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GII.2型诺如病毒衣壳基因的遗传分析

Genetic analysis of the capsid gene of genotype GII.2 noroviruses.

作者信息

Iritani Nobuhiro, Vennema Harry, Siebenga J Joukje, Siezen Roland J, Renckens Bernadet, Seto Yoshiyuki, Kaida Atsushi, Koopmans Marion

机构信息

Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands.

出版信息

J Virol. 2008 Aug;82(15):7336-45. doi: 10.1128/JVI.02371-07. Epub 2008 May 14.

Abstract

Noroviruses (NoVs) are considered to be a major cause of acute nonbacterial gastroenteritis in humans. The NoV genus is genetically diverse, and genotype GII.4 has been most commonly identified worldwide in recent years. In this study we analyzed the complete capsid gene of NoV strains belonging to the less prevalent genotype GII.2. We compared a total of 36 complete capsid sequences of GII.2 sequences obtained from the GenBank (n = 5) and from outbreaks or sporadic cases that occurred in The Netherlands (n = 10) and in Osaka City, Japan (n = 21), between 1976 and 2005. Alignment of all capsid sequences did not show fixation of amino acid substitutions over time as an indication for genetic drift. In contrast, when strains previously recognized as recombinants were excluded from the alignment, genetic drift was observed. Substitutions were found at five informative sites (two in the P1 subdomain and three in the P2 subdomain), segregating strains into five genetic groups (1994 to 1997, 1999 to 2000, 2001 to 2003, 2004, and 2005). Only one amino acid position changed consistently between each group (position 345). Homology modeling of the GII.2 capsid protein showed that the five amino acids were located on the surface of the capsid and close to each other at the interface of two monomers. The data suggest that these changes were induced by selective pressure, driving virus evolution. Remarkably, this was observed only for nonrecombinant genomes, suggesting differences in behavior with recombinant strains.

摘要

诺如病毒(NoVs)被认为是人类急性非细菌性胃肠炎的主要病因。诺如病毒属在基因上具有多样性,近年来基因型GII.4在全球范围内最为常见。在本研究中,我们分析了属于较不常见基因型GII.2的诺如病毒株的完整衣壳基因。我们比较了1976年至2005年间从GenBank获得的5条、在荷兰发生的疫情或散发病例中获得的10条以及在日本大阪市发生的疫情或散发病例中获得的21条GII.2序列的总共36条完整衣壳序列。所有衣壳序列的比对未显示氨基酸替换随时间固定,以此作为基因漂移的指标。相反,当从比对中排除先前被认定为重组体的毒株时,观察到了基因漂移。在5个信息位点发现了替换(P1亚结构域中有2个,P2亚结构域中有3个),将毒株分为5个基因群(1994年至1997年、1999年至2000年、2001年至2003年、2004年和2005年)。每组之间只有一个氨基酸位置持续变化(位置345)。GII.2衣壳蛋白的同源建模表明,这5个氨基酸位于衣壳表面,在两个单体的界面处彼此靠近。数据表明,这些变化是由选择压力诱导的,推动了病毒进化。值得注意的是,仅在非重组基因组中观察到这种情况,表明与重组毒株在行为上存在差异。

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