LPS and IL-4 Stimulation Favor Murine Norovirus Infection of B Cells

Abstract

Noroviruses are single-stranded positive-polarity RNA viruses classified in the family Caliciviridae. Human noroviruses (HuNoVs) are a leading cause of acute viral gastroenteritis worldwide. Despite their ability to infect various epithelial and nonepithelial cell types, establishing robust in vitro culture systems for HuNoVs remains challenging. As a result, murine norovirus 1 (MNV-1) has become a widely used model for investigating norovirus biology and pathogenesis, due to its ability to replicate efficiently in primary dendritic cells and macrophages. Although different B-cell lines are susceptible to MNV-1 infection, the susceptibility of primary B lymphocytes has been poorly characterized. Here, we demonstrate that MNV-1 infects primary B lymphocytes, with infection levels increased by prior stimulation with lipopolysaccharide and interleukin-4. The enhanced infection does not appear to result from increased virion binding but instead to an increased cellular permissiveness. These findings provide new insights into the cellular tropism of MNV-1 and suggest that the activation status of B-cell influences their susceptibility to infection. This model may improve our understanding of norovirus–host-cell interactions in adaptive immune cells and could aid in the development of more representative in vitro systems for studying norovirus pathogenesis.