title: Adaption of seasonal H1N1 influenza virus in mice.
abstract: The experimental infection of a mouse lung with influenza A virus has proven to be an invaluable model for studying the mechanisms of viral adaptation and virulence. The mouse adaption of human influenza A virus can result in mutations in the HA and other proteins, which is associated with increased virulence in mouse lungs. In this study, a mouse-adapted seasonal H1N1 virus was obtained through serial lung-to-lung passages and had significantly increased virulence and pathogenicity in mice. Genetic analysis indicated that the increased virulence of the mouse-adapted virus was attributed to incremental acquisition of three mutations in the HA protein (T89I, N125T, and D221G). However, the mouse adaption of influenza A virus did not change the specificity and affinity of receptor binding and the pH-dependent membrane fusion of HA, as well as the in vitro replication in MDCK cells. Notably, infection with the mouse adapted virus induced severe lymphopenia and modulated cytokine and chemokine responses in mice. Apparently, mouse adaption of human influenza A virus may change the ability to replicate in mouse lungs, which induces strong immune responses and inflammation in mice. Therefore, our findings may provide new insights into understanding the mechanisms underlying the mouse adaption and pathogenicity of highly virulent influenza viruses.
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Comparative Medicine Center, Peking Union Medical Collage, Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.forename: Linlin
authors.initials: L
authors.lastname: Bao
authors.forename: Fengdi
authors.initials: F
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Lv
authors.forename: Yila
authors.initials: Y
authors.lastname: Ma
authors.forename: Jiangfang
authors.initials: J
authors.lastname: Zhou
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zhan
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Chunmei
authors.initials: C
authors.lastname: Ma
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D018925:Chemokines / Q000276:immunology; D004285:Dogs; D016679:Genome, Viral / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D007700:Kinetics; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D011485:Protein Binding; D012621:Seasons; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D014764:Viral Proteins / Q000737:chemistry; D014779:Virus Replication / Q000502:physiology
chemical_list: D018925:Chemokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014764:Viral Proteins