Journal
VIROLOGY
Volume 468, Issue -, Pages 545-555Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2014.09.008
Keywords
Influenza; Random mutagenesis; PB2; Polymerase; PB2-627
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Funding
- National Institutes of Health (NIAID) [HHSN272201400006C]
- Research Grant Council of Hong Kong [HKU 776611M]
- Seed Fund for Basic Research [201111159066]
- Area of Excellence Scheme of the University Grants Committee [AoE/M-12/06]
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Sequence analyses of influenza PB2 sequences indicate that the 627 position almost exclusively contains either lysine (K) or glutamic acid (E), suggesting a high sequence constraint at this genetic marker. Here, we used a site-directed random mutagenesis method to demonstrate that PB2-627 position has a high sequence plasticity. Recombinant viruses carrying various amino acid residues at this position are viable in cell cultures. These PB2-627 mutants showed various polymerase activities and replication kinetics in mammalian and avian cells as well as pathogenicity in mice. Serially passaging these mutants in MDCK cells generated some compensatory PB2 mutations that can restore polymerase activities of the PB2-627 mutants. Of these, PB2-D309N was identified as a novel one. Besides showing that influenza virus can tolerate a wide range of amino acid residues at the PB2-627 position, this study also demonstrates a potential strategy to identify novel mutations that can enhance viral polymerase. (C) 2014 Elsevier Inc. All rights reserved.
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