Advances in Norovirus Biology

Abstract

Human noroviruses are a major cause of epidemic and sporadic gastroenteritis worldwide, and can chronically infect immunocompromised patients. Efforts to develop effective vaccines and antivirals have been hindered by the uncultivable nature and extreme genetic diversity of human noroviruses. Although they remain a particularly challenging pathogen to study, recent advances in norovirus animal models and in vitro cultivation systems have led to an increased understanding of norovirus molecular biology and replication, pathogenesis, cell tropism, and innate and adaptive immunity. Furthermore, clinical trials of vaccines consisting of nonreplicating virus-like particles have shown promise. In this review, we summarize these recent advances and discuss controversies in the field, which is rapidly progressing towards generation of antiviral agents and increasingly effective vaccines.

Oral Norovirus Infection Is Blocked in Mice Lacking Peyer's Patches and Mature M Cells

“…MNV transmission via the fecal-oral route requires mechanisms for crossing the epithelial barrier from the intestinal lumen into the lamina propria to initiate infection of immune cells (2,40). Possible mechanisms for crossing the barrier include breaking intestinal membrane tight junctions (41), directly infecting intestinal epithelial cells (42), and using transcellular pores (43), dendritic processes (44), and M cells (18).…”

“…N oroviruses (NoVs) are nonenveloped, positive-sense, single-stranded RNA viruses that are transmitted between hosts through the fecal-oral route (1,2). Human noroviruses (HuNoVs) are responsible for around one-fifth of all cases of gastroenteritis worldwide (3).…”

Regulation of Norovirus Virulence by the VP1 Protruding Domain Correlates with B Cell Infection Efficiency

“…Murine NoVs (MuNoVs) are well-established HuNoV surrogates that replicate efficiently in cultured cells and in their natural rodent host (11): MuNoVs infect macrophages, dendritic cells, and B cells in vitro, while they do not infect cultured epithelial cells (9,12). Available evidence supports this cell tropism during in vivo infections as well (9,(12)(13)(14).…”

Identification of a novel cellular target and a co-factor for norovirus infection – B cells & commensal bacteria

“…Regardless, both MuNoVs and HuNoVs can establish prolonged infections associated with extended periods of fecal shedding even during asymptomatic infections. 19 Thus, there must be in vivo reservoir of prolonged or persistent infection which may in fact be intestinal B cells and may be associated with the ability of the viruses to noncytopathically infect this cell type.…”

“…Numerous MuNoV strains have been discovered since 2003 which differ in pathogenicity, persistence establishment, and immune response. 19 Two genetically related but pathogenically distinct MuNoV strains called MNV-1 and MNV-3 were selected for our studies since differences in cell tropism could provide clues regarding the differences in overall infection outcome. Specifically, MNV-1 is more virulent than MNV-3 in wild-type and interferon-deficient mice 20 ; MNV-1 is cleared acutely whereas MNV-3 establishes a persistent infection in the colon 21,22 ; and MNV-3 elicits a more robust protective immune response than MNV-1.…”