title: Avian-derived NS gene segments alter pathogenicity of the A/Puerto Rico/8/34 virus.
abstract: While the effect of the influenza A virus non-structural protein (NS) on cytokine production during viral infection is well known, inconsistent results have been observed with some other influenza A virus backbone studied. In this study, in order to focus on the impact of the avian NS gene segments on viral virulence, the NS genes encoded by different strains of avian influenza A viruses were incorporated into an identical [A/Puerto Rico/8/1934(H1N1), PR8] virus background to generate various NS recombinant viruses. Thus, PR8NS, PR8×[A/Hong Kong/483/97(H5N1) 483NS, PR8×[A/Ck/Korea/150/03(H9N2) 150NS, and PR8×[A/EM/Korea/W149/06(H5N1) W149NS were constructed utilizing reverse genetics. Here, we show the effects of each of these recombinant viruses upon viral pathogenesis and cytokine production during viral replication in vivo. In this regard, we found that infection of mice with the PR8×150NS recombinant virus resulted in the lowest pathogenicity (6.0×10(4)MLD50), yet elicited the highest levels of TNF-α production in bronchoalveolar lavage (BAL) fluid compared to infection with the other recombinant influenza viruses. In contrast, infection with the PR8 virus showed the highest pathogenicity (1.0×10(2)MLD50) as well as relatively high cytokine levels (IL-1α, IL-1β, IL-17, and eotaxin) in mouse BAL fluid. In addition, the PR8 and PR8×483NS viruses induced severe and extensive inflammation in infected lungs compared with that of PR8×150 NS recombinant virus-infected mice. These results clearly demonstrate that the NS genes of diverse influenza A strains can variable impact pathogenicity, histopathology, and cytokine production in mice even when expressed in an identical genetic background.
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Henugduk-Ku, Cheongju 361-763, 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, 12 Gaeshin-Dong Henugduk-Ku, Cheongju 361-763, Republic of Korea.
authors.forename: Eun Ho
authors.initials: EH
authors.lastname: Lee
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Henugduk-Ku, Cheongju 361-763, Republic of Korea.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Choi
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Henugduk-Ku, Cheongju 361-763, Republic of Korea.
authors.forename: Philippe Noriel Q
authors.initials: PN
authors.lastname: Pascua
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Henugduk-Ku, Cheongju 361-763, Republic of Korea.
authors.forename: Hyeok-Il
authors.initials: HI
authors.lastname: Kwon
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Henugduk-Ku, Cheongju 361-763, Republic of Korea.
authors.forename: Eun-Ha
authors.initials: EH
authors.lastname: Kim
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Henugduk-Ku, Cheongju 361-763, Republic of Korea.
authors.forename: Gyo-Jin
authors.initials: GJ
authors.lastname: Lim
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Henugduk-Ku, Cheongju 361-763, Republic of Korea.
authors.forename: Arun
authors.initials: A
authors.lastname: Decano
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Henugduk-Ku, Cheongju 361-763, Republic of Korea.
authors.forename: Se Mi
authors.initials: SM
authors.lastname: Kim
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Henugduk-Ku, Cheongju 361-763, Republic of Korea. Electronic address: choiki55@chungbuk.ac.kr.
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Choi
mesh_terms: D000818:Animals; D001717:Birds; D002645:Chickens; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000276:immunology / Q000821:virology*; D051379:Mice; D011995:Recombination, Genetic; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: C108309:NS protein, influenza virus; D017361:Viral Nonstructural Proteins
keywords: Cytokine modulation; Influenza A virus; NS protein; Recombinant virus