Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus

• DOI: 10.1073/pnas.0711815105
• Publication Date: 2008-02-20T04:33:56Z
• Authors: Claudia Pappas; Patricia V. Aguilar; Christopher F. Ba...; Alicia Solórzano; Hui Zeng; Lucy A. Perrone; Peter Palese; Adolfo García-Sastre; Jacqueline M. Katz; Terrence M. Tumpey
• Keywords: H5N1 genetic structure; Recombinant virus

The 1918 influenza pandemic was exceptionally severe, resulting in the death of up to 50 million people worldwide. Here, we show which virus genes contributed replication and virulence virus. Recombinant viruses, were replaced with from a contemporary human H1N1 virus, A/Texas/36/91 (Tx/91), generated. exchange most seasonal did not alter virus; however, substitution hemagglutinin (HA), neuraminidase (NA), or polymerase subunit PB1 significantly affected ability this cause severe disease mice. observed mice correlated recombinant viruses replicate efficiently airway cells. In second series experiments, eight 1:7 recombinants generated, each Tx/91 gene individually by corresponding Replication capacity individual reassortant assessed mouse lungs Increased titers among containing HA, NA, genes. addition, PB1:Tx/91 (1:7) showed distinctly larger plaque size phenotype than small PA:Tx/91 PB2:Tx/91 reassortants. These results highlight importance for optimal strain.