title: In vitro and in vivo replication of influenza A H1N1 WSN33 viruses with different M1 proteins.
abstract: The M1 protein is a major structural protein that has multiple functions in various steps within the life cycle of the influenza A virus (IAV). However, little is currently known about the role of M1 in IAV replication in vivo and the associated pathogenesis. In this study, six isogenic H1N1 WSN33 viruses, constructed to express unique M1 proteins derived from various strains, subtypes or WSN33 itself, were tested to determine in vitro and in vivo functional exchangeability of M1 proteins in the replication and pathogenesis of the WSN33 virus. Despite five chimeric M1 viruses replicating to levels similar to those of the parental WSN33 virus in cell cultures, all M1 chimeras exhibited improved replication and enhanced virulence in mice when compared with the WSN33 virus. Interestingly, M1 proteins derived from swine viruses caused more severe clinical diseases than those from human or quail. These data indicate that the M1 protein is an important determinant of viral replication and pathogenic properties in mice, although the functions of M1 observed in vivo are not adequately reflected in simple infections of cultured cells. Chimeric M1 viruses that are variable in their clinical manifestations described here will aid future understanding of the role of M1 in IAV pathogenesis.
authors.affiliation: Veterinary Diagnostic Division, Chongqing Municipal Center for Animal Disease Control and Prevention, Chongqing 401120, PR China.|Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, USA.|Department of Biology and Microbiology, South Dakota State University, Brookings, SD, USA.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Ran
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Huigang
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, USA.|Department of Biology and Microbiology, South Dakota State University, Brookings, SD, USA.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Xiang
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Qinfang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Bawa
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Wenbao
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, USA.|Department of Biology and Microbiology, South Dakota State University, Brookings, SD, USA.
authors.forename: Laihua
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Young
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Juergen
authors.initials: J
authors.lastname: Richt
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ma
authors.affiliation: Shandong Academy of Agricultural Sciences, Jinan, PR China.|Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, USA.|Department of Biology and Microbiology, South Dakota State University, Brookings, SD, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000821:virology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D016019:Survival Analysis; D013552:Swine; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: C488936:M1 protein, Influenza A virus; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; D037521:Virulence Factors