full viral life cycle, they provide a valuable tool for dissecting intracellular replication events and identifying genotype-specific determinants of antiviral susceptibility. These replicons expand the experimental toolkit available for HuNoV research and contribute to ongoing efforts to develop targeted therapeutics and deepen our understanding of norovirus molecular biology.