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Two mutations in the C-terminal domain of influenza virus RNA polymerase PB2 enhance transcription by enhancing cap-1 RNA binding activity.

Abstract : Influenza virus RNA polymerase (RdRp) PB2 is the cap-1 binding subunit and determines host range and pathogenicity. The mutant human influenza virus RdRp containing PB2 D701N and D701N/S714R demonstrated enhanced replicon activity in mammalian cells. We investigated the influence of these mutations on RdRp activity. Cap-1-dependent transcription activities of D701N/S714R, D701N, and S714R were 348.1±6.2%, 146.4±11%, and 250.1±0.8% of that of the wild type (wt), respectively. Replication activity of these mutants for complimentary RNA to viral RNA ranged from 44% to 53% of that of the wt. Cap-1 RNA-binding activities of D701N/S714R, D701N, and S714R were 262±25%, 257±34%, and 315±9.6% of that of the wt, respectively, and their cap-dependent endonuclease activities were similar to that of the wt. These mutations did not affect template RNA-binding activities. D701N and S714R mutations enhanced transcription by enhancing cap-1 RNA-binding activity, but they may exhibit decreased efficiency of priming by the cap-1 primer. These mutations at the C-terminal domain of PB2 may affect its cap-binding domain.
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https://hal-riip.archives-ouvertes.fr/pasteur-00723715
Contributor : Xiaojing Lin <>
Submitted on : Monday, August 13, 2012 - 11:06:43 AM
Last modification on : Monday, October 8, 2018 - 5:44:04 PM

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Shijian Zhang, Qiang Wang, Jinlan Wang, Kiyohisa Mizumoto, Tetsuya Toyoda. Two mutations in the C-terminal domain of influenza virus RNA polymerase PB2 enhance transcription by enhancing cap-1 RNA binding activity.. BBA - Biochimica et Biophysica Acta, Elsevier, 2012, 1819 (1), pp.78-83. ⟨10.1016/j.bbagrm.2011.11.006⟩. ⟨pasteur-00723715⟩

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