{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:57:40Z","timestamp":1790517460491,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["98-2311-B-182-003"],"award-info":[{"award-number":["98-2311-B-182-003"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["101-2321-B-001-013"],"award-info":[{"award-number":["101-2321-B-001-013"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005795","name":"Chang Gung Memorial Hospital, Linkou","doi-asserted-by":"publisher","award":["CMRPD1B0423"],"award-info":[{"award-number":["CMRPD1B0423"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005795","name":"Chang Gung Memorial Hospital, Linkou","doi-asserted-by":"publisher","award":["CMRPD1D0322"],"award-info":[{"award-number":["CMRPD1D0322"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Enterovirus 71 (EV71), a member of\n            <jats:named-content content-type=\"genus-species\">Picornaviridae<\/jats:named-content>\n            , is associated with severe central nervous system complications. In this study, we identified a cellular microRNA (miRNA), miR-197, whose expression was downregulated by viral infection in a time-dependent manner. In miR-197 mimic-transfected cells, EV71 replication was inhibited, whereas the internal ribosome entry site (IRES) activity was decreased in EV71 strains with or without predicted miR-197 target sites, indicating that miR-197 targets host proteins to modulate viral replication. We thus used a quantitative proteomics approach, aided by the TargetScan algorithm, to identify putative target genes of miR-197. Among them, RAN was selected and validated as a genuine target in a 3\u2032 untranslated region (UTR) reporter assay. Reduced production of RAN by RNA interference markedly reduced the synthesis of EV71-encoded viral proteins and virus titers. Furthermore, reintroduction of nondegradable RAN into these knockdown cells rescued viral protein synthesis. miR-197 levels were modulated by EV71 to maintain RAN mRNA translatability at late times postinfection since we demonstrated that cap-independent translation exerted by its intrinsic IRES activity was occurring at times when translation attenuation was induced by EV71. EV71-induced downregulation of miR-197 expression increased the expression of RAN, which supported the nuclear transport of the essential viral proteins 3D\/3CD and host protein hnRNP K for viral replication. Our data suggest that downregulation of cellular miRNAs may constitute a newly identified mechanism that sustains the expression of host proteins to facilitate viral replication.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Enterovirus 71 (EV71) is a picornavirus with a positive-sense single-stranded RNA that globally inhibits the cellular translational system, mainly by cleaving cellular eukaryotic translation initiation factor 4G (eIF4G) and poly(A)-binding protein (PABP), which inhibits the association of the ribosome with the host capped mRNA. We used a microRNA (miRNA) microarray chip to identify the host miRNA 197 (miR-197) that was downregulated by EV71. We also used quantitative mass spectrometry and a target site prediction tool to identify the miR-197 target genes. During viral infection, the expression of the target protein RAN was upregulated considerably, and there was a parallel downregulation of miR-197. The nuclear transport of viral 3D\/3CD protein and of the host proteins involved in viral replication proceeded in an RAN-dependent manner. We have identified a new mechanism in picornavirus through which EV71-induced cellular miRNA downregulation can regulate host protein levels to facilitate viral replication.\n          <\/jats:p>","DOI":"10.1128\/jvi.02143-15","type":"journal-article","created":{"date-parts":[[2015,11,19]],"date-time":"2015-11-19T03:34:17Z","timestamp":1447904057000},"page":"1424-1438","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Host MicroRNA miR-197 Plays a Negative Regulatory Role in the Enterovirus 71 Infectious Cycle by Targeting the RAN Protein"],"prefix":"10.1128","volume":"90","author":[{"given":"Wen-Fang","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Yi","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo-Yun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kean-Seng","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Rong","family":"Jheng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hsun","family":"Chiu","sequence":"additional","affiliation":[{"name":"Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzong-Yuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Yung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim-Tong","family":"Horng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan"},{"name":"Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan"},{"name":"Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm952"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.082701.108"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.23.090506.123406"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.06.017"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2002.tb00601.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000593"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01434.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/13550280490521032"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.04.076"},{"key":"e_1_3_3_11_2","first-page":"795","volume-title":"Fields virology","author":"Racaniello VR","year":"2007","unstructured":"Racaniello VR. 2007. Picornaviridae: the viruses and their replication, p 795\u2013838. In Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE (ed), Fields virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"5"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134243"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm1080"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.244"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.12.001"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02655-12"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07242"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07228"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl590"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-3-18"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02476-08"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn901"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611145200"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl1009"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0309-228"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.6"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05063-11"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605375103"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2008.00876.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004686"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00594"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(03)00165-5"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2003.10.020"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.2008\/003673-0"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1226191"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.57.2.638-646.1986"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj135"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)01018-3"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079288"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02143-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02143-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T14:16:02Z","timestamp":1646489762000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.02143-15"}},"subtitle":[],"editor":[{"given":"S.","family":"L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,2]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1128\/JVI.02143-15"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02143-15","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2]]},"assertion":[{"value":"2015-08-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}