A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission

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

Research output: Contribution to journalArticlepeer-review

490 Scopus citations

Abstract

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 α-2,6 to the avian α-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 α-2,6 and α-2,3 specificity suggests that a predominant human α-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.

Original languageEnglish
Pages (from-to)655-659
Number of pages5
JournalScience
Volume315
Issue number5812
DOIs
StatePublished - 2 Feb 2007

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