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A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission
Terrence M. Tumpey,1*Taronna R. Maines,1Neal Van Hoeven,1Laurel Glaser,2Alicia Solórzano,2Claudia Pappas,1,2Nancy J. Cox,1David E. Swayne,3Peter Palese,2Jacqueline M. Katz,1Adolfo García-Sastre2
The 1918 influenza pandemic was a catastrophic series of virusoutbreaks that spread across the globe. Here, we show that onlya modest change in the 1918 influenza hemagglutinin receptorbinding site alters the transmissibility of this pandemic virus.Two amino acid mutations that cause a switch in receptor bindingpreference from the human -2,6 to the avian -2,3 sialic acidresulted in a virus incapable of respiratory droplet transmissionbetween ferrets but that maintained its lethality and replicationefficiency in the upper respiratory tract. Furthermore, poortransmission of a 1918 virus with dual -2,6 and -2,3 specificitysuggests that a predominant human -2,6 sialic acid binding preferenceis essential for optimal transmission of this pandemic virus.These findings confirm an essential role of hemagglutinin receptorspecificity for the transmission of influenza viruses amongmammals.
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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