title: Evolutionary Constraints on the Norovirus Pandemic Variant GII.4_2006b over the Five-Year Persistence in Japan.
abstract: Norovirus GII.4 is a major cause of global outbreaks of viral gastroenteritis in humans, and has evolved by antigenic changes under the constantly changing human herd immunity. Major shift in the pandemic GII.4 strain periodically occurs concomitant with changes in the antigenic capsid protein VP1. However, how the newly emerged strain evolves after the onset of pandemic remains unclear. To address this issue, we examined molecular evolution of a pandemic lineage, termed the GII.4_2006b, by using the full-length viral genome and VP1 sequences (n= 317) from stools collected at 20 sites in Japan between 2006 and 2011. Phylogenetic tree showed a radial diversification of the genome sequences of GII.4_2006b, suggesting a rapid genetic diversification of the GII.4_2006b population from a few ancestral variants. Impressively, amino acid sequences of the variable VP1 in given seasons remained as homogeneous as those of viral enzymes under annual increase in the nucleotide diversity in the VP1 coding region. The Hamming distances between the earliest and subsequent variants indicate strong constraints on amino acid changes even for the highly variable P2 subdomain. These results show the presence of evolutionary constraints on the VP1 protein and viral enzymes, and suggest that these proteins gain near maximal levels of fitness benefits in humans around the onset of the outbreaks. These findings have implications for our understanding of molecular evolution, mechanisms of the periodic shifts in the pandemic NoV GII.4 strains, and control of the NoV GII.4 pandemic strain.
authors.affiliation: Pathogen Genomics Center, National Institute of Infectious Diseases Tokyo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Sato
authors.affiliation: Pathogen Genomics Center, National Institute of Infectious Diseases Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Pathogen Genomics Center, National Institute of Infectious Diseases Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases Tokyo, Japan.
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Oka
authors.affiliation: Department of Virology II, National Institute of Infectious DiseasesTokyo, Japan; Graduate School of Infection Control Sciences, Kitasato UniversityTokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Katayama
authors.affiliation: Research Institute for Microbial Diseases, Osaka UniversityOsaka, Japan; Thailand-Japan Research Collaboration Center on Emerging and Re-emerging InfectionsNonthaburi, Thailand.
authors.forename: Naokazu
authors.initials: N
authors.lastname: Takeda
authors.affiliation: National Institute of Health Sciences Tokyo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Noda
authors.affiliation: Sakai City Institute of Public Health Osaka, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Pathogen Genomics Center, National Institute of Infectious DiseasesTokyo, Japan; Research Institute for Microbial Diseases, Osaka UniversityOsaka, Japan; Thailand-Japan Research Collaboration Center on Emerging and Re-emerging InfectionsNonthaburi, Thailand.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Motomura
keywords: GII.4; capsid; evolutionary constraints; molecular evolution; norovirus; pandemic strain