{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:06:36Z","timestamp":1785189996642,"version":"3.55.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["MR-110-GP-09"],"award-info":[{"award-number":["MR-110-GP-09"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["MR-111-AP-01"],"award-info":[{"award-number":["MR-111-AP-01"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["MR-112-GP-03"],"award-info":[{"award-number":["MR-112-GP-03"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["MR-113-GP-03"],"award-info":[{"award-number":["MR-113-GP-03"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The zinc finger protein 36-like (ZFP36L) family is a CCCH-type group consisting of RNA-binding proteins, i.e., ZFP36L1 and ZFP36L2, which regulate cellular mRNA through the RNA decay pathway. ZFP36L1 combats flavivirus infections through the 5\u2032-3\u2032 XRN1 and 3\u2032-5\u2032 RNA exosome decay pathways. The present study clarified the role of human ZFP36L2 in the defense response of the host against flavivirus infection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Cell lines with overexpression or knockdown of ZFP36L2 were established using lentiviral vectors carrying genes for overexpression and short-hairpin RNA targeting specific genes, respectively. A plaque assay was employed to determine the viral titer. Immunofluorescence and real-time quantitative polymerase chain reaction were used to measure the viral RNA levels. The in vitro-transcribed RNA transcript derived from a replication-dead Japanese encephalitis virus (JEV) replicon containing the renilla luciferase reporter gene (<jats:italic>J-R2A-NS5mt<\/jats:italic>) was used to assess the stability of the flavivirus RNA. An RNA immunoprecipitation assay was used to detect the protein\u2013RNA binding ability. Confocal microscopic images were captured to analyze protein colocalization.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>ZFP36L2 served as an innate host defender against JEV and dengue virus. ZFP36L2 inhibited flavivirus infection solely through the 5\u2032-3\u2032 XRN1 RNA decay pathway, whereas ZFP36L1 inhibited JEV infection via the 5\u2032-3\u2032 XRN1 and 3\u2032-5\u2032 RNA exosome RNA decay pathways. The direct binding between viral RNA and ZFP36L2 via its CCCH-type zinc finger motifs facilitated the degradation of flavivirus RNA mediated by 5\u2032-3\u2032 XRN1. Furthermore, ZFP36L2 was localized in processing bodies (PBs), which participate in the 5\u2032-3\u2032 XRN1-mediated RNA decay pathway. Nonetheless, the disruption of PBs did not affect the antiviral activity of ZFP36L2, suggesting that its localization is not essential for the function of the protein. Interestingly, the colocalization of ZFP36L2 and XRN1 with viral RNA and NS3 revealed that the antiviral activity of ZFP36L2 occurred within the replication complexes (RCs).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In summary, ZFP36L2 bound to and degraded viral RNA through the XRN1-mediated RNA decay pathway in the RCs, thereby inhibiting flavivirus replication. These findings provide valuable insights into the diverse antiviral mechanisms of the ZFP36-like family of proteins in the innate immune response against flavivirus infection.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12929-025-01122-0","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:01:43Z","timestamp":1740009703000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The zinc finger protein ZFP36L2 inhibits flavivirus infection via the 5\u2032-3\u2032 XRN1-mediated RNA decay pathway in the replication complexes"],"prefix":"10.1186","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4196-946X","authenticated-orcid":false,"given":"Ren-Jye","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Hsiung","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zih-Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Cheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin-Chen","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Len","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"1122_CR1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.cytogfr.2007.06.003","volume":"18","author":"AG Hovanessian","year":"2007","unstructured":"Hovanessian AG. On the discovery of interferon-inducible, double-stranded RNA