Wedde Marianne, Biere Barbara, Wolff Thorsten, Schweiger Brunhilde
Division of Influenza Viruses and other Respiratory Viruses, National Reference Centre for Influenza, Robert Koch-Institute, Seestrasse 10, 13353 Berlin, Germany.
Division of Influenza Viruses and other Respiratory Viruses, National Reference Centre for Influenza, Robert Koch-Institute, Seestrasse 10, 13353 Berlin, Germany.
Int J Med Microbiol. 2015 Oct;305(7):762-75. doi: 10.1016/j.ijmm.2015.08.030. Epub 2015 Aug 21.
This report describes the evolution of the influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in Germany between 2008-2009 and 2013-2014. The phylogenetic analysis of the hemagglutinin (HA) genes of both subtypes revealed similar evolution of the HA variants that were also seen worldwide with minor exceptions. The analysis showed seven distinct HA clades for A(H1N1)pdm09 and six HA clades for A(H3N2) viruses. Herald strains of both subtypes appeared sporadically since 2008-2009. Regarding A(H1N1)pdm09, herald strains of HA clade 3 and 4 were detected late in the 2009-2010 season. With respect to A(H3N2), we found herald strains of HA clade 3, 4 and 7 between 2009 and 2012. Those herald strains were predominantly seen for minor and not for major HA clades. Generally, amino acid substitutions were most frequently found in the globular domain, including substitutions near the antigenic sites or the receptor binding site. Differences between both influenza A subtypes were seen with respect to the position of the indicated substitutions in the HA. For A(H1N1)pdm09 viruses, we found more substitutions in the stem region than in the antigenic sites. In contrast, in A(H3N2) viruses most changes were identified in the major antigenic sites and five changes of potential glycosylation sites were identified in the head of the HA monomer. Interestingly, we found in seasons with less influenza activity a relatively high increase of substitutions in the head of the HA in both subtypes. This might be explained by the fact that mutations under negative selection are subsequently compensated by secondary mutations to restore important functions e.g. receptor binding properties. A better knowledge of basic evolution strategies of influenza viruses will contribute to the refinement of predictive mathematical models for identifying novel antigenic drift variants.
本报告描述了2008 - 2009年至2013 - 2014年期间在德国流行的甲型H1N1pdm09和甲型H3N2流感病毒的演变情况。对这两种亚型血凝素（HA）基因的系统发育分析显示，HA变异体的演变情况与全球范围内观察到的相似，仅有一些小的差异。分析显示，甲型H1N1pdm09有七个不同的HA分支，甲型H3N2病毒有六个HA分支。自2008 - 2009年以来，这两种亚型的先驱毒株偶尔出现。对于甲型H1N1pdm09，HA分支3和4的先驱毒株在2009 - 2010季节后期被检测到。对于甲型H3N2，我们在2009年至2012年期间发现了HA分支3、4和7的先驱毒株。这些先驱毒株主要出现在较小的HA分支中，而非主要分支。一般来说，氨基酸替换最常出现在球状结构域，包括抗原位点或受体结合位点附近的替换。两种甲型流感亚型在HA中所示替换位置方面存在差异。对于甲型H1N1pdm09病毒，我们发现茎区的替换比抗原位点更多。相比之下，在甲型H3N2病毒中，大多数变化发生在主要抗原位点，并且在HA单体头部发现了五个潜在糖基化位点的变化。有趣的是，我们发现在流感活动较少的季节，两种亚型HA头部的替换相对增加较多。这可能是由于负选择下的突变随后被二次突变补偿以恢复重要功能，例如受体结合特性。更好地了解流感病毒的基本进化策略将有助于完善用于识别新型抗原漂移变异体的预测数学模型。
