Journal
SCIENCE
Volume 315, Issue 5812, Pages 655-659Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1136212
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Funding
- NIAID NIH HHS [U19 AI62623, P01 AI058113] Funding Source: Medline
- PHS HHS [U54 AIO57158] Funding Source: Medline
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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.
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