activated enzymes: the 2\u02b9-5\u02b9oligoadenylate synthetases and the protein kinase PKR. Cytokine Growth Factor Rev. 2007;18:351\u201361.","journal-title":"Cytokine Growth Factor Rev"},{"key":"1122_CR2","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1128\/CMR.14.4.778-809.2001","volume":"14","author":"CE Samuel","year":"2001","unstructured":"Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev. 2001;14:778\u2013809 (table of contents).","journal-title":"Clin Microbiol Rev"},{"key":"1122_CR3","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1126\/science.1074276","volume":"297","author":"G Gao","year":"2002","unstructured":"Gao G, Guo X, Goff SP. Inhibition of retroviral RNA production by ZAP, a CCCH-type zinc finger protein. Science. 2002;297:1703\u20136.","journal-title":"Science"},{"key":"1122_CR4","doi-asserted-by":"publisher","first-page":"12781","DOI":"10.1128\/JVI.78.23.12781-12787.2004","volume":"78","author":"X Guo","year":"2004","unstructured":"Guo X, Carroll JW, Macdonald MR, Goff SP, Gao G. The zinc finger antiviral protein directly binds to specific viral mRNAs through the CCCH zinc finger motifs. J Virol. 2004;78:12781\u20137.","journal-title":"J Virol"},{"key":"1122_CR5","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1073\/pnas.0607063104","volume":"104","author":"X Guo","year":"2007","unstructured":"Guo X, Ma J, Sun J, Gao G. The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA. Proc Natl Acad Sci USA. 2007;104:151\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1122_CR6","doi-asserted-by":"publisher","first-page":"15834","DOI":"10.1073\/pnas.1101676108","volume":"108","author":"Y Zhu","year":"2011","unstructured":"Zhu Y, Chen G, Lv F, Wang X, Ji X, Xu Y, et al. Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation. Proc Natl Acad Sci USA. 2011;108:15834\u20139.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1122_CR7","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.3390\/pathogens12121461","volume":"12","author":"KQ de Andrade","year":"2023","unstructured":"de Andrade KQ, Cirne-Santos CC. Antiviral activity of zinc finger antiviral protein (ZAP) in different virus families. Pathogens. 2023;12:1461.","journal-title":"Pathogens"},{"key":"1122_CR8","doi-asserted-by":"publisher","first-page":"2681","DOI":"10.1073\/pnas.1621508114","volume":"114","author":"T Kozaki","year":"2017","unstructured":"Kozaki T, Komano J, Kanbayashi D, Takahama M, Misawa T, Satoh T, et al. Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response. Proc Natl Acad Sci USA. 2017;114:2681\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1122_CR9","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01665-21","volume":"96","author":"H Chiu","year":"2022","unstructured":"Chiu H, Chiu HP, Yu HP, Lin LH, Chen ZP, Lin YL, et al. Zinc finger protein zfp36l1 inhibits flavivirus infection by both 5\u02b9-3\u02b9 XRN1 and 3\u02b9-5\u02b9 RNA-exosome RNA decay pathways. J Virol. 2022;96: e0166521.","journal-title":"J Virol"},{"key":"1122_CR10","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/wrna.28","volume":"2","author":"S Sanduja","year":"2011","unstructured":"Sanduja S, Blanco FF, Dixon DA. The roles of TTP and BRF proteins in regulated mRNA decay. Wiley Interdiscip Rev RNA. 2011;2:42\u201357.","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"1122_CR11","doi-asserted-by":"publisher","first-page":"10037","DOI":"10.1093\/nar\/gku652","volume":"42","author":"S Adachi","year":"2014","unstructured":"Adachi S, Homoto M, Tanaka R, Hioki Y, Murakami H, Suga H, et al. ZFP36L1 and ZFP36L2 control LDLR mRNA stability via the ERK-RSK pathway. Nucleic Acids Res. 2014;42:10037\u201349.","journal-title":"Nucleic Acids Res"},{"key":"1122_CR12","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/nsmb738","volume":"11","author":"BP Hudson","year":"2004","unstructured":"Hudson BP, Martinez-Yamout MA, Dyson HJ, Wright PE. Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. Nat Struct Mol Biol. 2004;11:257\u201364.","journal-title":"Nat Struct Mol Biol"},{"key":"1122_CR13","doi-asserted-by":"publisher","first-page":"17827","DOI":"10.1074\/jbc.M001696200","volume":"275","author":"WS Lai","year":"2000","unstructured":"Lai WS, Carballo E, Thorn JM, Kennington EA, Blackshear PJ. Interactions of CCCH zinc finger proteins with mRNA. Binding of tristetraprolin-related zinc finger proteins to Au-rich elements and destabilization of mRNA. J Biol Chem. 2000;275:17827\u201337.","journal-title":"J Biol Chem"},{"key":"1122_CR14","doi-asserted-by":"publisher","first-page":"13116","DOI":"10.1074\/jbc.M111.330837","volume":"287","author":"SB Ramos","year":"2012","unstructured":"Ramos SB. Characterization of DeltaN-Zfp36l2 mutant associated with arrest of early embryonic development and female infertility. J Biol Chem. 2012;287:13116\u201327.","journal-title":"J Biol Chem"},{"key":"1122_CR15","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1182\/blood-2009-04-214619","volume":"114","author":"DJ Stumpo","year":"2009","unstructured":"Stumpo DJ, Broxmeyer HE, Ward T, Cooper S, Hangoc G, Chung YJ, et al. Targeted disruption of Zfp36l2, encoding a CCCH tandem zinc finger RNA-binding protein, results in defective hematopoiesis. Blood. 2009;114:2401\u201310.","journal-title":"Blood"},{"key":"1122_CR16","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/ni.1901","volume":"11","author":"DJ Hodson","year":"2010","unstructured":"Hodson DJ, Janas ML, Galloway A, Bell SE, Andrews S, Li CM, et al. Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia. Nat Immunol. 2010;11:717\u201324.","journal-title":"Nat Immunol"},{"key":"1122_CR17","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/s41590-018-0155-6","volume":"19","author":"F Salerno","year":"2018","unstructured":"Salerno F, Engels S, van den Biggelaar M, van Alphen FPJ, Guislain A, Zhao W, et al. Translational repression of pre-formed cytokine-encoding mRNA prevents chronic activation of memory T cells. Nat Immunol. 2018;19:828\u201337.","journal-title":"Nat Immunol"},{"key":"1122_CR18","doi-asserted-by":"publisher","first-page":"2742","DOI":"10.1038\/s41598-018-21160-z","volume":"8","author":"FM Suk","year":"2018","unstructured":"Suk FM, Chang CC, Lin RJ, Lin SY, Liu SC, Jau CF, et al. ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner. Sci Rep. 2018;8:2742.","journal-title":"Sci Rep"},{"key":"1122_CR19","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1126\/science.aad5978","volume":"352","author":"A Galloway","year":"2016","unstructured":"Galloway A, Saveliev A, \u0141ukasiak S, Hodson DJ, Bolland D, Balmanno K, et al. RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence. Science. 2016;352:453\u20139.","journal-title":"Science"},{"key":"1122_CR20","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13395-018-0183-9","volume":"8","author":"AJH Bye","year":"2018","unstructured":"Bye AJH, Pugazhendhi D, Woodhouse S, Brien P, Watson R, Turner M, et al. The RNA-binding proteins Zfp36l1 and Zfp36l2 act redundantly in myogenesis. Skelet Muscle. 2018;8:37.","journal-title":"Skelet Muscle"},{"key":"1122_CR21","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.3390\/cancers12061539","volume":"12","author":"Y Saini","year":"2020","unstructured":"Saini Y, Chen J, Patial S. The tristetraprolin family of RNA-binding proteins in cancer: progress and future prospects. Cancers (Basel). 2020;12:1539.","journal-title":"Cancers (Basel)"},{"key":"1122_CR22","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1038\/s41419-021-03876-5","volume":"12","author":"F Wu","year":"2021","unstructured":"Wu F, Huang W, Tan Q, Guo Y, Cao Y, Shang J, et al. ZFP36L2 regulates myocardial ischemia\/reperfusion injury and attenuates mitochondrial fusion and fission by LncRNA PVT1. Cell Death Dis. 2021;12:614.","journal-title":"Cell Death Dis"},{"key":"1122_CR23","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.jid.2021.06.030","volume":"142","author":"C Angiolilli","year":"2022","unstructured":"Angiolilli C, Leijten EFA, Bekker CPJ, Eeftink E, Giovannone B, Nordkamp MO, et al. ZFP36 family members regulate the proinflammatory features of psoriatic dermal fibroblasts. J Invest Dermatol. 