Both RIG-I and MDA5 RNA helicases contribute to the induction of alpha/beta interferon in measles virus-infected human cells.
Measles virus (MV), a member of the family Paramyxoviridae, is a nonsegmented negative-strand RNA virus. The RNA helicases retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are differentially involved in the detection of cytoplasmic viral RNAs and induction of alpha/beta interferon (IFN-alpha/beta). RIG-I is generally believed to play a major role in the recognition of paramyxoviruses, whereas many viruses of this family produce V proteins that can inhibit MDA5. To determine the individual roles of MDA5 and RIG-I in IFN induction after MV infection, small interfering RNA-mediated knockdown of MDA5 or RIG-I was performed in the human epithelial cell line H358, which is susceptible to wild-type MV isolates. The production of IFN-beta mRNA in response to MV infection was greatly reduced in RIG-I knockdown clones compared to that in H358 cells, confirming the importance of RIG-I in the detection of MV. The IFN-beta mRNA levels were also moderately reduced in MDA5 knockdown clones, even though these clones retained fully functional RIG-I. A V protein-deficient recombinant MV (MVDeltaV) induced higher amounts of IFN-beta mRNA at the early stage of infection in H358 cells compared to the parental virus. The reductions in the IFN-beta mRNA levels in RIG-I knockdown clones were less pronounced after infection with MVDeltaV than after infection with the parental virus. Taken together, the present results indicate that RIG-I and MDA5 both contribute to the recognition of MV and that the V protein promotes MV growth at least partly by inhibiting the MDA5-mediated IFN responses.
Department of Virology, Kyushu University, Fukuoka 812-8582, Japan.
Satoshi
S
Ikegame
Makoto
M
Takeda
Shinji
S
Ohno
Yuichiro
Y
Nakatsu
Yoichi
Y
Nakanishi
Yusuke
Y
Yanagi
D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D000072640:Interferon-Induced Helicase, IFIH1; D016898:Interferon-alpha / Q000235:genetics; D016899:Interferon-beta / Q000235:genetics; D008459:Measles virus / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000502:physiology
D007370:Interferon Type I; D016898:Interferon-alpha; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D014764:Viral Proteins; D016899:Interferon-beta; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1