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

Abstract

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.

Norovirus genotype distribution in outbreaks of acute gastroenteritis among children and older people: an 8-year study

“…The number of outbreaks in these three facilities accounted for approximately 70–80 % of the total NoV outbreaks reported in Yokohama, although the magnitude of outbreaks differed in each facility annually [26]. 76.8 % of the outbreaks in these three facilities occurred in November–February, and the highest prevalence of NoV outbreaks was observed in the winter period.…”

“…Furthermore, especially in K/Ns and NHs, the outbreaks in the 2012–2013 season occurred earlier than in the other seasons. This might have been related to the emergence of a new GII.4 variant (Sydney 2012) [26]. …”

“…The infants attending K/Ns are in closer contact with adults than school children, and GII.4 is the dominant genotype in adult populations [15]. Moreover, several studies confirmed that GI genotypes are present in the environment, although GI genotypes are detected less frequently in clinical samples than GII genotypes [6, 26, 29, 30, 34]. It is thus likely that school children come in contact with various genotypes, including GI genotypes, because school children have a wider sphere of activity than infants.…”

“…GII.2, GII.3, GII.6, and GII.14 were detected throughout Yokohama during this study period [26], and these four genotypes are mainly associated with sporadic infections in children in some Asian countries, including Japan [8, 15, 36, 37]. Genotype-specific herd immunity in infants and young children can last for years and likely influences the endemic NoV genotype(s) in the next season [15].…”

Norovirus drug candidates that inhibit viral capsid attachment to human histo-blood group antigens

“…Understanding the genetic diversity of norovirus is of paramount importance in the design of anti-norovirus strategies. A number of new GII.4 variants (genotypes can be further subdivided into variants) have appeared every two to three years (Kumazaki and Usuku, 2015). Some GII.4 variants such as US95/96, Den Haag 2006b and Sydney 2012 have been recognized as having pandemic potential (Eden et al, 2014).…”