Binding of the hemagglutinin from human or equine influenza H3 viruses to the receptor is altered by substitutions at residue 193

• Published in: Archives of virology Vol. 149; no. 8; pp. 1663 - 1671
• Main Authors: Medeiros, R, Naffakh, N, Manuguerra, J.C, Werf, S. van der
• Format: Journal Article
• Language: English
• Published: Wien Springer 01-08-2004; New York, NY Springer Nature B.V
• Subjects: Amino Acid Substitution; Animals; Biological and medical sciences; Cercopithecus aethiops; Chickens; COS Cells; erythrocytes; Erythrocytes - metabolism; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Hemagglutination, Viral; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; Horses; host specificity; Human viral diseases; Humans; Infectious diseases; Influenza A virus; Medical sciences; Microbiology; Miscellaneous; Mutation; N-Acetylneuraminic Acid; Receptors, Virus - metabolism; Sheep; sialic acids; Viral diseases; Virology; Infection; Human; Vertebrata; H3 histamine receptor; Mammalia; Hemagglutinin; Viral disease; Horse; Perissodactyla; Veterinary; Equine influenza; Ungulata
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s00705-003-0287-2

Interactions of the hemagglutinin (HA) of influenza viruses with sialic acids (SA) are important for host range restriction. Most human H3s have a Ser193, while avian and equine H3s usually have an Asn or a Lys, respectively. To investigate the role of residue 193 in the recognition of SA, substitutions were introduced by mutagenesis within a human H3 and an equine H3. Hemadsorption assays performed on COS-1 cells expressing wt or mutated HAs, showed that a K193S substitution in the context of an equine H3 decreased its ability to bind several animal erythrocytes. Using de- and then alpha2,3 or alpha2,6 re-sialylated chicken erythrocytes we showed that for both human and equine H3s, substitution of a Serine by positively-charged Arginine or Lysine at position 193 increased binding to its preferred receptor, SAalpha2,6Gal and SAalpha2,3Gal, respectively. Moreover, when combined with the L194I substitution, the S193R substitution induced binding of the human H3 to NeuAcalpha2,3Gal.