Identification of the N-terminal domain of the influenza virus PA responsible for the suppression of host protein synthesis.

2.50
Hdl Handle:
http://hdl.handle.net/10033/292559
Title:
Identification of the N-terminal domain of the influenza virus PA responsible for the suppression of host protein synthesis.
Authors:
Desmet, Emily A; Bussey, Kendra A; Stone, Raychel; Takimoto, Toru
Abstract:
Cellular protein synthesis is suppressed during influenza virus infection, allowing for preferential production of viral proteins. To explore the impact of polymerase subunits on protein synthesis, we coexpressed enhanced green fluorescent protein (eGFP) or luciferase together with each polymerase component or NS1 of A/California/04/2009 (Cal) and found that PA has a significant impact on the expression of eGFP and luciferase. Comparison of the suppressive activity on coexpressed proteins between various strains revealed that avian virus or avian-origin PAs have much stronger activity than human-origin PAs, such as the one from A/WSN/33 (WSN). Protein synthesis data suggested that reduced expression of coexpressed proteins is not due to PA's reported proteolytic activity. A recombinant WSN containing Cal PA showed enhanced host protein synthesis shutoff and induction of apoptosis. Further characterization of the PA fragment indicated that the N-terminal domain (PANt), which includes the endonuclease active site, is sufficient to suppress cotransfected gene expression. By characterizing various chimeric PANts, we found that multiple regions of PA, mainly the helix α4 and the flexible loop of amino acids 51 to 74, affect the activity. The suppressive effect of PANt cDNA was mainly due to PA-X, which was expressed by ribosomal frameshifting. In both Cal and WSN viruses, PA-X showed a stronger effect than the corresponding PANt, suggesting that the unique C-terminal sequences of PA-X also play a role in suppressing cotransfected gene expression. Our data indicate strain variations in PA gene products, which play a major role in suppression of host protein synthesis.
Affiliation:
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Citation:
Identification of the N-terminal domain of the influenza virus PA responsible for the suppression of host protein synthesis. 2013, 87 (6):3108-18 J. Virol.
Journal:
Journal of virology
Issue Date:
Mar-2013
URI:
http://hdl.handle.net/10033/292559
DOI:
10.1128/JVI.02826-12
PubMed ID:
23283952
Type:
Article
Language:
en
ISSN:
1098-5514
Appears in Collections:
junior research group immunomodulation (VIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorDesmet, Emily Aen_GB
dc.contributor.authorBussey, Kendra Aen_GB
dc.contributor.authorStone, Raychelen_GB
dc.contributor.authorTakimoto, Toruen_GB
dc.date.accessioned2013-05-21T14:14:21Z-
dc.date.available2013-05-21T14:14:21Z-
dc.date.issued2013-03-
dc.identifier.citationIdentification of the N-terminal domain of the influenza virus PA responsible for the suppression of host protein synthesis. 2013, 87 (6):3108-18 J. Virol.en_GB
dc.identifier.issn1098-5514-
dc.identifier.pmid23283952-
dc.identifier.doi10.1128/JVI.02826-12-
dc.identifier.urihttp://hdl.handle.net/10033/292559-
dc.description.abstractCellular protein synthesis is suppressed during influenza virus infection, allowing for preferential production of viral proteins. To explore the impact of polymerase subunits on protein synthesis, we coexpressed enhanced green fluorescent protein (eGFP) or luciferase together with each polymerase component or NS1 of A/California/04/2009 (Cal) and found that PA has a significant impact on the expression of eGFP and luciferase. Comparison of the suppressive activity on coexpressed proteins between various strains revealed that avian virus or avian-origin PAs have much stronger activity than human-origin PAs, such as the one from A/WSN/33 (WSN). Protein synthesis data suggested that reduced expression of coexpressed proteins is not due to PA's reported proteolytic activity. A recombinant WSN containing Cal PA showed enhanced host protein synthesis shutoff and induction of apoptosis. Further characterization of the PA fragment indicated that the N-terminal domain (PANt), which includes the endonuclease active site, is sufficient to suppress cotransfected gene expression. By characterizing various chimeric PANts, we found that multiple regions of PA, mainly the helix α4 and the flexible loop of amino acids 51 to 74, affect the activity. The suppressive effect of PANt cDNA was mainly due to PA-X, which was expressed by ribosomal frameshifting. In both Cal and WSN viruses, PA-X showed a stronger effect than the corresponding PANt, suggesting that the unique C-terminal sequences of PA-X also play a role in suppressing cotransfected gene expression. Our data indicate strain variations in PA gene products, which play a major role in suppression of host protein synthesis.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Journal of virologyen_GB
dc.subject.meshDNA Mutational Analysisen_GB
dc.subject.meshGenes, Reporteren_GB
dc.subject.meshGreen Fluorescent Proteinsen_GB
dc.subject.meshHost-Pathogen Interactionsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInfluenza A virusen_GB
dc.subject.meshLuciferasesen_GB
dc.subject.meshProtein Biosynthesisen_GB
dc.subject.meshRepressor Proteinsen_GB
dc.subject.meshViral Nonstructural Proteinsen_GB
dc.subject.meshVirulence Factorsen_GB
dc.titleIdentification of the N-terminal domain of the influenza virus PA responsible for the suppression of host protein synthesis.en
dc.typeArticleen
dc.contributor.departmentDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.en_GB
dc.identifier.journalJournal of virologyen_GB

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