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Science 2 February 2007:
Vol. 315. no. 5812, pp. 655 - 659
DOI: 10.1126/science.1136212
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Reports

A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission

Terrence M. Tumpey,1* Taronna R. Maines,1 Neal Van Hoeven,1 Laurel Glaser,2 Alicia Solórzano,2 Claudia Pappas,1,2 Nancy J. Cox,1 David E. Swayne,3 Peter Palese,2 Jacqueline M. Katz,1 Adolfo García-Sastre2

The 1918 influenza pandemic was a catastrophic series of virus outbreaks that spread across the globe. Here, we show that only a modest change in the 1918 influenza hemagglutinin receptor binding site alters the transmissibility of this pandemic virus. Two amino acid mutations that cause a switch in receptor binding preference from the human {alpha}-2,6 to the avian {alpha}-2,3 sialic acid resulted in a virus incapable of respiratory droplet transmission between ferrets but that maintained its lethality and replication efficiency in the upper respiratory tract. Furthermore, poor transmission of a 1918 virus with dual {alpha}-2,6 and {alpha}-2,3 specificity suggests that a predominant human {alpha}-2,6 sialic acid binding preference is essential for optimal transmission of this pandemic virus. These findings confirm an essential role of hemagglutinin receptor specificity for the transmission of influenza viruses among mammals.

1 Influenza Branch, Mailstop G-16, Division of Viral and Ricksettial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333, USA.
2 Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
3 Southeast Poultry Research Laboratory, Agricultural Research Laboratory, U.S. Department of Agriculture, 934 College Station Road, Athens, GA 30606, USA.

* To whom correspondence should be addressed. E-mail: tft9{at}cdc.gov

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Science. ISSN 0036-8075 (print), 1095-9203 (online)