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Article: Higher polymerase activity of a human influenza virus enhances activation of the hemagglutinin-induced Raf/MEK/ERK signal cascade

TitleHigher polymerase activity of a human influenza virus enhances activation of the hemagglutinin-induced Raf/MEK/ERK signal cascade
Authors
Issue Date2007
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.virologyj.com/home/
Citation
Virology Journal, 2007, v. 4 How to Cite?
AbstractInfluenza viruses replicate within the nucleus of infected cells. Viral genomic RNA, three polymerase subunits (PB2, PB1, and PA), and the nucleoprotein (NP) form ribonucleoprotein complexes (RNPs) that are exported from the nucleus late during the infectious cycle. The virus-induced Raf/MEK/ERK (MAPK) signal cascade is crucial for efficient virus replication. Blockade of this pathway retards RNP export and reduces virus titers. Hemagglutinin (HA) accumulation and its tight association with lipid rafts activate ERK and enhance localization of cytoplasmic RNPs. We studied the induction of MAPK signal cascade by two seasonal human influenza A viruses A/HK/218449/06 (H3N2) and A/HK/218847/06 (H1N1) that differed substantially in their replication efficiency in tissue culture. Infection with H3N2 virus, which replicates efficiently, resulted in higher HA expression and its accumulation on the cell membrane, leading to substantially increased activation of MAPK signaling compared to that caused by H1N1 subtype. More H3N2-HAs were expressed and accumulated on the cell membrane than did H1N1-HAs. Viral polymerase genes, particularly H3N2-PB1 and H3N2-PB2, were observed to contribute to increased viral polymerase activity. Applying plasmid-based reverse genetics to analyze the role of PB1 protein in activating HA-induced MAPK cascade showed that recombinant H1N1 virus possessing the H3N2-PB1 (rgH1N1/H3N2-PB1) induced greater ERK activation, resulting in increased nuclear export of the viral genome and higr virus titers. We conclude that enhanced viral polymerase activity promotes the replication and transcription of viral RNA leading to increased accumulation of HA on the cell surface and thereby resulting in an upregulation of the MAPK cascade and more efficient nuclear RNP-export as well as virus production. © 2007 Marjuki et al; licensee BioMed Central Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/179807
ISSN
2015 Impact Factor: 2.362
2015 SCImago Journal Rankings: 1.166
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMarjuki, Hen_US
dc.contributor.authorYen, HLen_US
dc.contributor.authorFranks, Jen_US
dc.contributor.authorWebster, RGen_US
dc.contributor.authorPleschka, Sen_US
dc.contributor.authorHoffmann, Een_US
dc.date.accessioned2012-12-19T10:05:00Z-
dc.date.available2012-12-19T10:05:00Z-
dc.date.issued2007en_US
dc.identifier.citationVirology Journal, 2007, v. 4en_US
dc.identifier.issn1743-422Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/179807-
dc.description.abstractInfluenza viruses replicate within the nucleus of infected cells. Viral genomic RNA, three polymerase subunits (PB2, PB1, and PA), and the nucleoprotein (NP) form ribonucleoprotein complexes (RNPs) that are exported from the nucleus late during the infectious cycle. The virus-induced Raf/MEK/ERK (MAPK) signal cascade is crucial for efficient virus replication. Blockade of this pathway retards RNP export and reduces virus titers. Hemagglutinin (HA) accumulation and its tight association with lipid rafts activate ERK and enhance localization of cytoplasmic RNPs. We studied the induction of MAPK signal cascade by two seasonal human influenza A viruses A/HK/218449/06 (H3N2) and A/HK/218847/06 (H1N1) that differed substantially in their replication efficiency in tissue culture. Infection with H3N2 virus, which replicates efficiently, resulted in higher HA expression and its accumulation on the cell membrane, leading to substantially increased activation of MAPK signaling compared to that caused by H1N1 subtype. More H3N2-HAs were expressed and accumulated on the cell membrane than did H1N1-HAs. Viral polymerase genes, particularly H3N2-PB1 and H3N2-PB2, were observed to contribute to increased viral polymerase activity. Applying plasmid-based reverse genetics to analyze the role of PB1 protein in activating HA-induced MAPK cascade showed that recombinant H1N1 virus possessing the H3N2-PB1 (rgH1N1/H3N2-PB1) induced greater ERK activation, resulting in increased nuclear export of the viral genome and higr virus titers. We conclude that enhanced viral polymerase activity promotes the replication and transcription of viral RNA leading to increased accumulation of HA on the cell surface and thereby resulting in an upregulation of the MAPK cascade and more efficient nuclear RNP-export as well as virus production. © 2007 Marjuki et al; licensee BioMed Central Ltd.en_US
dc.languageengen_US
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.virologyj.com/home/en_US
dc.relation.ispartofVirology Journalen_US
dc.subject.meshAnimalsen_US
dc.subject.meshDogsen_US
dc.subject.meshEnzyme Activationen_US
dc.subject.meshExtracellular Signal-Regulated Map Kinases - Metabolismen_US
dc.subject.meshHemagglutinins - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshInfluenza A Virus, H1n1 Subtype - Enzymology - Metabolism - Physiologyen_US
dc.subject.meshInfluenza A Virus, H3n2 Subtype - Enzymology - Metabolism - Physiologyen_US
dc.subject.meshInfluenza, Human - Enzymology - Virologyen_US
dc.subject.meshMap Kinase Kinase Kinases - Metabolismen_US
dc.subject.meshMap Kinase Signaling System - Physiologyen_US
dc.subject.meshRna Replicase - Metabolismen_US
dc.subject.meshRibonucleoproteins - Metabolismen_US
dc.subject.meshViral Proteins - Metabolismen_US
dc.subject.meshVirus Replicationen_US
dc.subject.meshRaf Kinases - Metabolismen_US
dc.titleHigher polymerase activity of a human influenza virus enhances activation of the hemagglutinin-induced Raf/MEK/ERK signal cascadeen_US
dc.typeArticleen_US
dc.identifier.emailYen, HL: hyen@hku.hken_US
dc.identifier.authorityYen, HL=rp00304en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1186/1743-422X-4-134en_US
dc.identifier.pmid18053252-
dc.identifier.scopuseid_2-s2.0-38849122079en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-38849122079&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume4en_US
dc.identifier.isiWOS:000252992600002-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridMarjuki, H=14018263900en_US
dc.identifier.scopusauthoridYen, HL=7102476668en_US
dc.identifier.scopusauthoridFranks, J=12786180500en_US
dc.identifier.scopusauthoridWebster, RG=36048363100en_US
dc.identifier.scopusauthoridPleschka, S=6602999462en_US
dc.identifier.scopusauthoridHoffmann, E=7201369718en_US
dc.identifier.citeulike2069573-

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