過去的流感大流行始于進(jìn)化成能夠識別并與人類細(xì)胞結(jié)合的禽流感病毒,。然而,，科學(xué)家仍然不清楚這些病毒如何在物種之間遷移,，因?yàn)轼B類和人類擁有不同的血凝素蛋白受體,，即流感病毒在感染的時候與宿主細(xì)胞結(jié)合的部分,。
Steve Gamblin及其同事發(fā)現(xiàn)了一些禽流感病毒由于與人類受體結(jié)合的潛力而比其他一些毒株可能更容易在人類身上立足,。這組作者使用X射線晶體學(xué)確定了1957年“亞洲”大流行流感的H2 血凝素蛋白的結(jié)構(gòu)，并把它與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血凝素蛋白進(jìn)行了比較,。
這組科學(xué)家還分析了來自禽流感病毒的血凝素蛋白,，它們可能是H2大流行病毒的前體，而且證明了這些病毒不需要突變就可以與人類受體結(jié)合,。一旦進(jìn)入人體,，快速增長的突變可以改善該病毒與人類受體相結(jié)合的能力。這些突變還可能應(yīng)對那些在人類呼吸道中阻斷感染的化合物,。這組作者說,，該研究可能有助于表明哪一種禽流感病毒具有與人類受體相結(jié)合的傾向，而且可能造福流感大流行的規(guī)劃,。（生物谷Bioon）
生物谷推薦原始出處：
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.
