title: Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models.
abstract: In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model.
authors.affiliation: Novosibirsk State University, 630090 Novosibirsk, Russian Federation; Federal State Budgetary Scientific Institution "Research Institute of Experimental and Clinical Medicine", Siberian Branch of the Russian Academy of Medical Sciences, 630117 Novosibirsk, Russian Federation. Electronic address: ellap@bk.ru.
authors.forename: E A
authors.initials: EA
authors.lastname: Prokopyeva
authors.affiliation: Federal State Budgetary Scientific Institution "Research Institute of Experimental and Clinical Medicine", Siberian Branch of the Russian Academy of Medical Sciences, 630117 Novosibirsk, Russian Federation.
authors.forename: I A
authors.initials: IA
authors.lastname: Sobolev
authors.affiliation: Novosibirsk State University, 630090 Novosibirsk, Russian Federation.
authors.forename: M V
authors.initials: MV
authors.lastname: Prokopyev
authors.affiliation: Federal State Budgetary Scientific Institution "Research Institute of Experimental and Clinical Medicine", Siberian Branch of the Russian Academy of Medical Sciences, 630117 Novosibirsk, Russian Federation.
authors.forename: A M
authors.initials: AM
authors.lastname: Shestopalov
mesh_terms: D000220:Adaptation, Biological; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D004195:Disease Models, Animal; D016679:Genome, Viral; D059014:High-Throughput Nucleotide Sequencing; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000821:virology*; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D014764:Viral Proteins
keywords: BALB/c; C57BL/6z and CD1 mice; Influenza А(H1N1)pdm09 virus adaptation; Interstitial pneumonia; Lungs; Nonstructural protein PB1-F2; Protein mutation