title: [Effect of Point Mutations in the Polymerase Genes of the Influenza A/PR/8/34 (H1N1) Virus on the Immune Response in a Mouse Model].
abstract: The vaccine strains for live attenuated influenza vaccines (LAIVs) have cold-adapted, temperature-sensitive, and attenuated phenotypes, which are guaranteed by the presence of specific mutations from the master donor virus in their internal genes. In this study, we used mutant viruses of the pathogenic A/Puerto Rico/8/34 (H1N1) that contained ts-mutations in PB1 (K265N, V591I), PB2 (V478L), and PA (L28P, V341L) genes along and/or in different combinations to evaluate the impact of these mutations in the immune responses. Sequential addition of tested mutations resulted in the stepwise decrease in virus-specific serum and, to a lesser extent, mucosal antibody levels. We demonstrated strong positive correlation between virus attenuation (virus titer in lung) and antibody titers. The ts-mutations in PB1, PB2, and PA genes are mostly involved in the modulation of the humoral immunity, but also have a moderate effect on the cellular adaptive immune response.
authors.forename: S A
authors.initials: SA
authors.lastname: Kuznetsova
authors.forename: I N
authors.initials: IN
authors.lastname: Isakova-Sivak
authors.forename: V A
authors.initials: VA
authors.lastname: Kuznetcova
authors.forename: G D
authors.initials: GD
authors.lastname: Petukhova
authors.forename: I V
authors.initials: IV
authors.lastname: Losev
authors.forename: S A
authors.initials: SA
authors.lastname: Donina
authors.forename: L G
authors.initials: LG
authors.lastname: Rudenko
authors.forename: A N
authors.initials: AN
authors.lastname: Naikhin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007111:Immunity, Cellular; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D009976:Orthomyxoviridae Infections; D017354:Point Mutation / Q000276:immunology*; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: C061290:PA protein, influenza viruses; C502893:PB2 protein, influenza virus; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; D012324:RNA-Dependent RNA Polymerase