过去的流感大流行始于进化成能够识别并与人类细胞结合的禽流感病毒。然而，科学家仍然不清楚这些病毒如何在物种之间迁移，因为鸟类和人类拥有不同的血凝素蛋白受体，即流感病毒在感染的时候与宿主细胞结合的部分。
Steve Gamblin及其同事发现了一些禽流感病毒由于与人类受体结合的潜力而比其他一些毒株可能更容易在人类身上立足。这组作者使用X射线晶体学确定了1957年“亚洲”大流行流感的H2 血凝素蛋白的结构，并把它与1918年“西班牙”流感的H1血凝素蛋白和1968年的“香港”大流行流感的H3血凝素蛋白进行了比较。
这组科学家还分析了来自禽流感病毒的血凝素蛋白，它们可能是H2大流行病毒的前体，而且证明了这些病毒不需要突变就可以与人类受体结合。一旦进入人体，快速增长的突变可以改善该病毒与人类受体相结合的能力。这些突变还可能应对那些在人类呼吸道中阻断感染的化合物。这组作者说，该研究可能有助于表明哪一种禽流感病毒具有与人类受体相结合的倾向，而且可能造福流感大流行的规划。（生物谷Bioon）
生物谷推荐原始出处：
PNAS September 28, 2009, doi: 10.1073/pnas.0906849106
Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957
Junfeng Liua, David J. Stevensa, Lesley F. Hairea, Philip A. Walkera, Peter J. Coombsa, Rupert J. Russellb, Steven J. Gamblina,1 and John J. Skehela,1
aMRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom; and
bInterdisciplinary Centre for Human and Avian Influenza Research, School of Biology, University of St. Andrews, Fife KY16 9ST, United Kingdom
The viruses that caused the three influenza pandemics of the twentieth century in 1918, 1957, and 1968 had distinct hemagglutinin receptor binding glycoproteins that had evolved the capacity to recognize human cell receptors. We have determined the structure of the H2 hemagglutinin from the second pandemic, the “Asian Influenza” of 1957. We compare it with the 1918 “Spanish Influenza” hemagglutinin, H1, and the 1968 “Hong Kong Influenza” hemagglutinin, H3, and show that despite its close overall structural similarity to H1, and its more distant relationship to H3, the H2 receptor binding site is closely related to that of H3 hemagglutinin. By analyzing hemagglutinins of potential H2 avian precursors of the pandemic virus, we show that the human receptor can be bound by avian hemagglutinins that lack the human–specific mutations of H2 and H3 pandemic viruses, Gln-226Leu, and Gly-228Ser. We show how Gln-226 in the avian H2 receptor binding site, together with Asn-186, form hydrogen bond networks through bound water molecules to mediate binding to human receptor. We show that the human receptor adopts a very similar conformation in both human and avian hemagglutinin-receptor complexes. We also show that Leu-226 in the receptor binding site of human virus hemagglutinins creates a hydrophobic environment near the Sia-1-Gal-2 glycosidic linkage that favors binding of the human receptor and is unfavorable for avian receptor binding. We consider the significance for the development of pandemics, of the existence of avian viruses that can bind to both avian and human receptors.
