Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015
Human norovirus (HuNoV) is a leading cause of viral gastroenteritis worldwide, of which GII.4 is the most predominant genotype. Unlike other genotypes, GII.4 has created various variants that escaped from previously acquired immunity of the host and caused repeated epidemics. However, the molecular...
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Frontiers Media S.A.
2017-12-01
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author | Takumi Motoya Takumi Motoya Koo Nagasawa Yuki Matsushima Noriko Nagata Akihide Ryo Tsuyoshi Sekizuka Akifumi Yamashita Makoto Kuroda Yukio Morita Yoshiyuki Suzuki Nobuya Sasaki Kazuhiko Katayama Hirokazu Kimura Hirokazu Kimura Hirokazu Kimura |
author_facet | Takumi Motoya Takumi Motoya Koo Nagasawa Yuki Matsushima Noriko Nagata Akihide Ryo Tsuyoshi Sekizuka Akifumi Yamashita Makoto Kuroda Yukio Morita Yoshiyuki Suzuki Nobuya Sasaki Kazuhiko Katayama Hirokazu Kimura Hirokazu Kimura Hirokazu Kimura |
author_sort | Takumi Motoya |
collection | DOAJ |
description | Human norovirus (HuNoV) is a leading cause of viral gastroenteritis worldwide, of which GII.4 is the most predominant genotype. Unlike other genotypes, GII.4 has created various variants that escaped from previously acquired immunity of the host and caused repeated epidemics. However, the molecular evolutionary differences among all GII.4 variants, including recently discovered strains, have not been elucidated. Thus, we conducted a series of bioinformatic analyses using numerous, globally collected, full-length GII.4 major capsid (VP1) gene sequences (466 strains) to compare the evolutionary patterns among GII.4 variants. The time-scaled phylogenetic tree constructed using the Bayesian Markov chain Monte Carlo (MCMC) method showed that the common ancestor of the GII.4 VP1 gene diverged from GII.20 in 1840. The GII.4 genotype emerged in 1932, and then formed seven clusters including 14 known variants after 1980. The evolutionary rate of GII.4 strains was estimated to be 7.68 × 10−3 substitutions/site/year. The evolutionary rates probably differed among variants as well as domains [protruding 1 (P1), shell, and P2 domains]. The Osaka 2007 variant strains probably contained more nucleotide substitutions than any other variant. Few conformational epitopes were located in the shell and P1 domains, although most were contained in the P2 domain, which, as previously established, is associated with attachment to host factors and antigenicity. We found that positive selection sites for the whole GII.4 genotype existed in the shell and P1 domains, while Den Haag 2006b, New Orleans 2009, and Sydney 2012 variants were under positive selection in the P2 domain. Amino acid substitutions overlapped with putative epitopes or were located around the epitopes in the P2 domain. The effective population sizes of the present strains increased stepwise for Den Haag 2006b, New Orleans 2009, and Sydney 2012 variants. These results suggest that HuNoV GII.4 rapidly evolved in a few decades, created various variants, and altered its evolutionary rate and antigenicity. |
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spelling | doaj.art-64707d7c8b554dd1ab6af0755cfeaf742022-12-21T19:40:50ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-12-01810.3389/fmicb.2017.02399311964Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015Takumi Motoya0Takumi Motoya1Koo Nagasawa2Yuki Matsushima3Noriko Nagata4Akihide Ryo5Tsuyoshi Sekizuka6Akifumi Yamashita7Makoto Kuroda8Yukio Morita9Yoshiyuki Suzuki10Nobuya Sasaki11Kazuhiko Katayama12Hirokazu Kimura13Hirokazu Kimura14Hirokazu Kimura15Ibaraki Prefectural Institute of Public Health, Mito, JapanLaboratory of Laboratory Animal Science and Medicine, Faculty of Veterinary Medicine, Kitasato University, Towada, JapanInfectious Disease Surveillance Center, National Institute of Infectious Diseases, Musashimurayama, JapanDivision of Virology, Kawasaki City Institute for Public Health, Kawasaki, JapanIbaraki Prefectural Institute of Public Health, Mito, JapanDepartment of Microbiology, Yokohama City University Graduate School of Medicine, Yokohama, JapanPathogen