Sialic acid recognition is a key determinant of influenza A virus tropism in murine trachea epithelial cell cultures.
Influenza A virus interacts with specific types of sialic acid during attachment and entry into susceptible cells. The precise amino acids in the hemagglutinin protein that control sialic acid binding specificity and affinity vary among antigenic subtypes. For H3 subtypes, amino acids 226 and 228 are critical for differentiating between alpha2,3- and alpha2,6-linked forms of sialic acid (SA). We demonstrate that position 190 of the HA from A/Udorn/307/72 (H3N2) plays an important role in the recognition of alpha2,3-SA, as changing the residue from a glutamic acid to an aspartic acid led to alteration of red blood cell hemagglutination and a complete loss of replication in differentiated, murine trachea epithelial cell cultures which express only alpha2,3-SA. This amino acid change had a minimal effect on virus replication in MDCK cells, suggesting subtle changes in receptor recognition by the H3 hemagglutinin can lead to significant alterations in cell and species tropism.
Pekosz
Andrew
A
Dept. of Molecular Microbiology, Washington University in St. Louis School of Medicine, 660 South Euclid Avenue, Campus Box 8230, St. Louis, MO 63110, USA. apekosz@jhsph.edu
Newby
Celeste
C
Bose
Pulkit S
PS
Lutz
Andrew
A
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000821:virology*; D018698:Glutamic Acid / Q000235:genetics; D006384:Hemagglutination; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000378:metabolism; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020125:Mutation, Missense; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D014132:Trachea / Q000821:virology; D010948:Viral Plaque Assay; D053585:Virus Attachment; D014779:Virus Replication
D006389:Hemagglutinins, Viral; C458881:hemagglutinin fusogenic peptide, influenza virus; D018698:Glutamic Acid; D019158:N-Acetylneuraminic Acid