title: Optimal attenuation of a PR8-derived mouse pathogenic H5N1 recombinant virus for testing antigenicity and protective efficacy in mice.
abstract: The PR8-based reverse genetics vector system is widely used to generate commercial vaccine strains, but the pathogenicity of PR8-derived recombinant viruses in mice hinders further immunological studies. In the present study, we generated PR8-derived H5N1 recombinant viruses, in which haemagglutinin (HA) and neuraminidase (NA) originated from a mouse-pathogenic H5N1 low pathogenic avian influenza virus (LPAIV), and the non-structural proteins (NS) and polymerase basic protein 2 (PB2) originated from different H9N2 LPAIVs. In contrast to the control H5N1 recombinant virus, harboring six internal genes from PR8, the NS and PB2 recombinant viruses did not cause body weight loss in mice. However, the NS recombinant virus replicated in the lungs of mice. It was more immunogenic than the PB2 recombinant virus to protect efficiently against a lethal challenge of a H5N1 highly pathogenic AIV with 89 and 88% amino acid identity in HA and NA, respectively. Therefore, the NS gene may be useful for generating nonpathogenic and immunogenic PR8-derived recombinant viruses for studies of antigenicity and protective efficacy in mice.
authors.affiliation: Laboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Il-Hwan
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Laboratory of Poultry Clinical Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea; Farm Animal Clinical Training and Research Center, Institutes of Green Bio Science and Technology, Seoul National University, Seoul, Republic of Korea; Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. Electronic address: kwonhj01@snu.ac.kr.
authors.forename: Hyuk-Joon
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Laboratory of Avian Diseases, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Jae-Keun
authors.initials: JK
authors.lastname: Park
authors.affiliation: Laboratory of Avian Diseases, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Chang-Seon
authors.initials: CS
authors.lastname: Song
authors.affiliation: Laboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea; Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D008168:Lung / Q000821:virology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology*; D011995:Recombination, Genetic; D059386:Reverse Genetics / Q000379:methods; D016019:Survival Analysis; D014774:Virulence
chemical_list: D000956:Antigens, Viral
keywords: Antigenicity; H5N1; PR8-derived recombinant virus; Pathogenicity; Protective efficacy