Altered pathogenicity for seasonal influenza virus by single reassortment of the RNP genes derived from the 2009 pandemic influenza virus

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. Methods and 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 PB2 ₁₄₁/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 viruschallenged 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.