{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:58:37Z","timestamp":1791388717809,"version":"4.3.3"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T00:00:00Z","timestamp":1577059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81730061"],"award-info":[{"award-number":["81730061"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31800147"],"award-info":[{"award-number":["31800147"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Province \u201cPearl River Talent Plan\u201d Innovation and Entrepreneurship Team Project","award":["2017ZT07Y580"],"award-info":[{"award-number":["2017ZT07Y580"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Enterovirus 71 (EV71) infection causes hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby presenting a serious risk to public health. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially show that the interleukin enhancer-binding factor 2 (ILF2) reduces EV71 50% tissue culture infective dose (TCID50) and attenuates EV71 plaque-formation unit (PFU), thereby repressing EV71 infection. Microarray data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) -differentiated macrophages and human rhabdomyosarcoma (RD) cells. In addition, EV71 nonstructural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm, and it colocalizes with 2B in the cytoplasm. Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein.<\/jats:p>","DOI":"10.3390\/v12010022","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T05:56:15Z","timestamp":1577166975000},"page":"22","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects"],"prefix":"10.3390","volume":"12","author":[{"given":"Jing","family":"Jin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Ai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyong","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-2845","authenticated-orcid":false,"given":"Zhen","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailang","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingle","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"},{"name":"Guangdong Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-2895","authenticated-orcid":false,"given":"Jianguo","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"},{"name":"Guangdong Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/S1473-3099(10)70194-8","article-title":"Virology, epidemiology, pathogenesis, and control of enterovirus 71","volume":"10","author":"Solomon","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.coviro.2014.03.007","article-title":"Update on enterovirus 71 infection","volume":"5","author":"Huang","year":"2014","journal-title":"Curr. Opin. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/S1474-4422(10)70209-X","article-title":"Clinical features, diagnosis, and management of enterovirus 71","volume":"9","author":"Ooi","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.micinf.2010.03.006","article-title":"Neural pathogenesis of enterovirus 71 infection","volume":"12","author":"Weng","year":"2010","journal-title":"Microbes Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0168-1702(95)00087-9","article-title":"Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus","volume":"39","author":"Brown","year":"1995","journal-title":"Virus Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1574-6976.2002.tb00601.x","article-title":"An overview of the evolution of enterovirus 71 and its clinical and public health significance","volume":"26","author":"McMinn","year":"2002","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/cr.2011.112","article-title":"DIDS blocks a chloride-dependent current that is mediated by the 2B protein of enterovirus 71","volume":"21","author":"Xie","year":"2011","journal-title":"Cell Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9862","DOI":"10.1128\/JVI.01499-16","article-title":"Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax","volume":"90","author":"Cong","year":"2016","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ao, D., Guo, H.C., Sun, S.Q., Sun, D.H., Fung, T.S., Wei, Y.Q., Han, S.C., Yao, X.P., Cao, S.Z., and Liu, D.X. (2015). Viroporin Activity of the Foot-and-Mouth Disease Virus Non-Structural 2B Protein. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125828"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11106","DOI":"10.1128\/JVI.01310-16","article-title":"Foot-and-Mouth Disease Virus Viroporin 2B Antagonizes RIG-I-Mediated Antiviral Effects by Inhibition of Its Protein Expression","volume":"90","author":"Zhu","year":"2016","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20691","DOI":"10.1016\/S0021-9258(17)32048-3","article-title":"Cloning and expression of cyclosporin A- and FK506-sensitive nuclear factor of activated T-cells: NF45 and NF90","volume":"269","author":"Kao","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.1128\/MCB.05849-11","article-title":"The NF90\/NF45 complex participates in DNA break repair via nonhomologous end joining","volume":"31","author":"Shamanna","year":"2011","journal-title":"Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1038\/emboj.2010.204","article-title":"A multiprotein complex necessary for both transcription and DNA replication at the beta-globin locus","volume":"29","author":"Karmakar","year":"2010","journal-title":"EMBO J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8256","DOI":"10.1074\/jbc.M109.041004","article-title":"NF45 and NF90 regulate HS4-dependent interleukin-13 transcription in T cells","volume":"285","author":"Kiesler","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/cdd.2009.164","article-title":"NF45 functions as an IRES trans-acting factor that is required for translation of cIAP1 during the unfolded protein response","volume":"17","author":"Graber","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1128\/MCB.00546-12","article-title":"Nucleotide composition of cellular internal ribosome entry sites defines dependence on NF45 and predicts a posttranscriptional mitotic regulon","volume":"33","author":"Faye","year":"2013","journal-title":"Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ccell.2017.05.011","article-title":"ILF2 is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma","volume":"32","author":"Marchesini","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.1128\/MCB.01836-08","article-title":"The NF90-NF45 complex functions as a negative regulator in the microRNA processing pathway","volume":"29","author":"Sakamoto","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1128\/MCB.01297-14","article-title":"Overexpression of NF90-NF45 Represses Myogenic MicroRNA Biogenesis, Resulting in Development of Skeletal Muscle Atrophy