Retinoic acid inducible gene-I and melanoma differentiation-associated gene 5 are induced but not essential for dengue virus induced type I interferon response.
Dengue viruses (DENVs) are important human pathogens that cause mild dengue fever, and severe dengue hemorrhagic fever/dengue shock syndrome, and no vaccine or antiviral therapy are currently available. At the initial stage of DENV infection, host pattern recognition receptors are responsible for sensing viral proteins or nucleic acids and initiating innate antiviral responses, including the activation of type I interferon (IFN) and proinflammatory cytokines. Two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), are recently identified as cytoplasmic PPRs for virus infection. Here, in this study the involvement of RIG-I and MDA5 in DENV-induced IFN-β response A549 cells were investigated. DENV infection readily up-regulated RIG-I expression, activated IRF-3 and RIG-I mRNA transcription, and induced the production of IFN-β in A549 cells in a strain- and serotype-independent manner. While gene silencing of RIG-I by small interfering RNAs failed to significantly inhibit IFN-β production induced by DENV infection. Further experiments demonstrated that MDA5 was also induced by DENV infection, and MDA5 knockout did not block DENV induced IFN-β production in A549 cells. Our results demonstrated that both RIG-I and MDA5 were induced but neither of the two was essential for DENV induced IFN IFN-β response in A549 cells. These findings suggest that innate immune pathway are involved in the recognition of DENV by human non-immune cells, and provide insights for the understanding of the molecular mechanism for DENV-induced antiviral response.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
Cheng-Feng
CF
Qin
Hui
H
Zhao
Zhong-Yu
ZY
Liu
Tao
T
Jiang
Yong-Qiang
YQ
Deng
Xu-Dong
XD
Yu
Man
M
Yu
E-De
ED
Qin
D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D003715:Dengue / Q000235:genetics / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation
C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D011971:Receptors, Immunologic; 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