{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:57:34Z","timestamp":1790517454928,"version":"4.1.0"},"reference-count":115,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2015,12,14]],"date-time":"2015-12-14T00:00:00Z","timestamp":1450051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Enterovirus 71 (EV71) is a major infectious disease affecting millions of people worldwide and it is the main etiological agent for outbreaks of hand foot and mouth disease (HFMD). Infection is often associated with severe gastroenterological, pulmonary, and neurological diseases that are most prevalent in children. Currently, no effective vaccine or antiviral drugs exist against EV71 infection. A lack of knowledge on the molecular mechanisms of EV71 infection in the host and the virus-host interactions is a major constraint to developing specific antiviral strategies against this infection. Previous studies have identified and characterized the function of several viral proteins produced by EV71 that interact with the host innate immune proteins, including type I interferon signaling and microRNAs. These interactions eventually promote efficient viral replication and increased susceptibility to the disease. In this review we discuss the functions of EV71 viral proteins in the modulation of host innate immune responses to facilitate viral replication.<\/jats:p>","DOI":"10.3390\/v7122961","type":"journal-article","created":{"date-parts":[[2015,12,14]],"date-time":"2015-12-14T10:21:33Z","timestamp":1450088493000},"page":"6613-6630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Innate Immunity and Immune Evasion by Enterovirus 71"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4947-5918","authenticated-orcid":false,"given":"Prabuddha","family":"Pathinayake","sequence":"first","affiliation":[{"name":"Priority Research Centre for Asthma and Respiratory Disease, University of Newcastle and Hunter Medical Research Institute, New South Wales 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Hsu","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Asthma and Respiratory Disease, University of Newcastle and Hunter Medical Research Institute, New South Wales 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Wark","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Asthma and Respiratory Disease, University of Newcastle and Hunter Medical Research Institute, New South Wales 2305, Australia"},{"name":"Department of Respiratory and Sleep Medicine, John Hunter Hospital, New South Wales 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,14]]},"reference":[{"key":"ref_1","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_2","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_3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/B978-0-12-387664-5.00003-0","article-title":"The control of adaptive immune responses by the innate immune system","volume":"109","author":"Schenten","year":"2011","journal-title":"Adv. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3109\/08830185.2010.529976","article-title":"Pathogen recognition by the innate immune system","volume":"30","author":"Kumar","year":"2011","journal-title":"Int. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s10156-008-0596-1","article-title":"Pathogen recognition by innate receptors","volume":"14","author":"Kumagai","year":"2008","journal-title":"J. Infect. Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.immuni.2011.05.006","article-title":"Toll-like receptors and their crosstalk with other innate receptors in infection and immunity","volume":"34","author":"Kawai","year":"2011","journal-title":"Immunity"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.18295\/2075-0528.1648","article-title":"The Role of Damage-Associated Molecular Patterns in Human Diseases: Part I\u2014Promoting inflammation and immunity","volume":"15","author":"Land","year":"2015","journal-title":"Sultan Qaboos Univ. Med. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1600-065X.2008.00737.x","article-title":"Innate immunity to virus infection","volume":"227","author":"Takeuchi","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.coi.2007.09.002","article-title":"The inflammasome: A danger sensing complex triggering innate immunity","volume":"19","author":"Petrilli","year":"2007","journal-title":"Curr. Opin. Immunol."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S1386-6532(00)00068-8","article-title":"An outbreak of enterovirus 71 infection in Taiwan, 1998: Epidemiologic and clinical manifestations","volume":"17","author":"Liu","year":"2000","journal-title":"J. Clin. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1097\/00006454-200008000-00017","article-title":"Enterovirus 71 infections at a Canadian center","volume":"19","author":"Merovitz","year":"2000","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e0119173","DOI":"10.1371\/journal.pone.0119173","article-title":"Enterovirus 71 infection causes severe pulmonary lesions in gerbils, merionesunguiculatus, which can be prevented by passive immunization with specific antisera","volume":"10","author":"Xu","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1038\/labinvest.2011.82","article-title":"Pathogenesis study of enterovirus 71 infection in rhesus monkeys","volume":"91","author":"Zhang","year":"2011","journal-title":"Lab. