title: Altered pathogenicity for seasonal influenza virus by single reassortment of the RNP genes derived from the 2009 pandemic influenza virus.
abstract: BACKGROUND
  The 2009 influenza A pandemic virus (H1N1(pdm)) may reassort with old seasonal influenza A virus (H1N1₁₄₁) in humans and potentially change their pathogenicity.
  
  
  RESULTS
  This study focuses on the reassortment of ribonucleoproteins (RNPs) among H1N1(pdm) and seasonal influenza A viruses. A single RNP gene reassortment altered reporter gene expression levels driven by polymerase complex in transfection system. The growth rates of recombinant viruses with different RNP recombinations were changed in A549 cells. Mice were infected with recombinant viruses containing single RNP gene reassortment, and pathogenicity was examined. The results demonstrated that the median lethal dose (LD₅₀) of the PB2₁₄₁/PB1₁₄₁/PA(pdm)/NP₁₄₁ recombinant virus was lower than that of the seasonal H1N1 virus. Viral titers of this reassorted virus in the lung and spleen were significantly higher than that in seasonal H1N1 virus-challenged mice.
  
  
  CONCLUSIONS
  Although the changes of RNP activity did not exactly reflect to mice virulence, we consistently observed that the PA gene of H1N1(pdm) results in increased polymerase activity, better replication in mice, and lower LD₅₀. Our findings suggest that monitoring of gene reassortment for the 2009 pandemic influenza and seasonal human viruses is also important, which would help to constrain the potential emergence of a more virulent influenza A variant.
authors.affiliation: Research Center for Emerging Viral Infections, Chang Gung University, TaoYuan, Taiwan.
authors.forename: Erh-Fang
authors.initials: EF
authors.lastname: Hsieh
authors.forename: Sue-Jane
authors.initials: SJ
authors.lastname: Lin
authors.forename: Chee-Keng
authors.initials: CK
authors.lastname: Mok
authors.forename: Guang-Wu
authors.initials: GW
authors.lastname: Chen
authors.forename: Chih-Heng
authors.initials: CH
authors.lastname: Huang
authors.forename: Yeau-Ching
authors.initials: YC
authors.lastname: Wang
authors.forename: Tzu-Chun
authors.initials: TC
authors.lastname: Chen
authors.forename: Chi-Jene
authors.initials: CJ
authors.lastname: Chen
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000473:pathology* / Q000821:virology*; D016601:RNA-Binding Proteins / Q000235:genetics*; D016865:Reassortant Viruses / Q000235:genetics / Q000472:pathogenicity*; D012376:Rodent Diseases / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D014758:Viral Core Proteins / Q000235:genetics*; D014774:Virulence
chemical_list: C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins