title: Influenza H1N1 A/Solomon Island/3/06 virus receptor binding specificity correlates with virus pathogenicity, antigenicity, and immunogenicity in ferrets.
abstract: Influenza viruses attach to cells via a sialic acid moiety (sialic acid receptor) that is alpha2-3 linked or alpha2-6 linked to galactose (alpha2-3SAL or alpha2-6SAL); sialic acid acts as a receptor for the virus. Using lectin staining, we demonstrated that the alpha2-6SAL configuration is predominant in the respiratory tract of ferrets, including trachea, bronchus, and lung alveolus tissues. Recombinant wild-type (rWT) influenza A/Solomon Island/3/06 (SI06) (H1N1) viruses were constructed to assess the impact of the hemagglutinin (HA) variations (amino acids 190 or 226) identified in natural variants on virus replication in the upper and lower respiratory tract of ferrets, as well as virus antigenicity and immunogenicity. A single amino acid change at residue 226 (from Gln to Arg) in the HA of SI06 resulted in the complete loss of binding to alpha2-6SAL and a concomitant loss of the virus's ability to replicate in the lower respiratory tract of ferrets. In contrast, the virus with Gln226 in the HA protein has a receptor binding preference for alpha2-6SAL and replicates efficiently in the lungs. There was a good correlation between viral replication in the lungs of ferrets and disease symptoms. In addition, we also showed that the 190 and 226 residues affected viral antigenicity and immunogenicity. Our data emphasize the necessity of thoroughly assessing wild-type influenza viruses for their suitability as reference strains and for carefully selecting the HA antigen for vaccine production during annual influenza vaccine evaluation processes.
authors.affiliation: MedImmune, 319 North Bernardo Ave., Mountain View, CA 94043, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.forename: Weijia
authors.initials: W
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Cheng
authors.forename: James
authors.initials: J
authors.lastname: Zengel
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001980:Bronchi / Q000737:chemistry; D005260:Female; D005289:Ferrets; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology*; D008297:Male; D009976:Orthomyxoviridae Infections / Q000821:virology*; D011650:Pulmonary Alveoli / Q000737:chemistry; D011991:Receptors, Virus / Q000032:analysis*; D012794:Sialic Acids / Q000032:analysis*; D014132:Trachea / Q000737:chemistry; D056189:Viral Tropism; D053585:Virus Attachment
chemical_list: D006389:Hemagglutinins, Viral; D011991:Receptors, Virus; D012794:Sialic Acids; C458881:hemagglutinin fusogenic peptide, influenza virus