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2017 ; 8
(ä): 189
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MDA5 Induces a Stronger Interferon Response than RIG-I to GCRV Infection through
a Mechanism Involving the Phosphorylation and Dimerization of IRF3 and IRF7 in
CIK Cells
#MMPMID28286505
Wan Q
; Yang C
; Rao Y
; Liao Z
; Su J
Front Immunol
2017[]; 8
(ä): 189
PMID28286505
show ga
Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated
gene 5 (MDA5) are critical cytosolic sensors that trigger the production of
interferons (IFNs). Though their recognition functions are well identified, their
unique roles in the downstream signal transduction remain to be elucidated.
Herein, we report the differential effect between grass carp (Ctenopharyngodon
idella) MDA5 (CiMDA5) and CiRIG-I on the production of various IFNs upon grass
carp reovirus (GCRV) infection in C. idella kidney (CIK) cell line. In CIK cells,
grass carp IFN1 (CiIFN1) and CiIFN3 are relatively highly expressed while CiIFN2
and CiIFN4 are relatively slightly expressed. Following GCRV infection, CiMDA5
induces a more extensive type I IFN response than CiRIG-I. Further investigation
reveals that both CiMDA5 and CiRIG-I facilitate the expression and total
phosphorylation levels of grass carp IFN regulatory factor (IRF) 3 (CiIRF3) and
CiIRF7 upon GCRV infection or poly(I:C) stimulation. However, the difference is
that CiRIG-I decreases the threonine phosphorylation level of CiIRF7. As a
consequence, CiMDA5 enhances the heterodimerization of CiIRF3 and CiIRF7 and
homodimerization of CiIRF7, whereas CiRIG-I facilitates the heterodimerization
but attenuates homodimerization of CiIRF7. Moreover, the present study suggests
that CiIRF3 and CiIRF7 heterodimers and CiIRF7 homodimers are able to induce more
extensive IFN-I responses than CiIRF3 homodimers under GCRV infection.
Additionally, CiMDA5 induces a stronger type II IFN (IFN-II) response against
GCRV infection than CiRIG-I. Collectively, these results demonstrate that CiMDA5
plays a more potent role than CiRIG-I in IFN response to GCRV infection through
differentially regulating the phosphorylation and dimerization of CiIRF3 and
CiIRF7.