title: Effects of different NS genes of avian influenza viruses and amino acid changes on pathogenicity of recombinant A/Puerto Rico/8/34 viruses.
abstract: To examine the effects of the NS1 and NEP genes of avian influenza viruses (AIVs) on pathogenicity in mice, we generated recombinant PR8 viruses containing 3 different NS genes of AIVs. In contrast to the reverse genetics-generated PR8 (rPR8) strain and other recombinant viruses, the recombinant virus rPR8-NS(0028), which contained the NS gene of A/chicken/KBNP-0028/2000 (H9N2) (0028), was non-pathogenic to mice. The novel single mutations of 0028 NS1 to corresponding amino acid of PR8 NS1, G139D and S151T increased the pathogenicity of rPR8-NS(0028). The replacement of the PL motifs (EPEV or RSEV) of pathogenic recombinant viruses with that of 0028 (GSEV) did not reduce the pathogenicity of the viruses. However, a recombinant virus with an EPEV-grafted 0028 NS gene was more pathogenic than rPR8-NS(0028) but less than rPR8. The lower pathogenicity of rPR8-NS(0028) might be associated with the lower virus titer and IFN-β level in the lungs of infected mice, and be attributed to G139, S151 and GSEV-PL motif of NS1 gene of 0028. In conclusion we defined new amino acid residues of NS1 related to mice pathogenicity and the presence of pathogenic NS genes among low pathogenic AIVs may encourage continuous monitoring of their mammalian pathogenicity.
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: Il-Hwan
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea; Laboratory of Poultry Clinical Science, College of Veterinary Medicine, Seoul National University, Pyeongchang, Gangwon-do, Republic of Korea. Electronic address: kwonhj01@snu.ac.kr.
authors.forename: Hyuk-Joon
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Su-Hyung
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea; Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Kim
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. Electronic address: kimhong@snu.ac.kr.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens / Q000821:virology*; D005260:Female; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics* / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000276:immunology / Q000821:virology*; D016899:Interferon-beta / Q000378:metabolism; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014774:Virulence
chemical_list: D017361:Viral Nonstructural Proteins; D016899:Interferon-beta
keywords: Avian influenza virus; NS gene; PL motif; Pathogenicity; Reverse genetics