Key Laboratory of Protein & Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
University of the Chinese Academy of Sciences, Beijing, China.
Sci Rep. 2017 Oct 30;7(1):14295. doi: 10.1038/s41598-017-14533-3.
Many host specific mutations have been detected in influenza A viruses (IAVs). However, their effects on hydrogen bond (H-bond) variations have rarely been investigated. In this study, 60 host specific sites were identified in the internal proteins of avian and human IAVs, 27 of which contained mutations with effects on H-bonds. Besides, 30 group specific sites were detected in HA and NA. Twenty-six of 36 mutations existing at these group specific sites caused H-bond loss or formation in at least one subtype. The number of mutations in isolations of 2009 pandemic H1N1, human-infecting H5N1 and H7N9 varied. The combinations of mutations and H-bond changes in these three subtypes of IAVs were also different. In addition, the mutations in isolations of H5N1 distributed more scattered than those in 2009 pandemic H1N1 and H7N9. Eight wave specific mutations in isolations of the fifth H7N9 wave were also identified. Three of them, R140K in HA, Y170H in NA, and R340K in PB2, were capable of resulting in H-bond loss. As mentioned above, these host or group or wave specific H-bond variations provide us with a new field of vision for understanding the changes of structural features in the human adaptation of IAVs.
已在甲型流感病毒 (IAV) 中检测到许多宿主特异性突变。然而，它们对氢键 (H-bond) 变化的影响很少被研究。在这项研究中，在禽源和人源 IAV 的内部蛋白中鉴定出 60 个宿主特异性位点，其中 27 个包含影响 H-bond 的突变。此外，在 HA 和 NA 中还检测到 30 个组特异性位点。在这些组特异性位点存在的 36 个突变中的 26 个导致至少一个亚型的 H-bond 丢失或形成。2009 年大流行 H1N1、感染人类的 H5N1 和 H7N9 的分离株中的突变数量不同。这三种 IAV 中的突变组合和 H-bond 变化也不同。此外，H5N1 分离株中的突变分布比 2009 年大流行 H1N1 和 H7N9 更分散。还鉴定出第五波 H7N9 分离株中的 8 个波特异性突变。其中 3 个，HA 中的 R140K、NA 中的 Y170H 和 PB2 中的 R340K，能够导致 H-bond 丢失。如前所述，这些宿主特异性、组特异性或波特异性的 H-bond 变化为我们提供了一个新的视角，有助于理解 IAV 人类适应过程中结构特征的变化。
