Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic.
Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic.
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DOI：
10.1186/s12879-016-1738-1
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发表时间：
2016-08-08
影响因子：
3.7
通讯作者：
Saito M
中科院分区：
文献类型：
--
作者：
Ushirogawa H;Naito T;Tokunaga H;Tanaka T;Nakano T;Terada K;Ohuchi M;Saito M
季节性流行的H1N1和H3N2型甲型流感病毒是通过抗原漂移进化而来的，这种进化导致血凝素(HA)球状头部天冬酰胺(N)连接的糖基化位点(NGSS)的获得，从而影响其抗原和受体结合特性以及毒力。一项流行病学调查表明，尽管传统的季节性H1N1毒株已经消失，但在2009年H1N1大流行之后的几个季节(2010-11和2011-12)，H3N1再次成为主要流行毒株。有趣的是，尽管2009年大流行的H1N1毒株(H1N1pdm09)缺乏额外的NGSS，但在这些季节获得的临床分离的H3N1毒株在HA的第45和144位获得了N(ASN)残留物，形成了额外的NGSS。为了研究这些NGSS是否与H3N2在亚型中的重新出现有关，我们使用添加或不添加NGSS的H3N2毒株的抗血清，测试了氨基酸替换对中和活性的影响。此外，由于HA第144位的N残基被确定为2011-2012年疫苗和流行毒株之间的错配部位，我们通过反向遗传学产生了突变病毒，并通过小鼠鼻腔接种测试了这种特殊的NGS对抗体介导的中和作用的重要性。结果表明，第144位氨基酸替换显著影响中和活性，表现为逃逸突变。我们的数据表明，在HA球状头部新获得的NGSS可能通过帮助逃避体液免疫而在地方性季节性H3N1毒株的重新出现中发挥重要作用。
Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010–11 and 2011–12) immediately following the H1N1 pandemic of 2009. Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011–2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. The results indicated that amino acid substitution at residue 144 significantly affected neutralization activity, acting as an escape mutation. Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity.