Giuseppe
Emeritus
J Virol. 2009 Nov 25. [Epub ahead of print]
THE INTERFERON{alpha}/{beta} RECEPTOR PROVIDES PROTECTION AGAINST INFLUENZA VIRUS REPLICATION BUT IS DISPENSABLE FOR INFLAMMATORY RESPONSE SIGNALING.
Goodman AG, Zeng H, Proll SC, Peng X, Cilloniz C, Carter VS, Korth MJ, Tumpey TM, Katze MG. - Department of Microbiology, University of Washington, Washington National Primate Research Center, Seattle, WA 98195; Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, 30333.
The innate immune response provides the first line of defense against foreign pathogens by responding to molecules which 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 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 in mouse embryonic fibroblasts lacking the interferon-alpha/beta receptor, the interferon-gamma receptor, or both. In the absence of the interferon-alpha/beta receptor, we observed increased viral replication but decreased activation of PKR, Stat1, and NF-kappaB; the presence or absence of the interferon-gamma receptor did not exhibit discernable differences of these readouts. Analysis of gene expression profiles showed that while cells lacking the interferon-alpha/beta receptor exhibited decreased transcription of antiviral genes, genes related to inflammatory and apoptotic responses were transcribed to similar levels as cells containing the receptor. These results indicate that while the interferon-alpha/beta 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 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.
PMID: 19939913 [PubMed - as supplied by publisher]
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THE INTERFERON{alpha}/{beta} RECEPTOR PROVIDES PROTECTION AGAINST INFLUENZA VIRUS REPLICATION BUT IS DISPENSABLE FOR INFLAMMATORY RESPONSE SIGNALING.
Goodman AG, Zeng H, Proll SC, Peng X, Cilloniz C, Carter VS, Korth MJ, Tumpey TM, Katze MG. - Department of Microbiology, University of Washington, Washington National Primate Research Center, Seattle, WA 98195; Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, 30333.
The innate immune response provides the first line of defense against foreign pathogens by responding to molecules which 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 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 in mouse embryonic fibroblasts lacking the interferon-alpha/beta receptor, the interferon-gamma receptor, or both. In the absence of the interferon-alpha/beta receptor, we observed increased viral replication but decreased activation of PKR, Stat1, and NF-kappaB; the presence or absence of the interferon-gamma receptor did not exhibit discernable differences of these readouts. Analysis of gene expression profiles showed that while cells lacking the interferon-alpha/beta receptor exhibited decreased transcription of antiviral genes, genes related to inflammatory and apoptotic responses were transcribed to similar levels as cells containing the receptor. These results indicate that while the interferon-alpha/beta 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 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.
PMID: 19939913 [PubMed - as supplied by publisher]
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