Changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic H1N1 influenza virus.
The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. While it has been shown that acquisition of the neuraminidase (NA) and matrix (M) gene segments from a Eurasian-lineage swine virus was required for airborne transmission of the 2009 pandemic H1N1 virus (H1N1pdm09), we show here that an arginine to lysine change in the hemagglutinin (HA) was also necessary. This change at position 149 was distal to the receptor binding site but affected virus-receptor affinity and HA dynamics, allowing the virus to replicate more efficiently in nasal turbinate epithelium and subsequently transmit between ferrets. Receptor affinity should be considered as a factor limiting swine virus spread in humans.
1] Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA [2] Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
Sun-Woo
SW
Yoon
Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel-Aviv 69978, Israel.
Noam
N
Chen
1] Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA [2] INRA, UMR1225, IHAP, F-31076 Toulouse, France.
Mariette F
MF
Ducatez
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ryan
R
McBride
Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Subrata
S
Barman
Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Thomas P
TP
Fabrizio
Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Robert G
RG
Webster
Polymer Research Center and Chemical Engineering Department, Bogazici University, Bebek, Istanbul 34470, Turkey.
Turkan
T
Haliloglu
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
James C
JC
Paulson
Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Charles J
CJ
Russell
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Tomer
T
Hertz
Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel-Aviv 69978, Israel.
Nir
N
Ben-Tal
Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Richard J
RJ
Webby
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000235:genetics; D005289:Ferrets / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity; D007251:Influenza, Human / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008239:Lysine / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014779:Virus Replication / Q000235:genetics
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; D001120:Arginine; D008239:Lysine