Divergent evolution of norovirus GII/4 by genome recombination from May 2006 to February 2009 in Japan.
Norovirus GII/4 is a leading cause of acute viral gastroenteritis in humans. We examined here how the GII/4 virus evolves to generate and sustain new epidemics in humans, using 199 near-full-length GII/4 genome sequences and 11 genome segment clones from human stool specimens collected at 19 sites in Japan between May 2006 and February 2009. Phylogenetic studies demonstrated outbreaks of 7 monophyletic GII/4 subtypes, among which a single subtype, termed 2006b, had continually predominated. Phylogenetic-tree, bootscanning-plot, and informative-site analyses revealed that 4 of the 7 GII/4 subtypes were mosaics of recently prevalent GII/4 subtypes and 1 was made up of the GII/4 and GII/12 genotypes. Notably, single putative recombination breakpoints with the highest statistical significance were constantly located around the border of open reading frame 1 (ORF1) and ORF2 (P <or= 0.000001), suggesting outgrowth of specific recombinant viruses in the outbreaks. The GII/4 subtypes had many unique amino acids at the time of their outbreaks, especially in the N-term, 3A-like, and capsid proteins. Unique amino acids in the capsids were preferentially positioned on the outer surface loops of the protruding P2 domain and more abundant in the dominant subtypes. These findings suggest that intersubtype genome recombination at the ORF1/2 boundary region is a common mechanism that realizes independent and concurrent changes on the virion surface and in viral replication proteins for the persistence of norovirus GII/4 in human populations.
Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Kazushi
K
Motomura
Masaru
M
Yokoyama
Hirotaka
H
Ode
Hiromi
H
Nakamura
Hiromi
H
Mori
Tadahito
T
Kanda
Tomoichiro
T
Oka
Kazuhiko
K
Katayama
Mamoru
M
Noda
Tomoyuki
T
Tanaka
Naokazu
N
Takeda
Hironori
H
Sato
D017250:Caliciviridae Infections / Q000453:epidemiology* / Q000821:virology; D016000:Cluster Analysis; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D005243:Feces / Q000821:virology; D005759:Gastroenteritis / Q000453:epidemiology* / Q000821:virology; D016679:Genome, Viral; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D029322:Norovirus / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014764:Viral Proteins / Q000235:genetics
D012367:RNA, Viral; D014764:Viral Proteins