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Journal of Virology, November 2008, p. 11247-11262, Vol. 82, No. 22
0022-538X/08/$08.00+0 doi:10.1128/JVI.00897-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Identification of Monomorphic and Divergent Haplotypes in the 2006-2007 Norovirus GII/4 Epidemic Population by Genomewide Tracing of Evolutionary History
Kazushi Motomura,1
Tomoichiro Oka,2
Masaru Yokoyama,1
Hiromi Nakamura,1
Hiromi Mori,1
Hirotaka Ode,1
Grant S. Hansman,2
Kazuhiko Katayama,2
Tadahito Kanda,1
Tomoyuki Tanaka,3
Naokazu Takeda,2
Hironori Sato,1* and the Norovirus Surveillance Group of Japan
Center for Pathogen Genomics, National Institute of Infectious Diseases, Tokyo 208-0011, Japan,1 Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan,2 Sakai City Institute of Public Health, Osaka 590-0953, Japan3
Received 30 April 2008/ Accepted 25 August 2008
Our norovirus (NoV) surveillance group reported a >4-fold increase in NoV infection in Japan during the winter of 2006-2007 compared to the previous winter. Because the increase was not linked to changes in the surveillance system, we suspected the emergence of new NoV GII/4 epidemic variants. To obtain information on viral changes, we conducted full-length genomic analysis. Stool specimens from 55 acute gastroenteritis patients of various ages were collected at 11 sites in Japan between May 2006 and January 2007. Direct sequencing of long PCR products revealed 37 GII/4 genome sequences. Phylogenetic study of viral genome and partial sequences showed that the two new GII/4 variants in Europe, termed 2006a and 2006b, initially coexisted as minorities in early 2006 in Japan and that 2006b alone had dominated over the resident GII/4 variants during 2006. A combination of phylogenetic and entropy analyses revealed for the first time the unique amino acid substitutions in all eight proteins of the new epidemic strains. These data and computer-assisted structural study of the NoV capsid protein are compatible with a model of antigenic drift with tuning of the structure and functions of multiple proteins for the global outgrowth of new GII/4 variants. The availability of comprehensive information on genome sequences and unique protein changes of the recent global epidemic variants will allow studies of diagnostic assays, molecular epidemiology, molecular biology, and adaptive changes of NoV in nature.
* Corresponding author. Mailing address: Center for Pathogen Genomics, National Institute of Infectious Diseases, Gakuen 4-7-1, MusashiMurayama-shi, Tokyo 208-0011, Japan. Phone: (81) 42-5610771. Fax: (81) 42-5675632. E-mail: hirosato{at}nih.go.jp
Published ahead of print on 4 September 2008.
Participants of the Norovirus Surveillance Group of Japan who contributed to this study include Shima Yoshizumi (Hokkaido Institute of Public Health, Hokkaido, Japan), Toshiyuki Mikami (Aomori Institute of Public Health, Aomori, Japan), Hiroyuki Saito (Akita Prefectural Research Center for Public Health and Environment, Akita, Japan), You Ueki (Miyagi Prefectural Institute of Public Health and Environment, Sendai, Japan), Takenori Takizawa (Toyama Institute of Public Health, Toyama, Japan), Kiyoko Uchino (Sakai City Institute of Public Health, Sakai, Osaka, Japan), Mamoru Noda (National Institute of Health Sciences, Tokyo, Japan), Reiko Kondo (Ehime Prefecture Institute of Public Health and Environmental Science, Ehime, Japan), Yumiko Matsuoka (Kumamoto City Institute of Public Health, Kumamoto, Japan), Sadayuki Funatsumaru (Saga Institute of Public Health, Saga, Japan), and Shinichi Kobayashi (Aichi Prefectural Institute of Public Health, Nagoya, Aichi, Japan).
Journal of Virology, November 2008, p. 11247-11262, Vol. 82, No. 22
0022-538X/08/$08.00+0 doi:10.1128/JVI.00897-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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