Identification of antinorovirus genes in human cells using genome-wide CRISPR activation screening

Robert C. Orchard, Washington University School of Medicine in St. Louis
Meagan E. Sullender, Washington University School of Medicine in St. Louis
Bria F. Dunlap, Washington University School of Medicine in St. Louis
Dale R. Balce, Washington University School of Medicine in St. Louis
John G. Doench, Washington University School of Medicine in St. Louis
Herbert W. Virgin, Washington University School of Medicine in St. Louis

Abstract

Noroviruses (NoVs) are a leading cause of gastroenteritis worldwide, yet host factors that restrict NoV replication are not well understood. Here, we use a CRISPR activation genome-wide screening to identify host genes that can inhibit murine norovirus (MNoV) replication in human cells. Our screens identified with high confidence 49 genes that can inhibit MNoV infection when overexpressed. A significant number of these genes are in interferon and immune regulation signaling networks, but surprisingly, the majority of the genes identified are neither associated with innate or adaptive immunity nor associated with any antiviral activity. Confirmatory studies of eight of the genes validate the initial screening data. Mechanistic studies on