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Huang, S.W., Lee, Y.P., Hung, Y.T., Lin, C.H., Chuang, J.I., Lei, H.Y., Su, I.J., and Yu, C.K. (2011). Exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice. Respir. Res., 12.","DOI":"10.1186\/1465-9921-12-147"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1126\/science.1132505","article-title":"5\u2032-Triphosphate RNA is the ligand for RIG-I","volume":"314","author":"Hornung","year":"2006","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature04734","article-title":"Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses","volume":"441","author":"Kato","year":"2006","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.celrep.2012.10.005","article-title":"MDA5 detects the double-stranded RNA replicative form in picornavirus-infected cells","volume":"2","author":"Feng","year":"2012","journal-title":"Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/ni1087","article-title":"The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses","volume":"5","author":"Yoneyama","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.4049\/jimmunol.175.5.2851","article-title":"Shared and unique functions of the DExD\/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity","volume":"175","author":"Yoneyama","year":"2005","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1084\/jem.20080091","article-title":"Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5","volume":"205","author":"Kato","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.cell.2005.08.012","article-title":"Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-\u03baB and IRF 3","volume":"122","author":"Seth","year":"2005","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Potter, J.A., Randall, R.E., and Taylor, G.L. (2008). Crystal structure of human IPS-1\/MAVS\/VISA\/Cardifcaspase activation recruitment domain. BMC Struct. Biol., 8.","DOI":"10.1186\/1472-6807-8-11"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ni921","article-title":"IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway","volume":"4","author":"Fitzgerald","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.coi.2008.01.002","article-title":"MDA5\/RIG-I and virus recognition","volume":"20","author":"Takeuchi","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mito.2010.08.006","article-title":"Mitochondria and viruses","volume":"11","author":"Ohta","year":"2011","journal-title":"Mitochondrion"},{"key":"ref_27","first-page":"343","article-title":"NF-kappaB and its regulation on the immune system","volume":"1","author":"Liang","year":"2004","journal-title":"Cell. Mol. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5320","DOI":"10.4049\/jimmunol.1101503","article-title":"The TLR3\/TICAM-1 pathway is mandatory for innate immune responses to poliovirus infection","volume":"187","author":"Oshiumi","year":"2011","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1128\/JVI.05245-11","article-title":"The toll-like receptor 3-mediated antiviral response is important for protection against poliovirus infection in poliovirus receptor transgenic mice","volume":"86","author":"Abe","year":"2012","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e4127","DOI":"10.1371\/journal.pone.0004127","article-title":"Toll-like receptor 3 signaling on macrophages is required for survival following coxsackievirus B4 infection","volume":"4","author":"Richer","year":"2009","journal-title":"PLoS ONE"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"20446","DOI":"10.1073\/pnas.0810372105","article-title":"A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity","volume":"105","author":"Negishi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nature04369","article-title":"Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6","volume":"439","author":"Hacker","year":"2006","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.immuni.2012.03.013","article-title":"The JAK-STAT pathway at twenty","volume":"36","author":"Stark","year":"2012","journal-title":"Immunity"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nri3581","article-title":"Regulation of type I interferon responses","volume":"14","author":"Ivashkiv","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nm.1992","article-title":"Scavenger receptor B2 is a cellular receptor for enterovirus 71","volume":"15","author":"Yamayoshi","year":"2009","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/1743-422X-6-141","article-title":"Sialylatedglycans as receptor and inhibitor of enterovirus 71 infection to DLD-1 intestinal cells","volume":"6","author":"Yang","year":"2009","journal-title":"Virol. J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lin, J.Y., Chen, T.C., Weng, K.F., Chang, S.C., Chen, L.L., and Shih, S.R. (2009). Viral and host proteins involved in picornavirus life cycle. J. Biomed. Sci., 16.","DOI":"10.1186\/1423-0127-16-103"},{"key":"ref_38","first-page":"345","article-title":"Human type I interferons: Structure and function","volume":"38","author":"Kontsek","year":"1994","journal-title":"ActaVirol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1097\/00001622-200311000-00005","article-title":"Interferons: Mechanisms of action and clinical applications","volume":"15","author":"Parmar","year":"2003","journal-title":"Curr. Opin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1111\/j.1462-5822.2006.00716.x","article-title":"Interferon signalling network in innate defence","volume":"8","author":"Takaoka","year":"2006","journal-title":"Cell. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nri2314","article-title":"Interferon-inducible antiviral effectors","volume":"8","author":"Sadler","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3851\/IMP1720","article-title":"Potent inhibition of human enterovirus 71 replication by type I interferon subtypes","volume":"16","author":"Yi","year":"2011","journal-title":"Antivir. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1099\/vir.0.81195-0","article-title":"Type I interferons protect mice against enterovirus 71 infection","volume":"86","author":"Liu","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1093\/infdis\/jir174","article-title":"Synergistic inhibition of enterovirus 71 replication by interferon and rupintrivir","volume":"203","author":"Hung","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1128\/JVI.06687-11","article-title":"Enterovirus 71 disrupts interferon signaling by reducing the level of interferon receptor 1","volume":"86","author":"Lu","year":"2012","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/ni875","article-title":"IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex","volume":"4","author":"Kotenko","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1128\/JVI.80.9.4501-4509.2006","article-title":"Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo","volume":"80","author":"Ank","year":"2006","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1089\/jir.2006.26.373","article-title":"IFN-lambda: Novel antiviral cytokines","volume":"26","author":"Ank","year":"2006","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7944","DOI":"10.1073\/pnas.1100552108","article-title":"IFN-lambda determines the intestinal epithelial antiviral host defense","volume":"108","author":"Pott","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/cei.12368","article-title":"Type III interferons are expressed by Coxsackievirus-infected human primary hepatocytes and regulate hepatocyte permissiveness to infection","volume":"177","author":"Lind","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7646","DOI":"10.1128\/JVI.03431-12","article-title":"Induction of an antiviral state and attenuated coxsackievirus replication in type III interferon-treated primary human pancreatic islets","volume":"87","author":"Lind","year":"2013","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.jmb.2011.03.007","article-title":"Crystal structure of human enterovirus 71 3C protease","volume":"408","author":"Cui","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF02256567","article-title":"Mutations at KFRDI and VGK domains of enterovirus 71 3C protease affect its RNA binding and proteolytic activities","volume":"11","author":"Shih","year":"2004","journal-title":"J. Biomed. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.virol.2005.06.047","article-title":"RNA interference against enterovirus 71 infection","volume":"341","author":"Sim","year":"2005","journal-title":"Virology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7348","DOI":"10.1128\/JVI.03541-12","article-title":"Conformational plasticity of the 2A proteinase from enterovirus 71","volume":"87","author":"Cai","year":"2013","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e63431","DOI":"10.1371\/journal.pone.0063431","article-title":"MDA5 plays a crucial role in enterovirus 71 RNA-mediated IRF3 activation","volume":"8","author":"Kuo","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1128\/JVI.00631-09","article-title":"MDA5 and MAVS mediate type I interferon responses to coxsackie B virus","volume":"84","author":"Wang","year":"2010","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.virol.2010.02.010","article-title":"Melanoma differentiation-associated protein-5 (MDA-5) limits early viral replication but is not essential for the induction of type 1 interferons after Coxsackievirus infection","volume":"401","author":"Huhn","year":"2010","journal-title":"Virology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1128\/JVI.01360-06","article-title":"MDA-5 is cleaved in poliovirus-infected cells","volume":"81","author":"Barral","year":"2007","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.virol.2009.06.045","article-title":"RIG-I is cleaved during picornavirus infection","volume":"391","author":"Barral","year":"2009","journal-title":"Virology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8051","DOI":"10.1128\/JVI.02491-09","article-title":"The 3C protein of enterovirus 71 inhibits retinoid acid-inducible gene I-mediated interferon regulatory factor 3 activation and type I interferon responses","volume":"84","author":"Lei","year":"2010","journal-title":"J. Virol."},{"key":"ref_62","first-page":"e1001178","article-title":"Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium","volume":"6","author":"Slater","year":"2010","journal-title":"PLoSPathog."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"8811","DOI":"10.1128\/JVI.00447-11","article-title":"Cleavage of the adaptor protein TRIF by enterovirus 71 3C inhibits antiviral responses mediated by Toll-like receptor 3","volume":"85","author":"Lei","year":"2011","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1128\/JVI.01855-12","article-title":"Cleavage of interferon regulatory factor 7 by enterovirus 71 3C suppresses cellular responses","volume":"87","author":"Lei","year":"2013","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/ni1303","article-title":"Innate immune recognition of viral infection","volume":"7","author":"Kawai","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/gene.2011.21","article-title":"IRF7: Activation, regulation, modification and function","volume":"12","author":"Ning","year":"2011","journal-title":"Genes Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1074\/jbc.M608867200","article-title":"TAK1-dependent signaling requires functional interaction with TAB2\/TAB3","volume":"282","author":"Besse","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1038\/ni1255","article-title":"Essential function for the kinase TAK1 in innate and adaptive immune responses","volume":"6","author":"Sato","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"9830","DOI":"10.1128\/JVI.01425-14","article-title":"Enterovirus 71 3C inhibits cytokine expression through cleavage of the TAK1\/TAB1\/TAB2\/TAB3 complex","volume":"88","author":"Lei","year":"2014","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1101\/gad.4.12a.2112","article-title":"A multisubunit factor, CstF, is required for polyadenylation of mammalian pre-mRNAs","volume":"4","author":"Takagaki","year":"1990","journal-title":"Genes Dev."