Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein
dc.contributor.author | Boergeling, Yvonne | |
dc.contributor.author | Rozhdestvensky, Timofey S. | |
dc.contributor.author | Schmolke, Mirco | |
dc.contributor.author | Resa-Infante, Patricia | |
dc.contributor.author | Robeck, Thomas | |
dc.contributor.author | Randau, Gerrit | |
dc.contributor.author | Wolff, Thorsten | |
dc.contributor.author | Gabriel, Gülsah | |
dc.contributor.author | Brosius, Jürgen | |
dc.contributor.author | Ludwig, Stephan | |
dc.date.accessioned | 2018-05-07T18:16:25Z | |
dc.date.available | 2018-05-07T18:16:25Z | |
dc.date.created | 2015-06-09 | |
dc.date.issued | 2015-05-29 | none |
dc.identifier.other | http://edoc.rki.de/oa/articles/reRnT0Z2w5k/PDF/220LBuUYlHPYY.pdf | |
dc.identifier.uri | http://edoc.rki.de/176904/2071 | |
dc.description.abstract | Influenza A virus (IAV) defective RNAs are generated as byproducts of error-prone viral RNA replication. They are commonly derived from the larger segments of the viral genome and harbor deletions of various sizes resulting in the generation of replication incompatible viral particles. Furthermore, small subgenomic RNAs are known to be strong inducers of pattern recognition receptor RIG-I-dependent type I interferon (IFN) responses. The present study identifies a novel IAV-induced defective RNA derived from the PB2 segment of A/Thailand/1(KAN-1)/2004 (H5N1). It encodes a 10 kDa protein (PB2∆) sharing the N-terminal amino acid sequence of the parental PB2 protein followed by frame shift after internal deletion. PB2∆ induces the expression of IFNβ and IFN-stimulated genes by direct interaction with the cellular adapter protein MAVS, thereby reducing viral replication of IFN-sensitive viruses such as IAV or vesicular stomatitis virus. This induction of IFN is completely independent of the defective RNA itself that usually serves as pathogen-associated pattern and thus does not require the cytoplasmic sensor RIG-I. These data suggest that not only defective RNAs, but also some defective RNA-encoded proteins can act immunostimulatory. In this particular case, the KAN-1-induced defective RNA-encoded protein PB2∆ enhances the overwhelming immune response characteristic for highly pathogenic H5N1 viruses, leading to a more severe phenotype in vivo. | eng |
dc.language.iso | eng | |
dc.publisher | Robert Koch-Institut, Infektionskrankheiten / Erreger | |
dc.subject | Animals | eng |
dc.subject | Mice | eng |
dc.subject | Real-Time Polymerase Chain Reaction | eng |
dc.subject | Viral Proteins/genetics | eng |
dc.subject | RNA Viral/genetics | eng |
dc.subject | Viral Proteins/metabolism | eng |
dc.subject | Mice Inbred BALB C | eng |
dc.subject | Virus Replication | eng |
dc.subject | Blotting Western | eng |
dc.subject | Influenza A virus/physiology | eng |
dc.subject | Reverse Transcriptase Polymerase Chain Reaction | eng |
dc.subject | RNA Messenger/genetics | eng |
dc.subject | Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization | eng |
dc.subject | Blotting Northern | eng |
dc.subject | Hemagglutination Tests | eng |
dc.subject | Immunoprecipitation | eng |
dc.subject | Interferon Type I/genetics | eng |
dc.subject | Interferon Type I/metabolism | eng |
dc.subject | Orthomyxoviridae Infections/metabolism | eng |
dc.subject | Orthomyxoviridae Infections/virology | eng |
dc.subject | RNA Replicase/genetics | eng |
dc.subject | RNA Replicase/metabolism | eng |
dc.subject | Tumor Cells Cultured | eng |
dc.subject.ddc | 610 Medizin | |
dc.title | Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein | |
dc.type | periodicalPart | |
dc.identifier.urn | urn:nbn:de:0257-10039618 | |
dc.identifier.doi | 10.1371/journal.ppat.1004924 | |
dc.identifier.doi | http://dx.doi.org/10.25646/1996 | |
local.edoc.container-title | PLoS Pathogens | |
local.edoc.container-text | Boergeling Y, Rozhdestvensky TS, Schmolke M, Resa-Infante P, Robeck T, Randau G, et al. (2015) Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein. PLoS Pathog 11(5): e1004924. | |
local.edoc.fp-subtype | Artikel | |
local.edoc.type-name | Zeitschriftenartikel | |
local.edoc.container-type | periodical | |
local.edoc.container-type-name | Zeitschrift | |
local.edoc.container-url | http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004924 | |
local.edoc.container-publisher-name | Public Library of Science | |
local.edoc.container-volume | 11 | |
local.edoc.container-issue | 5 | |
local.edoc.container-year | 2015 |