2022;142:402\u201313.","journal-title":"J Invest Dermatol"},{"key":"1122_CR24","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.molcel.2011.09.019","volume":"44","author":"JA Arribere","year":"2011","unstructured":"Arribere JA, Doudna JA, Gilbert WV. Reconsidering movement of eukaryotic mRNAs between polysomes and P bodies. Mol Cell. 2011;44:745\u201358.","journal-title":"Mol Cell"},{"key":"1122_CR25","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1016\/j.molcel.2009.11.020","volume":"36","author":"JR Buchan","year":"2009","unstructured":"Buchan JR, Parker R. Eukaryotic stress granules: the ins and outs of translation. Mol Cell. 2009;36:932\u201341.","journal-title":"Mol Cell"},{"key":"1122_CR26","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.cellsig.2010.08.011","volume":"23","author":"MG Thomas","year":"2011","unstructured":"Thomas MG, Loschi M, Desbats MA, Boccaccio GL. RNA granules: the good, the bad and the ugly. Cell Signal. 2011;23:324\u201334.","journal-title":"Cell Signal"},{"key":"1122_CR27","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1002\/cbin.11527","volume":"45","author":"S Kanakamani","year":"2021","unstructured":"Kanakamani S, Suresh PS, Venkatesh T. Regulation of processing bodies: from viruses to cancer epigenetic machinery. Cell Biol Int. 2021;45:708\u201319.","journal-title":"Cell Biol Int"},{"key":"1122_CR28","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1002\/wrna.1162","volume":"4","author":"RE Lloyd","year":"2013","unstructured":"Lloyd RE. Regulation of stress granules and P-bodies during RNA virus infection. Wiley Interdiscip Rev RNA. 2013;4:317\u201331.","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"1122_CR29","doi-asserted-by":"publisher","first-page":"183","DOI":"10.18388\/abp.2015_1060","volume":"63","author":"M Malinowska","year":"2016","unstructured":"Malinowska M, Nied\u017awiedzka-Rystwej P, Tokarz-Deptu\u0142a B, Deptu\u0142a W. Stress granules (SG) and processing bodies (PB) in viral infections. Acta Biochim Pol. 2016;63:183\u20138.","journal-title":"Acta Biochim Pol"},{"key":"1122_CR30","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.virol.2012.11.017","volume":"436","author":"LC Reineke","year":"2013","unstructured":"Reineke LC, Lloyd RE. Diversion of stress granules and P-bodies during viral infection. Virology. 2013;436:255\u201367.","journal-title":"Virology"},{"key":"1122_CR31","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1021\/acs.biochem.7b01162","volume":"57","author":"Y Luo","year":"2018","unstructured":"Luo Y, Na Z, Slavoff SA. P-Bodies: composition, properties, and functions. Biochemistry. 2018;57:2424\u201331.","journal-title":"Biochemistry"},{"key":"1122_CR32","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.bbagrm.2013.03.005","volume":"1829","author":"VK Nagarajan","year":"2013","unstructured":"Nagarajan VK, Jones CI, Newbury SF, Green PJ. XRN 5\u02b9\u21923\u02b9 exoribonucleases: structure, mechanisms and functions. Biochim Biophys Acta. 2013;1829:590\u2013603.","journal-title":"Biochim Biophys Acta"},{"key":"1122_CR33","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1073\/pnas.1213515110","volume":"110","author":"Y Li","year":"2013","unstructured":"Li Y, Masaki T, Yamane D, McGivern DR, Lemon SM. Competing and noncompeting activities of miR-122 and the 5\u02b9 exonuclease Xrn1 in regulation of hepatitis C virus replication. Proc Natl Acad Sci USA. 2013;110:1881\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1122_CR34","doi-asserted-by":"publisher","first-page":"4857","DOI":"10.1128\/JVI.03692-14","volume":"89","author":"Y Li","year":"2015","unstructured":"Li Y, Yamane D, Lemon SM. Dissecting the roles of the 5\u02b9 exoribonucleases Xrn1 and Xrn2 in restricting hepatitis C virus replication. J Virol. 2015;89:4857\u201365.","journal-title":"J Virol"},{"key":"1122_CR35","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1038\/s41418-020-0509-0","volume":"27","author":"CS Ng","year":"2020","unstructured":"Ng CS, Kasumba DM, Fujita T, Luo H. Spatio-temporal characterization of the antiviral activity of the XRN1-DCP1\/2 aggregation against cytoplasmic RNA viruses to prevent cell death. Cell Death Differ. 2020;27:2363\u201382.","journal-title":"Cell Death Differ"},{"key":"1122_CR36","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/S0966-842X(01)02288-0","volume":"10","author":"DJ Gubler","year":"2002","unstructured":"Gubler DJ. Epidemic dengue\/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol. 2002;10:100\u20133.","journal-title":"Trends Microbiol"},{"key":"1122_CR37","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1080\/13550280390194037","volume":"9","author":"T Solomon","year":"2003","unstructured":"Solomon T. Recent advances in Japanese encephalitis. J Neurovirol. 