},{"key":"ref_72","first-page":"e1000593","article-title":"Enterovirus 71 3C protease cleaves a novel target CstF-64 and inhibits cellular polyadenylation","volume":"5","author":"Weng","year":"2009","journal-title":"PLoSPathog."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0042-6822(02)00127-7","article-title":"Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3\u2032 end processing of cellular pre-mRNAS","volume":"307","author":"Noah","year":"2003","journal-title":"Virology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.coph.2009.05.003","article-title":"microRNAs and the immune response","volume":"9","author":"Tsitsiou","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e102997","DOI":"10.1371\/journal.pone.0102997","article-title":"Enterovirus71 (EV71) utilise host microRNAs to mediate host immune system enhancing survival during infection","volume":"9","author":"Lui","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.chom.2010.12.001","article-title":"Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E","volume":"9","author":"Ho","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0092-8674(88)90485-0","article-title":"A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization","volume":"53","author":"Sukhatme","year":"1988","journal-title":"Cell"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ho, B.C., Yu, I.S., Lu, L.F., Rudensky, A., Chen, H.Y., Tsai, C.W., Chang, Y.L., Wu, C.T., Chang, L.Y., and Shih, S.R. (2014). Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon. Nat. Commun., 5.","DOI":"10.1038\/ncomms4344"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"11356","DOI":"10.1128\/JVI.01400-14","article-title":"Downregulation of microRNA miR-526a by enterovirus inhibits RIG-I-dependent innate immune response","volume":"88","author":"Xu","year":"2014","journal-title":"J. Virol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1099\/vir.0.79789-0","article-title":"Complete genome sequences of all members of the species Human enterovirus A","volume":"85","author":"Oberste","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1099\/0022-1317-83-6-1367","article-title":"Infection with enterovirus 71 or expression of its 2A protease induces apoptotic cell death","volume":"83","author":"Kuo","year":"2002","journal-title":"J. Gen. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6072","DOI":"10.1128\/JVI.02495-05","article-title":"Dissociation of a MAVS\/IPS-1\/VISA\/Cardif-IKKepsilon molecular complex from the mitochondrial outer membrane by hepatitis C virus NS3-4A proteolytic cleavage","volume":"80","author":"Lin","year":"2006","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/nature04193","article-title":"Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus","volume":"437","author":"Meylan","year":"2005","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7253","DOI":"10.1073\/pnas.0611506104","article-title":"Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor","volume":"104","author":"Yang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"11581","DOI":"10.1128\/JVI.01490-09","article-title":"Cleavage of IPS-1 in cells infected with human rhinovirus","volume":"83","author":"Drahos","year":"2009","journal-title":"J. Virol."},{"key":"ref_86","first-page":"e1001311","article-title":"The coxsackievirus B 3C protease cleaves MAVS and TRIF to attenuate host type I interferon and apoptotic signaling","volume":"7","author":"Mukherjee","year":"2011","journal-title":"PLoSPathog."},{"key":"ref_87","first-page":"e1003231","article-title":"Enterovirus 71 protease 2Apro targets MAVS to inhibit anti-viral type I interferon responses","volume":"9","author":"Wang","year":"2013","journal-title":"PLoSPathog."},{"key":"ref_88","first-page":"4761","article-title":"Visualisation of direct interaction of MDA5 and the dsRNA replicative intermediate form of positive strand RNA viruses","volume":"125","author":"Triantafilou","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1128\/JVI.02712-13","article-title":"Enterovirus 2Apro targets MDA5 and MAVS in infected cells","volume":"88","author":"Feng","year":"2014","journal-title":"J. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4412","DOI":"10.1128\/JVI.02177-08","article-title":"Proteinase 2Apro is essential for enterovirus replication in type I interferon-treated cells","volume":"83","author":"Morrison","year":"2009","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e32947","DOI":"10.1371\/journal.pone.0032947","article-title":"Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection","volume":"7","author":"Hsu","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1089\/vim.2013.0127","article-title":"Enterovirus 71 inhibits cellular type I interferon signaling by downregulating JAK1 protein expression","volume":"27","author":"Liu","year":"2014","journal-title":"Viral Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1006\/viro.1998.9171","article-title":"The predominant elF4G-specific cleavage activity in poliovirus-infected HeLa cells is distinct from 2A protease","volume":"245","author":"Bovee","year":"1998","journal-title":"Virology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1006\/viro.1994.1089","article-title":"2A proteinases of coxsackie- and rhinovirus cleave peptides derived from eIF-4 gamma via a common recognition motif","volume":"198","author":"Sommergruber","year":"1994","journal-title":"Virology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"8444","DOI":"10.1128\/jvi.70.12.8444-8450.1996","article-title":"The