Structural and Functional Studies of Influenza Virus A/H6 Hemagglutinin.
Structural and Functional Studies of Influenza Virus A/H6 Hemagglutinin.
复制标题
DOI：
10.1371/journal.pone.0134576
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Ni F;Kondrashkina E;Wang Q
2013年6月，台湾报告首例人感染甲型H6N1禽流感病毒。这一事件引发了人们对可能的人类疫情和H6病毒大流行的担忧。在本研究中，我们对人感染的A/台湾/2/2013(H6N1)(TW H6)病毒和在豚鼠中有效传播的禽流感A/鸡/广东/S1311/2010(H6N6)(GDH6)病毒的血凝素(HA)蛋白进行了结构和功能的研究。我们的结果表明，在HA1 Q226存在的情况下，GDH6 HA中的HA1 S137、E190和G228三联体允许与禽类和人的受体结合，但对禽类受体略有偏爱。它在大多数H6亚型中的保守性为该亚型更广泛的寄主范围提供了解释。此外，TW H6 HA中的N137、V190和S228三联体可能会减轻H2和H3在与类人受体结合时对HA1 226处疏水残基的需求。因此，TW H6 HA对人类受体有轻微的偏好，因此可能代表着人类完全适应的中间产物。重要的是，在过去14年从台湾分离的H6病毒中，有74%的H6病毒中发现了三联体，这表明来自该地区的H6病毒对人类健康的威胁增加。H6 HA的HA1 137、190和228位三联体在与受体结合中的新作用也可能被其他HA亚型用于实现人类适应，这需要在实验室进一步测试和在现场密切监测。
In June 2013, the first human infection by avian influenza A(H6N1) virus was reported in Taiwan. This incident raised the concern for possible human epidemics and pandemics from H6 viruses. In this study, we performed structural and functional investigation on the hemagglutinin (HA) proteins of the human-infecting A/Taiwan/2/2013(H6N1) (TW H6) virus and an avian A/chicken/Guangdong/S1311/2010(H6N6) (GD H6) virus that transmitted efficiently in guinea pigs. Our results revealed that in the presence of HA1 Q226, the triad of HA1 S137, E190 and G228 in GD H6 HA allows the binding to both avian- and human-like receptors with a slight preference for avian receptors. Its conservation among the majority of H6 HAs provides an explanation for the broader host range of this subtype. Furthermore, the triad of N137, V190 and S228 in TW H6 HA may alleviate the requirement for a hydrophobic residue at HA1 226 of H2 and H3 HAs when binding to human-like receptors. Consequently, TW H6 HA has a slight preference for human receptors, thus may represent an intermediate towards a complete human adaptation. Importantly, the triad observed in TW H6 HA is detected in 74% H6 viruses isolated from Taiwan in the past 14 years, suggesting an elevated threat of H6 viruses from this region to human health. The novel roles of the triad at HA1 137, 190 and 228 of H6 HA in binding to receptors revealed here may also be used by other HA subtypes to achieve human adaptation, which needs to be further tested in laboratory and closely monitored in field surveillance.