2003;9:274\u201383.","journal-title":"J Neurovirol"},{"key":"1122_CR38","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/S0042-6822(02)00130-7","volume":"307","author":"PD Uchil","year":"2003","unstructured":"Uchil PD, Satchidanandam V. Characterization of RNA synthesis, replication mechanism, and in vitro RNA-dependent RNA polymerase activity of Japanese encephalitis virus. Virology. 2003;307:358\u201371.","journal-title":"Virology"},{"key":"1122_CR39","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0065-3527(03)59004-2","volume":"59","author":"EG Westaway","year":"2003","unstructured":"Westaway EG, Mackenzie JM, Khromykh AA. Kunjin RNA replication and applications of Kunjin replicons. Adv Virus Res. 2003;59:99\u2013140.","journal-title":"Adv Virus Res"},{"key":"1122_CR40","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1006\/viro.1996.0457","volume":"223","author":"LK Chen","year":"1996","unstructured":"Chen LK, Lin YL, Liao CL, Lin CG, Huang YL, Yeh CT, et al. Generation and characterization of organ-tropism mutants of Japanese encephalitis virus in vivo and in vitro. Virology. 1996;223:79\u201388.","journal-title":"Virology"},{"key":"1122_CR41","doi-asserted-by":"publisher","first-page":"9729","DOI":"10.1128\/JVI.72.12.9729-9737.1998","volume":"72","author":"YL Lin","year":"1998","unstructured":"Lin YL, Liao CL, Chen LK, Yeh CT, Liu CI, Ma SH, et al. Study of dengue virus infection in SCID mice engrafted with human K562 cells. J Virol. 1998;72:9729\u201337.","journal-title":"J Virol"},{"key":"1122_CR42","doi-asserted-by":"publisher","first-page":"8035","DOI":"10.4049\/jimmunol.0902728","volume":"183","author":"RJ Lin","year":"2009","unstructured":"Lin RJ, Yu HP, Chang BL, Tang WC, Liao CL, Lin YL. Distinct antiviral roles for human 2\u02b9,5\u02b9-oligoadenylate synthetase family members against dengue virus infection. J Immunol. 2009;183:8035\u201343.","journal-title":"J Immunol"},{"key":"1122_CR43","doi-asserted-by":"publisher","first-page":"970","DOI":"10.2144\/00295bm08","volume":"29","author":"O Makarova","year":"2000","unstructured":"Makarova O, Kamberov E, Margolis B. Generation of deletion and point mutations with one primer in a single cloning step. Biotechniques. 2000;29:970\u20132.","journal-title":"Biotechniques"},{"key":"1122_CR44","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1006\/viro.1996.0109","volume":"217","author":"LK Chen","year":"1996","unstructured":"Chen LK, Liao CL, Lin CG, Lai SC, Liu CI, Ma SH, et al. Persistence of Japanese encephalitis virus is associated with abnormal expression of the nonstructural protein NS1 in host cells. Virology. 1996;217:220\u20139.","journal-title":"Virology"},{"key":"1122_CR45","doi-asserted-by":"publisher","first-page":"3314","DOI":"10.1093\/nar\/gkt019","volume":"41","author":"RJ Lin","year":"2013","unstructured":"Lin RJ, Chien HL, Lin SY, Chang BL, Yu HP, Tang WC, et al. MCPIP1 ribonuclease exhibits broad-spectrum antiviral effects through viral RNA binding and degradation. Nucleic Acids Res. 2013;41:3314\u201326.","journal-title":"Nucleic Acids Res"},{"key":"1122_CR46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007166","volume":"14","author":"HP Chiu","year":"2018","unstructured":"Chiu HP, Chiu H, Yang CF, Lee YL, Chiu FL, Kuo HC, et al. Inhibition of Japanese encephalitis virus infection by the host zinc-finger antiviral protein. PLoS Pathog. 2018;14: e1007166.","journal-title":"PLoS Pathog"},{"key":"1122_CR47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004750","volume":"11","author":"YT Kao","year":"2015","unstructured":"Kao YT, Chang BL, Liang JJ, Tsai HJ, Lee YL, Lin RJ, et al. Japanese encephalitis virus nonstructural protein NS5 interacts with mitochondrial trifunctional protein and impairs fatty acid \u03b2-oxidation. PLoS Pathog. 2015;11: e1004750.","journal-title":"PLoS Pathog"},{"key":"1122_CR48","doi-asserted-by":"publisher","first-page":"4698","DOI":"10.1128\/JVI.01950-10","volume":"85","author":"HL Chien","year":"2011","unstructured":"Chien HL, Liao CL, Lin YL. FUSE binding protein 1 interacts with untranslated regions of Japanese encephalitis virus RNA and negatively regulates viral replication. J Virol. 