A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence

• DOI: 10.1371/journal.ppat.0030141
• Publication Date: 2007-09-28T12:15:39Z
• Authors: Gina M Conenello; Dmitriy Zamarin; Lucy A Perrone; Terrence Tumpey; Peter Palese
• Keywords: Pathogenesis; Recombinant virus; Reverse Genetics

The proapoptotic PB1-F2 protein of influenza A viruses has been shown to contribute pathogenesis in the mouse model. Expression full-length increases virus, causing weight loss, slower viral clearance, and increased titers lungs. After comparing from Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found sequence at position 66 that correlated with pathogenicity. This same also 1918 pandemic A/Brevig Mission/18 virus. Two isogenic recombinant chimeric were created an A/WSN/33 virus background containing PB1 segment HK/156/97: WH N66S. In mice infected N66S there pathogenicity as measured by loss decreased survival, a 100-fold increase replication when compared strain reconstructed pathogenicity-reducing mutation (S66N). resultant S66N attenuated having 3-log lower 50% lethal dose caused less morbidity mortality than wild-type Viral lung S66N-infected virus-infected mice. addition, both S (WH wt 1918) induced elevated levels cytokines lungs Together, these data show single substitution can result could be factors contributing high lethality seen