Journal article
The Alpha/Beta Interferon Receptor Provides Protection against Influenza Virus Replication but Is Dispensable for Inflammatory Response Signaling
Journal of virology, Vol.84(4), pp.2027-2037
02/2010
Handle:
https://hdl.handle.net/2376/115087
PMCID: PMC2812385
PMID: 19939913
Abstract
The innate immune response provides the first line of defense against foreign pathogens by responding to molecules that are a signature of a pathogenic infection. Certain RNA viruses, such as influenza virus, produce double-stranded RNA as an intermediate during the replication life cycle, which activates pathogen recognition receptors capable of inducing interferon production. By engaging interferon receptors, interferon activates the JAK-STAT pathway and results in the positive feedback of interferon production, amplifying the response to viral infection. To examine how deficiencies in interferon signaling affect the cellular response to infection, we performed influenza virus infections of mouse embryonic fibroblasts lacking the alpha/beta interferon receptor, the gamma interferon receptor, or both. In the absence of the alpha/beta interferon receptor, we observed increased viral replication but decreased activation of PKR, Stat1, and NF-κB; the presence or absence of the gamma interferon receptor did not exhibit discernible differences in these readouts. Analysis of gene expression profiles showed that while cells lacking the alpha/beta interferon receptor exhibited decreased levels of transcription of antiviral genes, genes related to inflammatory and apoptotic responses were transcribed to levels similar to those of cells containing the receptor. These results indicate that while the alpha/beta interferon receptor is needed to curb viral replication, it is dispensable for the induction of certain inflammatory and apoptotic genes. We have identified potential pathways, via interferon regulatory factor 3 (IRF3) activation or
Hoxa13
,
Polr2a
,
Nr4a1
, or
Ing1
induction, that contribute to this redundancy. This study illustrates another way in which the host has evolved to establish several overlapping mechanisms to respond to viral infections.
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Details
- Title
- The Alpha/Beta Interferon Receptor Provides Protection against Influenza Virus Replication but Is Dispensable for Inflammatory Response Signaling
- Creators
- Alan G Goodman - Department of Microbiology, University of WashingtonHui Zeng - Department of Microbiology, University of WashingtonSean C Proll - Department of Microbiology, University of WashingtonXinxia Peng - Department of Microbiology, University of WashingtonCristian Cillóniz - Department of Microbiology, University of WashingtonVictoria S Carter - Department of Microbiology, University of WashingtonMarcus J Korth - Department of Microbiology, University of WashingtonTerrence M Tumpey - Department of Microbiology, University of WashingtonMichael G Katze - Department of Microbiology, University of Washington
- Publication Details
- Journal of virology, Vol.84(4), pp.2027-2037
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- American Society for Microbiology (ASM)
- Identifiers
- 99900547663801842
- Language
- English
- Resource Type
- Journal article