Differential type I IFN-inducing abilities of wild-type versus vaccine strains of measles virus.
Laboratory adapted and vaccine strains of measles virus (MV) induced type I IFN in infected cells. The wild-type strains in contrast induced it to a far lesser extent. We have investigated the mechanism for this differential type I IFN induction in monocyte-derived dendritic cells infected with representative MV strains. Laboratory adapted strains Nagahata and Edmonston infected monocyte-derived dendritic cells and activated IRF-3 followed by IFN-beta production, while wild-type MS failed to activate IRF-3. The viral IRF-3 activation is induced within 2 h, an early response occurring before protein synthesis. Receptor usage of CD46 or CD150 and nucleocapsid (N) protein variations barely affected the strain-to-strain difference in IFN-inducing abilities. Strikingly, most of the IFN-inducing strains possessed defective interference (DI) RNAs of varying sizes. In addition, an artificially produced DI RNA consisting of stem (the leader and trailer of MV) and loop (the GFP sequence) exhibited potential IFN-inducing ability. In this case, however, cytoplasmic introduction was needed for DI RNA to induce type I IFN in target cells. By gene-silencing analysis, DI RNA activated the RIG-I/MDA5-mitochondria antiviral signaling pathway, but not the TLR3-TICAM-1 pathway. DI RNA-containing strains induced IFN-beta mRNA within 2 h while the same recombinant strains with no DI RNA required >12 h postinfection to attain similar levels of IFN-beta mRNA. Thus, the stem-loop structure, rather than full genome replication or specific internal sequences of the MV genome, is required for an early phase of type I IFN induction by MV in host cells.
Shingai
Masashi
M
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Ebihara
Takashi
T
Begum
Nasim A
NA
Kato
Atsushi
A
Honma
Toshiki
T
Matsumoto
Kenji
K
Saito
Hirohisa
H
Ogura
Hisashi
H
Matsumoto
Misako
M
Seya
Tsukasa
T
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D000072640:Interferon-Induced Helicase, IFIH1; D008458:Measles Vaccine / Q000235:genetics / Q000276:immunology*; D008459:Measles virus / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction
C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D008458:Measles Vaccine; D012367:RNA, Viral; D023062:Receptors, Interleukin-8A; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D051550:I-kappa B Kinase; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1