Addition of Glycosylation to Influenza A Virus Hemagglutinin Modulates Antibody-Mediated Recognition of H1N1 2009 Pandemic Viruses
Addition of Glycosylation to Influenza A Virus Hemagglutinin Modulates Antibody-Mediated Recognition of H1N1 2009 Pandemic Viruses
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DOI：
10.4049/jimmunol.1202433
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发表时间：
2013-03-01
影响因子：
4.4
通讯作者：
Reading, Patrick C.
中科院分区：
文献类型：
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作者：
Job, Emma R.;Deng, Yi-Mo;Reading, Patrick C.
季节性甲型流感病毒（IAV）起源于大流行性流感病毒，并经历了抗原结构的变化，包括向病毒血凝素（HA）添加聚糖。HA头部的聚糖通过屏蔽抗原位点促进病毒存活，但高度糖基化的季节性IAV被先天免疫系统的可溶性凝集素灭活。2009年，H1N1大流行人类毒株[A(H1N1)pdm]在HA头部表达一个单糖基化位点（Asn(104)）。从那时起，已经检测到具有额外糖基化位点的变异，并且这些位点的位置与最近的季节性H1N1毒株不同。我们比较了野生型和反向工程的A(H1N1)pdm IAV，它们在HA上具有不同的潜在糖基化位点，对收集抗体和中和抗体的敏感性。向A(H1N1)pdm HA添加聚糖（Asn(136)）与对中和抗体的抗性相关，但没有增加对收集抗体的敏感性。此外，表达Asn（136）的变体在接种甲型H1N1 pdm的小鼠中表现出增强的生长，这与体内逃避抗体介导的免疫一致。因此，HA糖基化的最佳模式存在一个微妙的平衡，以促进逃避抗体介导的免疫，同时保持对凝集素介导的先天免疫系统防御的抵抗力。中华免疫学杂志，2013,19(2):369 - 377。
Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the viral hemagglutinin (HA). Glycans on the head of HA promote virus survival by shielding antigenic sites, but highly glycosylated seasonal IAV are inactivated by soluble lectins of the innate immune system. In 2009, human strains of pandemic H1N1 [A(H1N1)pdm] expressed a single glycosylation site (Asn(104)) on the head of HA. Since then, variants with additional glycosylation sites have been detected, and the location of these sites has been distinct to those of recent seasonal H1N1 strains. We have compared wild-type and reverse-engineered A(H1N1) pdm IAV with differing potential glycosylation sites on HA for sensitivity to collectins and to neutralizing Abs. Addition of a glycan (Asn(136)) to A(H1N1)pdm HA was associated with resistance to neutralizing Abs but did not increase sensitivity to collectins. Moreover, variants expressing Asn(136) showed enhanced growth in A(H1N1)pdm-vaccinated mice, consistent with evasion of Ab-mediated immunity in vivo. Thus, a fine balance exists regarding the optimal pattern of HA glycosylation to facilitate evasion of Ab-mediated immunity while maintaining resistance to lectin-mediated defenses of the innate immune system. The Journal of Immunology, 2013, 190: 2169-2177.