Sendai virus targets inflammatory responses, as well as the interferon-induced antiviral state, in a multifaceted manner.
We have used cDNA arrays to compare the activation of various cellular genes in response to infection with Sendai viruses (SeV) that contain specific mutations. Three groups of cellular genes activated by mutant SeV infection, but not by wild-type SeV, were identified in this way. While some of these genes are well known interferon (IFN)-stimulated genes, others, such as those for interleukin-6 (IL-6) and IL-8, are not directly induced by IFN. The gene for beta IFN (IFN-beta), which is critical for initiating an antiviral response, was also specifically activated in mutant SeV infections. The SeV-induced activation of IFN-beta was found to depend on IFN regulatory factor 3, and the activation of all three cellular genes was independent of IFN signaling. Mutations that disrupt four distinct elements in the SeV genome (the leader RNA, two regions of the C protein, and the V protein) all lead to enhanced levels of IFN-beta mRNA, and at least three of these viral genes also appear to be involved in preventing activation of IL-8. Our results suggest that SeV targets the inflammatory and adaptive immune responses as well as the IFN-induced intracellular antiviral state by using a multifaceted approach.
Strähle
Laura
L
Department of Genetics and Microbiology, University of Geneva School of Medicine, CMU, 9 Avenue de Champel, CH-1211 Geneva, Switzerland.
Garcin
Dominique
D
Le Mercier
Philippe
P
Schlaak
Joerg F
JF
Kolakofsky
Daniel
D
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007110:Immunity, Active; D007249:Inflammation; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000235:genetics / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D029082:Sendai virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D015850:Interleukin-6; D016209:Interleukin-8; D014157:Transcription Factors; D014764:Viral Proteins; C051221:nonstructural C protein, Sendai virus; D016899:Interferon-beta; D007372:Interferons