title: Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants.
abstract: In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential.
authors.affiliation: D.I. Ivanovsky Institute of Virology, 123098 Moscow, Russia.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Rudneva
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Timofeeva
authors.forename: Anna V
authors.initials: AV
authors.lastname: Ignatieva
authors.forename: Aleksandr A
authors.initials: AA
authors.lastname: Shilov
authors.forename: Petr S
authors.initials: PS
authors.lastname: Krylov
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ilyushina
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Kaverin
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002642:Chick Embryo; D002645:Chickens; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D013696:Temperature; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D050505:Mutant Proteins; D012367:RNA, Viral; C109963:hemagglutinin, avian influenza A virus
keywords: H5 hemagglutinin; Influenza escape mutants; Pleiotropic antibody-neutralizing mutations