2011;85:4698\u2013706.","journal-title":"J Virol"},{"key":"1122_CR49","doi-asserted-by":"publisher","first-page":"9606","DOI":"10.1074\/jbc.M110395200","volume":"277","author":"WS Lai","year":"2002","unstructured":"Lai WS, Kennington EA, Blackshear PJ. Interactions of CCCH zinc finger proteins with mRNA: non-binding tristetraprolin mutants exert an inhibitory effect on degradation of AU-rich element-containing mRNAs. J Biol Chem. 2002;277:9606\u201313.","journal-title":"J Biol Chem"},{"key":"1122_CR50","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1002\/pro.401","volume":"19","author":"BR Morgan","year":"2010","unstructured":"Morgan BR, Massi F. A computational study of RNA binding and specificity in the tandem zinc finger domain of TIS11d. Protein Sci. 2010;19:1222\u201334.","journal-title":"Protein Sci"},{"key":"1122_CR51","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1101\/gad.1282305","volume":"19","author":"J Lykke-Andersen","year":"2005","unstructured":"Lykke-Andersen J, Wagner E. Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1. Genes Dev. 2005;19:351\u201361.","journal-title":"Genes Dev"},{"key":"1122_CR52","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1042\/bst0300963","volume":"30","author":"N Kedersha","year":"2002","unstructured":"Kedersha N, Anderson P. Stress granules: sites of mRNA triage that regulate mRNA stability and translatability. Biochem Soc Trans. 2002;30:963\u20139.","journal-title":"Biochem Soc Trans"},{"key":"1122_CR53","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1038\/sj.emboj.7600163","volume":"23","author":"G Stoecklin","year":"2004","unstructured":"Stoecklin G, Stubbs T, Kedersha N, Wax S, Rigby WF, Blackwell TK, et al. MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay. Embo J. 2004;23:1313\u201324.","journal-title":"Embo J"},{"key":"1122_CR54","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1083\/jcb.200502088","volume":"169","author":"N Kedersha","year":"2005","unstructured":"Kedersha N, Stoecklin G, Ayodele M, Yacono P, Lykke-Andersen J, Fritzler MJ, et al. Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol. 2005;169:871\u201384.","journal-title":"J Cell Biol"},{"key":"1122_CR55","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1101\/gad.1538807","volume":"21","author":"G Stoecklin","year":"2007","unstructured":"Stoecklin G, Anderson P. In a tight spot: ARE-mRNAs at processing bodies. Genes Dev. 2007;21:627\u201331.","journal-title":"Genes Dev"},{"key":"1122_CR56","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1017\/S1355838202021726","volume":"8","author":"D Ingelfinger","year":"2002","unstructured":"Ingelfinger D, Arndt-Jovin DJ, L\u00fchrmann R, Achsel T. The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1\/2 and Xrnl in distinct cytoplasmic foci. RNA. 2002;8:1489\u2013501.","journal-title":"RNA"},{"key":"1122_CR57","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1126\/science.1082320","volume":"300","author":"U Sheth","year":"2003","unstructured":"Sheth U, Parker R. Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science. 2003;300:805\u20138.","journal-title":"Science"},{"key":"1122_CR58","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1261\/rna.2340405","volume":"11","author":"MA Andrei","year":"2005","unstructured":"Andrei MA, Ingelfinger D, Heintzmann R, Achsel T, Rivera-Pomar R, L\u00fchrmann R. A role for eIF4E and eIF4E-transporter in targeting mRNPs to mammalian processing bodies. RNA. 2005;11:717\u201327.","journal-title":"RNA"},{"key":"1122_CR59","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1083\/jcb.200504039","volume":"170","author":"MA Ferraiuolo","year":"2005","unstructured":"Ferraiuolo MA, Basak S, Dostie J, Murray EL, Schoenberg DR, Sonenberg N. A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay. J Cell Biol. 2005;170:913\u201324.","journal-title":"J Cell Biol"},{"key":"1122_CR60","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1111\/j.1600-0854.2005.00339.x","volume":"6","author":"J Mackenzie","year":"2005","unstructured":"Mackenzie J. Wrapping things up about virus RNA replication. Traffic. 2005;6:967\u201377.","journal-title":"Traffic"},{"key":"1122_CR61","first-page":"139","volume":"285","author":"A Salonen","year":"2005","unstructured":"Salonen A, Ahola T, K\u00e4\u00e4ri\u00e4inen L. Viral RNA replication in association with cellular membranes. Curr Top Microbiol Immunol. 