title: Rapid acquisition of polymorphic virulence markers during adaptation of highly pathogenic avian influenza H5N8 virus in the mouse.
abstract: Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health. Although the H5N8 virus has been only moderately pathogenic to mammalian hosts, virulence can still increase. We evaluated the pathogenic potential of several H5N8 strains via the mouse-adaptation method. Two H5N8 viruses were sequentially passaged in BALB/c mice and plaque-purified from lung samples. The viruses rapidly obtained high virulence (MLD50, up to 0.5 log10 PFU/mL) within 5 passages. Sequence analysis revealed the acquisition of several virulence markers, including the novel marker P708S in PB1 gene. Combinations of markers synergistically enhanced viral replication and polymerase activity in human cell lines and virulence and multiorgan dissemination in mice. These results suggest that H5N8 viruses can rapidly acquire virulence markers in mammalian hosts; thus, rapid spread as well as repeated viral introduction into the hosts may significantly increase the risk of human infection and elevate pandemic potential.
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Won-Suk
authors.initials: WS
authors.lastname: Choi
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Baek
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Jin Jung
authors.initials: JJ
authors.lastname: Kwon
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Ju Hwan
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea.
authors.forename: Sun-Woo
authors.initials: SW
authors.lastname: Yoon
authors.affiliation: Microbiomics and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea.
authors.forename: Jungwon
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Microbiomics and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Dae Jeon 305-764, Republic of Korea.
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Choi
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Min-Suk
authors.initials: MS
authors.lastname: Song
mesh_terms: D000220:Adaptation, Biological; D056809:Alveolar Epithelial Cells / Q000821:virology; D019943:Amino Acid Substitution; D000818:Animals; D005814:Genes, Viral; D016679:Genome, Viral; D000071225:Influenza A Virus, H5N8 Subtype / Q000472:pathogenicity / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000821:virology*; D010641:Phenotype; D014774:Virulence; D014779:Virus Replication