eIF4G-eIF4E complex is the target for direct cleavage by the rhinovirus 2A proteinase","volume":"70","author":"Haghighat","year":"1996","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0092-8674(00)81318-5","article-title":"NF-\u03baB: Ten years after","volume":"87","author":"Baeuerle","year":"1996","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"6853","DOI":"10.1038\/sj.onc.1203239","article-title":"Activators and target genes of Rel\/NF-\u03baB transcription factors","volume":"18","author":"Pahl","year":"1999","journal-title":"Oncogene"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1038\/sj.onc.1209941","article-title":"Manipulation of the nuclear factor-\u03baB pathway and the innate immune response by viruses","volume":"25","author":"Hiscott","year":"2006","journal-title":"Oncogene"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.4049\/jimmunol.1100285","article-title":"Enterovirus 71 2C protein inhibits TNF-\u03b1-mediated activation of NF-\u03baB by suppressing I\u03baB kinase \u03b2 phosphorylation","volume":"187","author":"Zheng","year":"2011","journal-title":"J. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.antiviral.2012.12.029","article-title":"Rupintrivir is a promising candidate for treating severe cases of enterovirus-71 infection: Evaluation of antiviral efficacy in a murine infection model","volume":"97","author":"Zhang","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.antiviral.2012.12.005","article-title":"Antiviral drug discovery for the treatment of enterovirus 71 infections","volume":"97","author":"Shang","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1128\/AAC.00268-07","article-title":"Investigating Toll-like receptor agonists for potential to treat hepatitis C virus infection","volume":"51","author":"Thomas","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1002\/hep.20839","article-title":"Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection","volume":"42","author":"Horsmans","year":"2005","journal-title":"Hepatology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7269","DOI":"10.1128\/JVI.79.11.7269-7272.2005","article-title":"Toll-like receptor signaling inhibits hepatitis B virus replication in vivo","volume":"79","author":"Isogawa","year":"2005","journal-title":"J. Virol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1073\/pnas.0510801103","article-title":"Activation of anti-hepatitis C virus responses via Toll-like receptor 7","volume":"103","author":"Lee","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2006.07.011","article-title":"Administration of a dual toll-like receptor 7 and toll-like receptor 8 agonist protects against influenza in rats","volume":"73","author":"Hammerbeck","year":"2007","journal-title":"Antivir. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1128\/IAI.73.5.3044-3052.2005","article-title":"Synthetic toll-like receptor 4 agonists stimulate innate resistance to infectious challenge","volume":"73","author":"Cluff","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1128\/JVI.79.5.2910-2919.2005","article-title":"Synthetic double-stranded RNA poly(I:C) combined with mucosal vaccine protects against influenza virus infection","volume":"79","author":"Ichinohe","year":"2005","journal-title":"J. Virol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1016\/j.vaccine.2007.01.051","article-title":"Nucleic acid-based antiviral drugs against seasonal and avian influenza viruses","volume":"25","author":"Wong","year":"2007","journal-title":"Vaccine"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1182\/blood-2005-12-4821","article-title":"Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells","volume":"108","author":"Levy","year":"2006","journal-title":"Blood"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"11658","DOI":"10.1128\/JVI.00867-14","article-title":"Toll-like receptor 9-mediated protection of enterovirus 71 infection in mice is due to the release of danger-associated molecular patterns","volume":"88","author":"Hsiao","year":"2014","journal-title":"J. Virol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1099\/vir.0.067751-0","article-title":"Inhibition of the foot-and-mouth disease virus subgenomic replicon by RNA aptamers","volume":"95","author":"Forrest","year":"2014","journal-title":"J. Gen. Virol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.antiviral.2013.09.004","article-title":"Single-stranded DNA aptamer that specifically binds to the influenza virus NS1 protein suppresses interferon antagonism","volume":"100","author":"Woo","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4460","DOI":"10.1128\/JVI.79.7.4460-4469.2005","article-title":"The \u03b1\/\u03b2 interferon response controls tissue tropism and pathogenicity of poliovirus","volume":"79","author":"Iwasaki","year":"2005","journal-title":"J. Virol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1161\/01.CIR.103.5.756","article-title":"Cardioselective infection with coxsackievirus B3 requires intact type I interferon signaling: Implications for mortality and early viral replication","volume":"103","author":"Wessely","year":"2001","journal-title":"Circulation"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/12\/2961\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:54:02Z","timestamp":1760216042000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/12\/2961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,14]]},"references-count":115,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,12]]}},"alternative-id":["v7122961"],"URL":"https:\/\/doi.org\/10.3390\/v7122961","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,14]]}}}