Noroviruses—The State of the Art, Nearly Fifty Years after Their Initial Discovery

Abstract

Human noroviruses are recognised as the major global cause of viral gastroenteritis. Here, we provide an overview of notable advances in norovirus research and provide a short recap of the novel model systems to which much of the recent progress is owed. Significant advances include an updated classification system, the description of alternative virus-like protein morphologies and capsid dynamics, and the further elucidation of the functions and roles of various viral proteins. Important milestones include new insights into cell tropism, host and microbial attachment factors and receptors, interactions with the cellular translational apparatus, and viral egress from cells. Noroviruses have been detected in previously unrecognised hosts and detection itself is facilitated by improved analytical techniques. New potential transmission routes and/or viral reservoirs have been proposed. Recent in vivo and in vitro findings have added to the understanding of host immunity in response to norovirus infection, and vaccine development has progressed to preclinical and even clinical trial testing. Ongoing development of therapeutics includes promising direct-acting small molecules and host-factor drugs.

Swine Norovirus: Past, Present, and Future

“…The attachment of norovirus to the cell surface is mediated by the VP1 and carbohydrate cell receptors; in particular, the histoblood group antigens (HBGAs) seem to have a crucial role [ 18 ]. CD300lf, an integral membrane protein containing an immunoglobulin domain, which binds to the P2 subdomain of VP1, mediates the entry into the cell of murine norovirus.…”

“…CD300lf, an integral membrane protein containing an immunoglobulin domain, which binds to the P2 subdomain of VP1, mediates the entry into the cell of murine norovirus. However, the analogous receptor for the other noroviruses and the mechanism of endocytosis is still unknown [ 18 ].…”

“…VPg (NS5) works as a cap and mediates the translation of viral RNA into proteins using the host cell apparatus. ORF1 encodes a polyprotein that is co- and post-translationally cleaved by a viral protease (NS6) to release viral proteins and their precursors (NS1/2 to NS7) [ 18 ]. Subgenomic RNA is expressed at higher levels than genomic RNA; this could be a strategy to increase the production levels of VP1 for the assembly of the virus [ 18 ].…”

“…Viral replication occurs in close association with the rearrangement of intracellular membranes driven by viral proteins NS1/2 and NS4 [ 18 ]. Genome duplication occurs through the synthesis of an intermediate RNA negative sense, which serves as a template for the RNA-dependent RNA-polymerase (RdRp) that synthesises positive sense gRNA and sgRNA [ 4 ].…”

Evaluation of heat inactivation of human norovirus in freshwater clams using human intestinal enteroids

“…Among those, HuNoV is a most frequently detected pathogen in contaminated foods being consumed by ill individuals (WHO, 2015; Lee and Yoon, 2021). Shellfish, especially oysters, are recognized as one of the major sources for HuNoV-associated foodborne disease due to the accumulation of HuNoVs in the digestive gland by filter feeding (Ludwig-Begall et al, 2021).…”