Tzarum Netanel, McBride Ryan, Nycholat Corwin M, Peng Wenjie, Paulson James C, Wilson Ian A
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.
J Virol. 2017 May 26;91(12). doi: 10.1128/JVI.00046-17. Print 2017 Jun 15.
Influenza A H15 viruses are members of a subgroup (H7-H10-H15) of group 2 hemagglutinin (HA) subtypes that include H7N9 and H10N8 viruses that were isolated from humans during 2013. The isolation of avian H15 viruses is, however, quite rare and, until recently, geographically restricted to wild shorebirds and waterfowl in Australia. The HAs of H15 viruses contain an insertion in the 150-loop (loop beginning at position 150) of the receptor-binding site common to this subgroup and a unique insertion in the 260-loop compared to any other subtype. Here, we show that the H15 HA has a high preference for avian receptor analogs by glycan array analyses. The H15 HA crystal structure reveals that it is structurally closest to H7N9 HA, but the head domain of the H15 trimer is wider than all other HAs due to a tilt and opening of the HA1 subunits of the head domain. The extended 150-loop of the H15 HA retains the conserved conformation as in H7 and H10 HAs. Furthermore, the elongated 260-loop increases the exposed HA surface and can contribute to antigenic variation in H15 HAs. Since avian-origin H15 HA viruses have been shown to cause enhanced disease in mammalian models, further characterization and immune surveillance of H15 viruses are warranted. In the last 2 decades, an apparent increase has been reported for cases of human infection by emerging avian influenza A virus subtypes, including H7N9 and H10N8 viruses isolated during 2013. H15 is the other member of the subgroup of influenza A virus group 2 hemagglutinins (HAs) that also include H7 and H10. H15 viruses have been restricted to Australia, but recent isolation of H15 viruses in western Siberia suggests that they could be spread more globally via the avian flyways that converge and emanate from this region. Here we report on characterization of the three-dimensional structure and receptor specificity of the H15 hemagglutinin, revealing distinct features and specificities that can aid in global surveillance of such viruses for potential spread and emerging threat to the human population.
甲型H15流感病毒是第2组血凝素（HA）亚型的一个亚组（H7-H10-H15）的成员，该亚组包括2013年从人类中分离出的H7N9和H10N8病毒。然而，禽源H15病毒的分离相当罕见，直到最近，在地理上仅限于澳大利亚的野生滨鸟和水禽。H15病毒的HA在该亚组共有的受体结合位点的150环（从第150位开始的环）中有一个插入，与任何其他亚型相比，在260环中有一个独特的插入。在这里，我们通过聚糖阵列分析表明，H15 HA对禽源受体类似物有高度偏好。H15 HA晶体结构表明，它在结构上最接近H7N9 HA，但由于头部结构域的HA1亚基倾斜和打开，H15三聚体的头部结构域比所有其他HA更宽。H15 HA延伸的150环保留了与H7和H10 HA中相同的保守构象。此外，拉长的260环增加了HA的暴露表面，并可能导致H15 HA的抗原变异。由于禽源H15 HA病毒已被证明在哺乳动物模型中会导致病情加重，因此有必要对H15病毒进行进一步的特征描述和免疫监测。在过去20年中，据报道，包括2013年分离出的H7N9和H10N8病毒在内的新型甲型禽流感病毒亚型导致的人类感染病例明显增加。H15是甲型流感病毒第2组血凝素（HA）亚组的另一个成员，该亚组还包括H7和H10。H15病毒一直局限于澳大利亚，但最近在西西伯利亚分离出H15病毒表明，它们可能通过汇聚并发源于该地区的鸟类迁徙路线在全球范围内传播。在这里，我们报告了H15血凝素的三维结构和受体特异性的特征描述，揭示了不同的特征和特异性，这有助于对这类病毒进行全球监测，以防范其潜在传播和对人类群体的新威胁。
