Genetic Analysis of Norovirus GII.4 Variant Strains Detected in Outbreaks of Gastroenteritis in Yokohama, Japan, from the 2006-2007 to the 2013-2014 Seasons

Noroviruses (NoVs) are the leading cause of acute gastroenteritis, both in sporadic cases and outbreaks. Since the 1990s, the emergence of several GII.4 variants has been reported worldwide. To investigate the epidemic status of NoV, 6,724 stool samples collected from outbreaks in Yokohama, Japan, from the 2006-2007 to 2013-2014 seasons were assessed for NoVs. We genotyped one specimen from each GII outbreak and conducted a sequence analysis of the VP1 gene for several GII.4 strains. Of the 947 NoV outbreaks during our study, GII was detected in 835, and GII.4 was the predominant genotype of GII. Five different GII.4 variants, Yerseke 2006a, Den Haag 2006b (2006b), Apeldoorn 2007, New Orleans 2009, and Sydney 2012, were detected. During this study period, the most prevalent variant of GII.4 was 2006b, and in each individual season, either 2006b or Sydney 2012 was the predominant variant. Out of the 16 detected 2006b strains, 12 had some amino acid substitutions in their blockade epitope, and these substitutions were concentrated in three residues. Two of the 2006b strains detected in the 2012-2013 season had a S368E substitution, which is consistent with the amino acid residues at same site of NSW0514 (Sydney 2012 prototype). Among the 16 detected strains of Sydney 2012, a phylogenetic analysis showed that all five strains detected in Yokohama during the 2011-2012 season clustered away from the other Sydney 2012 strains that were detected in the 2012-2013 and 2013-2014 seasons. These five strains and other Sydney 2012 strains in Yokohama had a few amino acid differences in the blockade epitopes compared with NSW0514. The amino acid substitutions observed in this study provide informative data about the evolution of a novel GII.4 variant.