Amino acid 226 in the hemagglutinin of H4N6 influenza virus determines binding affinity for alpha2,6-linked sialic acid and infectivity levels in primary swine and human respiratory epithelial cells.
Avian lineage H4N6 influenza viruses previously isolated from pigs differ at hemagglutinin amino acids 226 and 228 from H4 subtype viruses isolated from birds. Using a parental H4N6 swine isolate and hemagglutinin mutant viruses (at residues 226 and/or 228), we determined that viruses which contain L226 had a higher affinity for sialic acid alpha2,6 galactose (SAalpha2,6Gal) and a higher infectivity level for primary swine and human respiratory epithelial cells, whereas viruses which contain Q226 had lower SAalpha2,6Gal affinity and lower infectivity levels for both types of cells. Using specific neuraminidases, we found that irrespective of their relative binding preferences, all of the influenza viruses examined utilized SAalpha2,6Gal to infect swine and human cells.
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Allen C
AC
Bateman
Marc G
MG
Busch
Alexander I
AI
Karasin
Nicolai
N
Bovin
Christopher W
CW
Olsen
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry; D006388:Hemagglutinins / Q000737:chemistry; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D007251:Influenza, Human / Q000821:virology; D007700:Kinetics; D009154:Mutation; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D012794:Sialic Acids / Q000378:metabolism*; D013552:Swine; D014132:Trachea / Q000166:cytology* / Q000821:virology
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006388:Hemagglutinins; D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid