Hantaan virus infection induces CXCL10 expression through TLR3, RIG-I, and MDA-5 pathways correlated with the disease severity.
Hantaan virus (HTNV) is a major agent causing hemorrhagic fever with renal syndrome (HFRS). Although the pathogenesis of HFRS is unclear, some reports have suggested that the abundant production of proinflammatory cytokines and uncontrolled inflammatory responses may contribute to the development of HFRS. CXCL10 is one of these cytokines and is found to be involved in the pathogenesis of many virus infectious diseases. However, the role of CXCL10 in the pathogenesis of HFRS and the molecular regulation mechanism of CXCL10 in HTNV infection remain unknown. In this study, we report that CXCL10 expresses highly in the HFRS patients' sera and the elevated CXCL10 is positively correlated with the severity of HFRS. We find that HTNV, a single-strand RNA virus, can act as a double-strand RNA to activate the TLR3, RIG-I, and MDA-5 signaling pathways. Through the downstream transcription factors of these pathways, NF-κB and IRF7, which bind directly to the CXCL10's promoter, the expression of CXCL10 is increased. Our results may help to better understand the role of CXCL10 in the development of HFRS and may provide some novel insights into the immune response of HTNV infection.
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Yusi
0000-0003-4272-857X
Y
Zhang
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Bei
B
Liu
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Ying
Y
Ma
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China ; Department of Blood Transfusion, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Jing
J
Yi
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Chunmei
C
Zhang
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Yun
Y
Zhang
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Zhuwei
Z
Xu
Department of Infectious Disease, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Jiuping
J
Wang
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Kun
K
Yang
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Angang
A
Yang
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Ran
0000-0002-3614-0422
R
Zhuang
Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Boquan
B
Jin
D000818:Animals; D054357:Chemokine CXCL10 / Q000378:metabolism*; D002522:Chlorocebus aethiops; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D018450:Disease Progression; D018063:Hantaan virus; D006480:Hemorrhagic Fever with Renal Syndrome / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D008156:Luciferases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014709:Vero Cells
C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D016328:NF-kappa B; D054367:Receptors, CXCR3; D011971:Receptors, Immunologic; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D008156:Luciferases; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1