Molecular epidemiology of genogroup II-genotype 4 noroviruses in the United States between 1994 and 2006

Human noroviruses (NoVs) of genogroup II, genotype 4 (GII.4) are the most common strains detected in outbreaks of acute gastroenteritis worldwide. To gain insight into the epidemiology and genetic variation of GII.4 strains, we analyzed 773 NoV outbreaks reported to the CDC from 1994 to 2006. Of these NoV outbreaks, 629 (81.4%) were caused by GII viruses and 342 (44.2%) were caused by GII.4 strains. The proportion of GII.4 outbreaks increased from 5% in 1994 to 85% in 2006, but distinct annual differences were noted, including sharp increases in 1996, 2003, and 2006 each associated with newly emerging GII.4 strains. Sequence analysis of the full-length VP1 gene of GII.4 strains identified in this study and from GenBank segregated these viruses into at least 9 distinct subclusters which had 1.3 to 3.2% amino acid variation between strains in different subclusters. We propose that GII.4 subclusters be defined as having >5% sequence variation between strains. Our data confirm other studies on the rapid emergence and displacement of highly virulent GII.4 strains.