Variability in H9N2 haemagglutinin receptor-binding preference and the pH of fusion.
Variability in H9N2 haemagglutinin receptor-binding preference and the pH of fusion.
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DOI：
10.1038/emi.2016.139
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发表时间：
2017-03-22
影响因子：
13.2
通讯作者：
Iqbal M
中科院分区：
文献类型：
--
作者：
Peacock TP;Benton DJ;Sadeyen JR;Chang P;Sealy JE;Bryant JE;Martin SR;Shelton H;McCauley JW;Barclay WS;Iqbal M
H9N2禽流感病毒主要是一种家禽疾病；然而，它们偶尔会感染人类，被认为是潜在的大流行威胁。很少有研究评估H9N2病毒与人畜共患潜能相关的内在生化特性。因此，本研究的目的是研究H9N2血凝素（HAs）使用两个众所周知的人类适应相关因素：受体结合亲和力和融合pH。采用生物层干涉法测定病毒与人和鸟样受体类似物的结合，并通过不同pH值的病毒感染细胞的合胞体形成来测定融合的pH值。我们鉴定了人畜共患G1谱系的当代H9N2病毒，以及人畜共患BJ94谱系的代表性病毒。我们发现，大多数现代H9N2病毒对硫酸酸化的鸟样受体类似物表现出偏好。然而，“东方”G1 H9N2病毒表现出与人类类似受体类似物结合的一致偏好。我们证明亮氨酸在HA受体结合位点226位的存在与与类人唾液酸受体的结合能力相关性较差。H9N2的融合pH值也表现出变异性，在pH值5.4和5.85之间，这与人类H1N1pdm09病毒的第一波相似，但低于人畜共患的H5N1和H7N9病毒的融合pH值。我们的研究结果提示了可能的分子机制，可能是特定H9N2病毒谱系相对较高的人畜共患感染流行率的基础。
H9N2 avian influenza viruses are primarily a disease of poultry; however, they occasionally infect humans and are considered a potential pandemic threat. Little work has been performed to assess the intrinsic biochemical properties related to zoonotic potential of H9N2 viruses. The objective of this study, therefore, was to investigate H9N2 haemagglutinins (HAs) using two well-known correlates for human adaption: receptor-binding avidity and pH of fusion. Receptor binding was characterized using bio-layer interferometry to measure virus binding to human and avian-like receptor analogues and the pH of fusion was assayed by syncytium formation in virus-infected cells at different pHs. We characterized contemporary H9N2 viruses of the zoonotic G1 lineage, as well as representative viruses of the zoonotic BJ94 lineage. We found that most contemporary H9N2 viruses show a preference for sulphated avian-like receptor analogues. However, the ‘Eastern' G1 H9N2 viruses displayed a consistent preference in binding to a human-like receptor analogue. We demonstrate that the presence of leucine at position 226 of the HA receptor-binding site correlated poorly with the ability to bind a human-like sialic acid receptor. H9N2 HAs also display variability in their pH of fusion, ranging between pH 5.4 and 5.85 which is similar to that of the first wave of human H1N1pdm09 viruses but lower than the pH of fusion seen in zoonotic H5N1 and H7N9 viruses. Our results suggest possible molecular mechanisms that may underlie the relatively high prevalence of human zoonotic infection by particular H9N2 virus lineages.