Genomics Center, National Institute of Infectious Diseases, Musashimurayama, JapanPathogen Genomics Center, National Institute of Infectious Diseases, Musashimurayama, JapanPathogen Genomics Center, National Institute of Infectious Diseases, Musashimurayama, JapanDepartment of Food and Nutrition, Tokyo Kasei University, Itabashi-ku, JapanGraduate School of Natural Sciences, Nagoya City University, Nagoya, JapanLaboratory of Laboratory Animal Science and Medicine, Faculty of Veterinary Medicine, Kitasato University, Towada, JapanLaboratory of Viral Infection I, Kitasato Institute for Life Sciences, Kitasato University, Minato-ku, JapanInfectious Disease Surveillance Center, National Institute of Infectious Diseases, Musashimurayama, JapanDepartment of Microbiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan0School of Medical Technology, Faculty of Health Sciences, Gunma Paz University, Takasaki, JapanHuman norovirus (HuNoV) is a leading cause of viral gastroenteritis worldwide, of which GII.4 is the most predominant genotype. Unlike other genotypes, GII.4 has created various variants that escaped from previously acquired immunity of the host and caused repeated epidemics. However, the molecular evolutionary differences among all GII.4 variants, including recently discovered strains, have not been elucidated. Thus, we conducted a series of bioinformatic analyses using numerous, globally collected, full-length GII.4 major capsid (VP1) gene sequences (466 strains) to compare the evolutionary patterns among GII.4 variants. The time-scaled phylogenetic tree constructed using the Bayesian Markov chain Monte Carlo (MCMC) method showed that the common ancestor of the GII.4 VP1 gene diverged from GII.20 in 1840. The GII.4 genotype emerged in 1932, and then formed seven clusters including 14 known variants after 1980. The evolutionary rate of GII.4 strains was estimated to be 7.68 × 10−3 substitutions/site/year. The evolutionary rates probably differed among variants as well as domains [protruding 1 (P1), shell, and P2 domains]. The Osaka 2007 variant strains probably contained more nucleotide substitutions than any other variant. Few conformational epitopes were located in the shell and P1 domains, although most were contained in the P2 domain, which, as previously established, is associated with attachment to host factors and antigenicity. We found that positive selection sites for the whole GII.4 genotype existed in the shell and P1 domains, while Den Haag 2006b, New Orleans 2009, and Sydney 2012 variants were under positive selection in the P2 domain. Amino acid substitutions overlapped with putative epitopes or were located around the epitopes in the P2 domain. The effective population sizes of the present strains increased stepwise for Den Haag 2006b, New Orleans 2009, and Sydney 2012 variants. These results suggest that HuNoV GII.4 rapidly evolved in a few decades, created various variants, and altered its evolutionary rate and antigenicity.http://journal.frontiersin.org/article/10.3389/fmicb.2017.02399/fullbioinformaticsGII.4molecular evolutionNorovirusVP1 |
spellingShingle | Takumi Motoya Takumi Motoya Koo Nagasawa Yuki Matsushima Noriko Nagata Akihide Ryo Tsuyoshi Sekizuka Akifumi Yamashita Makoto Kuroda Yukio Morita Yoshiyuki Suzuki Nobuya Sasaki Kazuhiko Katayama Hirokazu Kimura Hirokazu Kimura Hirokazu Kimura Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015 Frontiers in Microbiology bioinformatics GII.4 molecular evolution Norovirus VP1 |
title | Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015 |
title_full | Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015 |
title_fullStr | Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015 |
title_full_unstemmed | Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015 |
title_short | Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015 |
title_sort | molecular evolution of the vp1 gene in human norovirus gii 4 variants in 1974 2015 |
topic | bioinformatics GII.4 molecular evolution Norovirus VP1 |
url | http://journal.frontiersin.org/article/10.3389/fmicb.2017.02399/full |
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