2005;285:139\u201373.","journal-title":"Curr Top Microbiol Immunol"},{"key":"1122_CR62","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/nrmicro1890","volume":"6","author":"S Miller","year":"2008","unstructured":"Miller S, Krijnse-Locker J. Modification of intracellular membrane structures for virus replication. Nat Rev Microbiol. 2008;6:363\u201374.","journal-title":"Nat Rev Microbiol"},{"key":"1122_CR63","first-page":"7371","volume":"48","author":"RJ Lin","year":"2020","unstructured":"Lin RJ, Huang CH, Liu PC, Lin IC, Huang YL, Chen AY, et al. Zinc finger protein ZFP36L1 inhibits influenza A virus through translational repression by targeting HA, M and NS RNA transcripts. Nucleic Acids Res. 2020;48:7371\u201384.","journal-title":"Nucleic Acids Res"},{"key":"1122_CR64","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.chom.2008.10.007","volume":"4","author":"GP Pijlman","year":"2008","unstructured":"Pijlman GP, Funk A, Kondratieva N, Leung J, Torres S, van der Aa L, et al. A highly structured, nuclease-resistant, noncoding RNA produced by flaviviruses is required for pathogenicity. Cell Host Microbe. 2008;4:579\u201391.","journal-title":"Cell Host Microbe"},{"key":"1122_CR65","doi-asserted-by":"publisher","first-page":"11395","DOI":"10.1128\/JVI.01047-10","volume":"84","author":"PA Silva","year":"2010","unstructured":"Silva PA, Pereira CF, Dalebout TJ, Spaan WJ, Bredenbeek PJ. An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1. J Virol. 2010;84:11395\u2013406.","journal-title":"J Virol"},{"key":"1122_CR66","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1126\/science.1250897","volume":"344","author":"EG Chapman","year":"2014","unstructured":"Chapman EG, Costantino DA, Rabe JL, Moon SL, Wilusz J, Nix JC, et al. The structural basis of pathogenic subgenomic flavivirus RNA (sfRNA) production. Science. 2014;344:307\u201310.","journal-title":"Science"},{"key":"1122_CR67","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01892","volume":"3","author":"EG Chapman","year":"2014","unstructured":"Chapman EG, Moon SL, Wilusz J, Kieft JS. RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA. Elife. 2014;3: e01892.","journal-title":"Elife"},{"key":"1122_CR68","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41467-017-02604-y","volume":"9","author":"A MacFadden","year":"2018","unstructured":"MacFadden A, O\u2019Donoghue Z, Silva P, Chapman EG, Olsthoorn RC, Sterken MG, et al. Mechanism and structural diversity of exoribonuclease-resistant RNA structures in flaviviral RNAs. Nat Commun. 2018;9:119.","journal-title":"Nat Commun"},{"key":"1122_CR69","doi-asserted-by":"publisher","first-page":"5708","DOI":"10.1128\/JVI.00207-12","volume":"86","author":"A Schuessler","year":"2012","unstructured":"Schuessler A, Funk A, Lazear HM, Cooper DA, Torres S, Daffis S, et al. West Nile virus noncoding subgenomic RNA contributes to viral evasion of the type I interferon-mediated antiviral response. J Virol. 2012;86:5708\u201318.","journal-title":"J Virol"},{"key":"1122_CR70","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.vetmic.2013.04.026","volume":"166","author":"RY Chang","year":"2013","unstructured":"Chang RY, Hsu TW, Chen YL, Liu SF, Tsai YJ, Lin YT, et al. Japanese encephalitis virus non-coding RNA inhibits activation of interferon by blocking nuclear translocation of interferon regulatory factor 3. Vet Microbiol. 2013;166:11\u201321.","journal-title":"Vet Microbiol"},{"key":"1122_CR71","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1126\/science.aab3369","volume":"350","author":"G Manokaran","year":"2015","unstructured":"Manokaran G, Finol E, Wang C, Gunaratne J, Bahl J, Ong EZ, et al. Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness. Science. 2015;350:217\u201321.","journal-title":"Science"},{"key":"1122_CR72","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1261\/rna.034330.112","volume":"18","author":"SL Moon","year":"2012","unstructured":"Moon SL, Anderson JR, Kumagai Y, Wilusz CJ, Akira S, Khromykh AA, et al. A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability. RNA. 2012;18:2029\u201340.","journal-title":"RNA"},{"key":"1122_CR73","doi-asserted-by":"publisher","first-page":"13486","DOI":"10.1128\/JVI.01104-12","volume":"86","author":"E Schnettler","year":"2012","unstructured":"Schnettler E, Sterken MG, Leung JY, Metz SW, Geertsema C, Goldbach RW, et al. Noncoding flavivirus RNA displays RNA interference suppressor activity in insect and mammalian cells. J Virol. 