Motomura Kazushi, Yokoyama Masaru, Oka Tomoichiro, Katayama Kazuhiko, Noda Mamoru, Tanaka Tomoyuki, Sato Hironori
Pathogen Genomics Center, National Institute of Infectious Diseases.
Kansenshogaku Zasshi. 2012 Sep;86(5):563-8. doi: 10.11150/kansenshogakuzasshi.86.563.
Norovirus GII.4 is a major etiological agent of acute viral gastroenteritis worldwide. We examined GII.4 evolution using 277 near-full-length GII.4 genome sequences from human stool specimens collected at 20 sites in Japan between May 2006 and March 2010. We found outbreaks of 8 monophyletic GII.4 subtypes, among which a single subtype, termed 2006b, had continually predominated (222/277: 80.7%). Four of the 8 GII.4 subtypes were chimera viruses of recently prevalent GII.4 subtypes. Notably, single putative recombination breakpoints with the highest statistical significance were constantly located around the border of open reading frame 1 (ORF) 1 and ORF 2 (P<0.0001), 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 capsid were preferentially positioned on the outer surface loops of the protruding P2 domain. These data and computer-assisted structural study of NoV capsid protein are compatible with a model of antigenic drift with tuning of the structure-functions of multiple proteins for the survival strategy of GII.4 2006b variant.
诺如病毒GII.4是全球急性病毒性肠胃炎的主要病原体。我们利用2006年5月至2010年3月间在日本20个地点采集的人类粪便标本中的277个近乎全长的GII.4基因组序列，研究了GII.4的进化情况。我们发现了8个单系GII.4亚型的暴发，其中一个名为2006b的亚型持续占据主导地位（222/277：80.7%）。8个GII.4亚型中有4个是近期流行的GII.4亚型的嵌合病毒。值得注意的是，具有最高统计学意义的单个推定重组断点始终位于开放阅读框1（ORF）1和ORF 2的边界附近（P<0.0001），这表明在暴发中特定重组病毒的出现。GII.4亚型在暴发时具有许多独特的氨基酸，特别是在N端、3A样蛋白和衣壳蛋白中。衣壳中的独特氨基酸优先位于突出P2结构域的外表面环上。这些数据以及对诺如病毒衣壳蛋白的计算机辅助结构研究与抗原漂移模型相符，该模型通过调整多种蛋白质的结构功能来实现GII.4 2006b变体的生存策略。
