Study of STAT1 knockout mice increasing sensitivity in EV71 infection
LI Guangchao ZHANG Qian WU Jing ZHAO Binbin CHEN Xin QIN Chuan LIU Jiangning▲
Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences Peking Union Medicine College Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health Key Laboratory of Human Diseases Animal Models，State Administration of Traditional Chinese Medicine, Beijing 100021, China
Abstract：Objective To analyze the differential expression of immune-associated factors in STAT1 knockout mice, and observe the symptoms and viral load after EV71 virus infection, in order to provide a data base for anti-EV71 therapy. Methods Cytometric bead assay (CBA) was used to quantitative analysis the levels of serum immune-associated factors in STAT1 knockout mice after LPS-induced treatment. The symptom and tissue pathological features were observed and the level of muscle virus RNA was quantitated by real-time PCR in STAT1 knockout mice after EV71 virus infection. Results The levels of multi- immune-associated factors were decreased in STAT1 knockout mice after LPS stimulating (P ＜ 0.01), and pathological damage was aggravated accompanied by the higher viral load in muscle (P ＜ 0.01), also severe symptoms and higher mortality when compared to wide type mice after EV71 infection. Conclusions STAT1 plays an important role in the immune responseafter EV71 infection.Thus, STAT1 gene deletion can improve the sensitivity of mice to EV71 virus.
[1] Lu J，Zeng H，Zheng H，et al. Hand，foot and mouth disease in Guangdong，China，in 2013：new trends in the continuing epidemic [J]. Clin Microbiol Infect，2014，20（7）：442-445.
[2] Teng S，Wei Y，Zhao SY，et al. Intestinal detoxification time of hand-foot-and-mouth disease in children with EV71 infection and the related factors [J]. World J Pediatr，2015， 11（4）：380-385.
[3] Shen J，Zhao C，Cao P，et al. Relationship between serologic response and clinical symptoms in children with enterovirus 71-infected hand-foot-mouth disease [J]. Int J Clin Exp Pathol，2015，8（9）：11608-11614.
[4] Huang HI，Chang YY，Lin JY，et al.Interactome analysis of the EV71 5' untranslated region in differentiated neuronal cells SH-SY5Y and regulatory role of FBP3 in viral replication [J]. Proteomics，2016，16（17）：2351-2362.
[5] 隋美丽，李懿，刘新奎，等.手足口病流行病学-病原学及重症化机制的研究进展[J].中国病原生物学杂志，2017， 12（1）：92-98.
[6] Catalfamo M，Cecile LS，Luckey MA，et al. Overexpression of total STAT1 during lymphopenia-induced proliferation leads to decrease CD4 T cell survival [J]. J Immunol，2016， 196（1 Supplement）：55-56.
[7] Hsu KS，Zhao X，Cheng X，et al. Dual regulation of Stat1 and Stat3 by the tumor suppressor protein PML contributes to IFNα-mediated inhibition of angiogenesis [J]. J Biol Chem，2017：jbc.M116.771071.
[8] Lee SH，Kwak CH，Lee SK，et al. Anti-inflammatory effect of ascochlorin in LPS-stimulated RAW 264.7 macrophage cells is accompanied with the down-regulation of iNOS，COX-2 and proinflammatory cytokines through NF-κB，ERK1/2，and p38 signaling pathway [J]. J Cell Biochem，2016，117（4）：978-987.
[9] Luu K，Greenhill CJ，Majoros A，et al. STAT1 plays a role in TLR signal transduction and inflammatory responses [J]. Immunol Cell Biol，2014，92（9）：761-769.
[10] Zou R，Zhang G，Li S，et al. A functional polymorphism in IFNAR1 gene is associated with susceptibility and severity of HFMD with EV71 infection [J]. Sci Rep，2015， 2015：5.
[11] 李圆圆，史伟峰，史梅，等. JAK/STAT信号通路对肠道病毒71型感染的调控作用[J].临床检验杂志，2015，33（9）：683-686.
[12] Wang LC，Chen SO，Chang SP，et al. Enterovirus 71 proteins 2A and 3D antagonize the antiviral activity of Gamma interferon via signaling attenuation [J]. J Virol，2015， 89（14）：7028-7037.
[13] Pathinayake PS，Hsu ACY，Wark PAB. innate immunity and immune evasion by Enterovirus 71 [J]. Viruses，2015，7（12）：6613-6630.
[14] Xiu J，Zhu H，Xu Y，et al. Necrotizing myositis causes restrictive hypoventilation in a mouse model for human enterovirus 71 infection [J]. Virol J，2013，10（1）：215.
[15] Lee HH，Shin JS，Lee WS，et al. Biflorin，isolated from the flower buds of Syzygiumaromaticum L.，suppresses LPS-induced inflammatory mediators via STAT1 inactivation in macrophages and protects mice from endotoxin shock [J]. J Nat Products，2016，79（4）：711-720.
[16] Kim S，Koga T，Isobe M，et al. Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation [J]. Genes Development，2003，17（16）：1979-1991.
[17] Chaudhuri A，Yang B，Gendelman HE，et al. STAT1 signaling modulates HIV-1-induced inflammatory responses and leukocyte transmigration across the blood-brain barrier [J]. Blood，2008，111（4）：2062-2072.
[18] Matikainen S，Pirhonen J，Miettinen M，et al. Influenza A and sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages [J]. Virology，2000，276（1）：138-147.
[19] Swierkot J，Nowak B，Czarny A，et al. The activity of JAK/STAT and NF-κB in patients with rheumatoid arthritis [J]. Advances Clin Expe Med，2016，25（4）：709-717.
[20] Lee C，Lim HK，Sakong J，et al. Janus kinase-signal transducer and activator of transcription mediates phosphatidic acid-induced interleukin （IL）-1β and IL-6 production [J]. Mol Pharmacol，2006，69（3）：1041-1047.
2017, Vol. 14 
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