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 ias having > 5% sequence variation between strains. Our data confirm other studies on the rapid emergence and displacement of highly virulent GII. 4 strains.