Genome Diversity and Host Interaction of Noroviruses

The epidemic and sporadic forms of gastroenteritis are common causes of morbidity in developed countries and of morbidity and mortality in developing countries. Although the current review focuses on viral causes of acute gastroenteritis, it can also be caused by bacteria or parasites. Recent studies employing molecular and antigenic methods for detection of enteric viruses showed that the majority of acute viral gastroenteritis cases worldwide are caused by noroviruses (NVs). The molecular cloning and genomic characterization of other viral strains has greatly facilitated our understanding of the genetic structure and classification of NVs. The RNA genome is organized into three open reading frames (ORFs). Several studies were undertaken in recent years to improve understanding of the mechanisms and biological advantages of genotype GII.4 epidemic strains. A study showed that GII.4 NVs evolve stepwise by highly significant preferential accumulation and fixation of nucleotide and amino acid mutations in the protruding part of the capsid protein. Another study showed that the NV capsid protein accumulates mutations more rapidly in healthy immunocompetent individuals than in immunocompromised individuals. In this study, 66 P2 sequences from viruses isolated during outbreaks occurring between 1997 and 2006 in the United Kingdom showed diversity of up to 20%. Further high-resolution structural studies are necessary to determine the role of the P2 subdomain in host interactions and to understand its possible role in NV strain diversity.