Norovirus interactions with the commensal microbiota

About the Authors: Meagan E. Sullender Affiliation: Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, United States of America ORCID logo http://orcid.org/0000-0001-6666-8650 Megan T. Baldridge * E-mail: mbaldridge@wustl.edu Affiliation: Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, United States of America ORCID logo http://orcid.org/0000-0002-7030-6131 Introduction Human norovirus (HNoV) is the leading cause of epidemic nonbacterial gastroenteritis worldwide, causing an acute diarrheal infection and occasionally chronic infection in immunocompromised individuals. Norovirus pathogenesis is affected by many factors in the enteric environment. a) The presence of commensal bacteria allows for efficient MNoV infection, with tuft cells being one rare cell population infected. b) Absence of commensal bacteria reduces MNoV titers by depleting tuft cell populations and potentially altering innate immune responses during persistent MNoV infection. c) Binding of HNoV to HBGA-positive enteric bacteria has been found to facilitate infection of B cells. d) Sialic acid moieties on the cell surface have been found to act as coreceptors for MNoV infection of macrophages, while bile acids have been found to be important for the establishment of HNoV infection of enterocytes. e) MNoV infection has been found to trigger the expression of IFN-λ in infected cells, up-regulating interferon simulated genes that restrict viral replication and subsequent spread of infection—the mechanism of this process has yet to be characterized, but commensals are believed to play a major regulatory role. The MNoV model system allows for the merging of basic mechanistic principles of infection and replication from cell culture systems to pathogenesis in a host system that is both genetically malleable and affordable. [...]far, MNoV studies have allowed for the elucidation of a species-specific proteinaceous receptor (CD300LF) and viral tropism for a rare intestinal epithelial cell population called tuft cells during persistent infection as well as macrophages, dendritic cells, and lymphocytes during acute infection in vivo [5–7]. In addition to commensal bacteria, parasitic worms (such as Trichinella spiralis) also exhibit a provi