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Article: PAN substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities

TitlePAN substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities
Authors
KeywordsInfluenza A virus
PAN-A37S
PAN-A37S/I61T
PAN-A37S/V63I
Polymerase activity
Endonuclease activity
Issue Date2017
PublisherSociety for General Microbiology. The Journal's web site is located at http://vir.sgmjournals.org
Citation
Journal of General Virology, 2017, v. 98 n. 3, p. 364-373 How to Cite?
AbstractSubstitutions in the PA N-terminus (PAN) of influenza A viruses are associated with viral pathogenicity. During our previous study, which identified PAN-V63I and -A37S/I61T/V63I/V100A substitutions as virulence determinants, we observed a severe decrease in virus growth and transcription/replication capacity posed by PAN-A37S/V100A substitution. To further delineate the significance of substitutions at these positions, we generated mutant H7N7 viruses bearing the substitutions PAN-A37S, -A37S/I61T, -A37S/V63I, -V100A, -I61T/V100A and -V63I/V100A by reverse genetics. Our results showed that all mutant viruses except PAN-V100A showed a significantly reduced growth capability in infected cells. At the same time, the PAN-A37S, -A37S/I61T and -A37S/V63I mutant viruses displayed decreased viral transcription and replication by diminishing virus RNA synthesis activity. Biochemical assays indicated that the substitutions PAN-A37S, -A37S/I61T and -A37S/V63I suppressed the polymerase and endonuclease activities when compared with those of the wild-type. Together, our results demonstrated that the PAN-A37S, -A37S/I61T and -A37S/V63I substitutions contributed to a decreased pathogenicity of avian H7N7 influenza A virus.
Persistent Identifierhttp://hdl.handle.net/10722/243182
ISSN
2017 Impact Factor: 2.514
2015 SCImago Journal Rankings: 1.741
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, M-
dc.contributor.authorYuan, S-
dc.contributor.authorYe, Z-
dc.contributor.authorSingh, K-
dc.contributor.authorLi, C-
dc.contributor.authorShuai, H-
dc.contributor.authorNg, F-
dc.contributor.authorChow, BKC-
dc.contributor.authorChu, H-
dc.contributor.authorZheng, B-
dc.date.accessioned2017-08-25T02:51:15Z-
dc.date.available2017-08-25T02:51:15Z-
dc.date.issued2017-
dc.identifier.citationJournal of General Virology, 2017, v. 98 n. 3, p. 364-373-
dc.identifier.issn0022-1317-
dc.identifier.urihttp://hdl.handle.net/10722/243182-
dc.description.abstractSubstitutions in the PA N-terminus (PAN) of influenza A viruses are associated with viral pathogenicity. During our previous study, which identified PAN-V63I and -A37S/I61T/V63I/V100A substitutions as virulence determinants, we observed a severe decrease in virus growth and transcription/replication capacity posed by PAN-A37S/V100A substitution. To further delineate the significance of substitutions at these positions, we generated mutant H7N7 viruses bearing the substitutions PAN-A37S, -A37S/I61T, -A37S/V63I, -V100A, -I61T/V100A and -V63I/V100A by reverse genetics. Our results showed that all mutant viruses except PAN-V100A showed a significantly reduced growth capability in infected cells. At the same time, the PAN-A37S, -A37S/I61T and -A37S/V63I mutant viruses displayed decreased viral transcription and replication by diminishing virus RNA synthesis activity. Biochemical assays indicated that the substitutions PAN-A37S, -A37S/I61T and -A37S/V63I suppressed the polymerase and endonuclease activities when compared with those of the wild-type. Together, our results demonstrated that the PAN-A37S, -A37S/I61T and -A37S/V63I substitutions contributed to a decreased pathogenicity of avian H7N7 influenza A virus.-
dc.languageeng-
dc.publisherSociety for General Microbiology. The Journal's web site is located at http://vir.sgmjournals.org-
dc.relation.ispartofJournal of General Virology-
dc.subjectInfluenza A virus-
dc.subjectPAN-A37S-
dc.subjectPAN-A37S/I61T-
dc.subjectPAN-A37S/V63I-
dc.subjectPolymerase activity-
dc.subjectEndonuclease activity-
dc.titlePAN substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities-
dc.typeArticle-
dc.identifier.emailHu, M: meng16hu@hku.hk-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailYe, Z: zwye@hku.hk-
dc.identifier.emailLi, C: licun@hku.hk-
dc.identifier.emailNg, F: fng@hku.hk-
dc.identifier.emailChow, BKC: bkcc@hku.hk-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailZheng, B: bzheng@hkucc.hku.hk-
dc.identifier.authorityChow, BKC=rp00681-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityZheng, B=rp00353-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1099/jgv.0.000717-
dc.identifier.pmid28113045-
dc.identifier.scopuseid_2-s2.0-85017011014-
dc.identifier.hkuros273769-
dc.identifier.volume98-
dc.identifier.issue3-
dc.identifier.spage364-
dc.identifier.epage373-
dc.identifier.isiWOS:000399235600008-
dc.publisher.placeUnited Kingdom-

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