and Centronuclear Muscle Fibers","volume":"35","author":"Todaka","year":"2015","journal-title":"Mol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21074","DOI":"10.1074\/jbc.M116.748210","article-title":"Suppression of MicroRNA-7 (miR-7) Biogenesis by Nuclear Factor 90-Nuclear Factor 45 Complex (NF90-NF45) Controls Cell Proliferation in Hepatocellular Carcinoma","volume":"291","author":"Higuchi","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s11010-015-2535-7","article-title":"NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma","volume":"410","author":"Wan","year":"2015","journal-title":"Mol. Cell Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"900","DOI":"10.3892\/ijmm.2017.2894","article-title":"MicroRNA-7 functions as a tumor-suppressor gene by regulating ILF2 in pancreatic carcinoma","volume":"39","author":"Bi","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Cheng, S., Jiang, X., Ding, C., Du, C., Owusu-Ansah, K., Weng, X., Hu, W., Peng, C., Lv, Z., and Tong, R. (2016). Expression and Critical Role of Interleukin Enhancer Binding Factor 2 in Hepatocellular Carcinoma. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17081373"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s10735-015-9624-5","article-title":"Upregulated expression of ILF2 in non-small cell lung cancer is associated with tumor cell proliferation and poor prognosis","volume":"46","author":"Ni","year":"2015","journal-title":"J. Mol. Histol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s13277-014-2683-5","article-title":"Expression and clinical role of NF45 as a novel cell cycle protein in esophageal squamous cell carcinoma (ESCC)","volume":"36","author":"Ni","year":"2015","journal-title":"Tumour Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4387081","DOI":"10.1155\/2017\/4387081","article-title":"Expression and Clinical Significance of ILF2 in Gastric Cancer","volume":"2017","author":"Yin","year":"2017","journal-title":"Dis. Markers"},{"key":"ref_27","first-page":"1677","article-title":"Interleukin enhancer binding factor 2 is a prognostic biomarker for breast cancer that also predicts neoadjuvant chemotherapy responses","volume":"10","author":"Jin","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, Y., and Belshan, M. (2016). NF45 and NF90 Bind HIV-1 RNA and Modulate HIV Gene Expression. Viruses, 8.","DOI":"10.3390\/v8020047"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1261\/rna.594207","article-title":"Nuclear factors are involved in hepatitis C virus RNA replication","volume":"13","author":"Isken","year":"2007","journal-title":"RNA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6936","DOI":"10.1128\/JVI.00243-06","article-title":"The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation initiation at the rhinovirus type 2 internal ribosome entry site","volume":"80","author":"Merrill","year":"2006","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.fsi.2018.05.028","article-title":"Eriocheir sinensis microRNA-7 targets crab Myd88 to enhance white spot syndrome virus replication","volume":"79","author":"Huang","year":"2018","journal-title":"Fish. Shellfish Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5176","DOI":"10.1038\/onc.2012.533","article-title":"Induction of p53, p21 and apoptosis by silencing the NF90\/NF45 complex in human papilloma virus-transformed cervical carcinoma cells","volume":"32","author":"Shamanna","year":"2013","journal-title":"Oncogene"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s12985-017-0794-5","article-title":"Interleukin-2 enhancer binding factor 2 interacts with the nsp9 or nsp2 of porcine reproductive and respiratory syndrome virus and exerts negatively regulatory effect on the viral replication","volume":"14","author":"Wen","year":"2017","journal-title":"Virol. J."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wang, W., Xiao, F., Wan, P., Pan, P., Zhang, Y., Liu, F., Wu, K., Liu, Y., and Wu, J. (2017). EV71 3D Protein Binds with NLRP3 and Enhances the Assembly of Inflammasome Complex. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006123"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.bbrc.2018.04.087","article-title":"Interleukin-enhanced binding factor 2 interacts with NLRP3 to inhibit the NLRP3 inflammasome activation","volume":"500","author":"Jin","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","first-page":"493","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Hyg."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Luo, Z., Ge, M., Chen, J., Geng, Q., Tian, M., Qiao, Z., Bai, L., Zhang, Q., Zhu, C., and Xiong, Y. (2017). HRS plays an important role for TLR7 signaling to orchestrate inflammation and innate immunity upon EV71 infection. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006585"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s00011-007-6115-5","article-title":"Optimized THP-1 differentiation is required for the detection of responses to weak stimuli","volume":"56","author":"Park","year":"2007","journal-title":"Inflamm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41467-017-02645-3","article-title":"Zika virus infection induces host inflammatory responses by facilitating NLRP3 inflammasome assembly and interleukin-1beta secretion","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jcv.2006.05.009","article-title":"Modulation of cytokine production by intravenous immunoglobulin in patients with enterovirus 71-associated brainstem encephalitis","volume":"37","author":"Wang","year":"2006","journal-title":"J. Clin. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gong, X., Zhou, J., Zhu, W., Liu, N., Li, J., Li, L., Jin, Y., and Duan, Z. (2012). Excessive proinflammatory cytokine and chemokine responses of human monocyte-derived macrophages to enterovirus 71 infection. BMC Infect. Dis., 12.","DOI":"10.1186\/1471-2334-12-224"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1093\/infdis\/jis446","article-title":"In enterovirus 71 encephalitis with cardio-respiratory compromise, elevated interleukin 1beta, interleukin 1 receptor antagonist, and granulocyte colony-stimulating factor levels are markers of poor prognosis","volume":"206","author":"Griffiths","year":"2012","journal-title":"J. Infect. Dis."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/1\/22\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:45:01Z","timestamp":1760190301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/1\/22"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,23]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["v12010022"],"URL":"https:\/\/doi.org\/10.3390\/v12010022","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,23]]}}}