tetano
Editor, Senior Moderator
Biochim Biophys Acta. 2011 Nov 30. [Epub ahead of print]
Two mutations in the C-terminal domain of influenza virus RNA polymerase PB2 enhance transcription by enhancing cap-1 RNA binding activity.
Zhang S, Wang Q, Wang J, Mizumoto K, Toyoda T.
Source
Unit of Viral Genome Regulation, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 411 Hefei Road, 200025 Shanghai, PR China; Shanghai Medical College of Fudan University, Yixueyuan Road 138, Shanghai 200032, China; Roche R&D Center China LTD, 720 Cai Lun Road, Building 5, Pudong, Shanghai 201203, PR China.
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.
Copyright ? 2011. Published by Elsevier B.V.
PMID:
22146492
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22146492
Two mutations in the C-terminal domain of influenza virus RNA polymerase PB2 enhance transcription by enhancing cap-1 RNA binding activity.
Zhang S, Wang Q, Wang J, Mizumoto K, Toyoda T.
Source
Unit of Viral Genome Regulation, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 411 Hefei Road, 200025 Shanghai, PR China; Shanghai Medical College of Fudan University, Yixueyuan Road 138, Shanghai 200032, China; Roche R&D Center China LTD, 720 Cai Lun Road, Building 5, Pudong, Shanghai 201203, PR China.
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.
Copyright ? 2011. Published by Elsevier B.V.
PMID:
22146492
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22146492