2012;86:13486\u2013500.","journal-title":"J Virol"},{"key":"1122_CR74","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1186\/1743-422X-8-492","volume":"8","author":"YH Fan","year":"2011","unstructured":"Fan YH, Nadar M, Chen CC, Weng CC, Lin YT, Chang RY. Small noncoding RNA modulates Japanese encephalitis virus replication and translation in trans. Virol J. 2011;8:492.","journal-title":"Virol J"},{"key":"1122_CR75","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.chom.2008.03.004","volume":"3","author":"CJ Beckham","year":"2008","unstructured":"Beckham CJ, Parker R. P bodies, stress granules, and viral life cycles. Cell Host Microbe. 2008;3:206\u201312.","journal-title":"Cell Host Microbe"},{"key":"1122_CR76","doi-asserted-by":"publisher","first-page":"9041","DOI":"10.1073\/pnas.0703348104","volume":"104","author":"MM Emara","year":"2007","unstructured":"Emara MM, Brinton MA. Interaction of TIA-1\/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly. Proc Natl Acad Sci USA. 2007;104:9041\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1122_CR77","volume":"2009","author":"M Baou","year":"2009","unstructured":"Baou M, Jewell A, Murphy JJ. TIS11 family proteins and their roles in posttranscriptional gene regulation. J Biomed Biotechnol. 2009;2009: 634520.","journal-title":"J Biomed Biotechnol"},{"key":"1122_CR78","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1002\/(SICI)1096-9071(199702)51:2<132::AID-JMV8>3.0.CO;2-8","volume":"51","author":"V Ravi","year":"1997","unstructured":"Ravi V, Parida S, Desai A, Chandramuki A, Gourie-Devi M, Grau GE. Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid with clinical outcome in Japanese encephalitis patients. J Med Virol. 1997;51:132\u20136.","journal-title":"J Med Virol"},{"key":"1122_CR79","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1099\/vir.0.19652-0","volume":"85","author":"D Talavera","year":"2004","unstructured":"Talavera D, Castillo AM, Dominguez MC, Gutierrez AE, Meza I. IL8 release, tight junction and cytoskeleton dynamic reorganization conducive to permeability increase are induced by dengue virus infection of microvascular endothelial monolayers. J Gen Virol. 2004;85:1801\u201313.","journal-title":"J Gen Virol"},{"key":"1122_CR80","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1086\/423328","volume":"190","author":"PM Winter","year":"2004","unstructured":"Winter PM, Dung NM, Loan HT, Kneen R, Wills B, le Thu T, et al. Proinflammatory cytokines and chemokines in humans with Japanese encephalitis. J Infect Dis. 2004;190:1618\u201326.","journal-title":"J Infect Dis"},{"key":"1122_CR81","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050387","volume":"7","author":"GN Malavige","year":"2012","unstructured":"Malavige GN, Huang LC, Salimi M, Gomes L, Jayaratne SD, Ogg GS. Cellular and cytokine correlates of severe dengue infection. PLoS ONE. 2012;7: e50387.","journal-title":"PLoS ONE"},{"key":"1122_CR82","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.561366","volume":"10","author":"A Singh","year":"2020","unstructured":"Singh A, Bisht P, Bhattacharya S, Guchhait P. Role of platelet cytokines in dengue virus infection. Front Cell Infect Microbiol. 2020;10: 561366.","journal-title":"Front Cell Infect Microbiol"}],"container-title":["Journal of Biomedical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12929-025-01122-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12929-025-01122-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12929-025-01122-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:01:46Z","timestamp":1740009706000},"score":1,"resource":{"primary":{"URL":"https:\/\/jbiomedsci.biomedcentral.com\/articles\/10.1186\/s12929-025-01122-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,20]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1122"],"URL":"https:\/\/doi.org\/10.1186\/s12929-025-01122-0","relation":{},"ISSN":["1423-0127"],"issn-type":[{"value":"1423-0127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,20]]},"assertion":[{"value":"2 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"No potential conflicts of interest were disclosed.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"27"}}