title: Japanese encephalitis virus non-coding RNA inhibits activation of interferon by blocking nuclear translocation of interferon regulatory factor 3.
abstract: Noncoding RNA (ncRNA) plays a critical role in modulating a broad range of diseases. All arthropod-borne flaviviruses produce short fragment ncRNA (sfRNA) collinear with highly conserved regions of the 3'-untranslated region (UTR) in the viral genome. We show that the molar ratio of sfRNA to genomic RNA in Japanese encephalitis virus (JEV) persistently infected cells is greater than that in acutely infected cells, indicating an sfRNA role in establishing persistent infection. Transfecting excess quantities of sfRNA into JEV-infected cells reduced interferon-β (IFN-β) promoter activity by 57% and IFN-β mRNA levels by 52%, compared to mock-transfected cells. Transfection of sfRNA into JEV-infected cells also reduced phosphorylation of interferon regulatory factor-3 (IRF-3), the IFN-β upstream regulator, and blocked roughly 30% of IRF-3 nuclear localization. Furthermore, JEV-infected sfRNA transfected cells produced 23% less IFN-β-stimulated apoptosis than mock-transfected groups did. Taken together, these results suggest that sfRNA plays a role against host-cell antiviral responses, prevents cells from undergoing apoptosis, and thus contributes to viral persistence.
authors.affiliation: Institute of Biotechnology and Department of Life Science, National Dong Hwa University, Hualien, Taiwan, ROC. rchang@mail.ndhu.edu.tw
authors.forename: Ruey-Yi
authors.initials: RY
authors.lastname: Chang
authors.forename: Ta-Wen
authors.initials: TW
authors.lastname: Hsu
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Chen
authors.forename: Shu-Fan
authors.initials: SF
authors.lastname: Liu
authors.forename: Yi-Jer
authors.initials: YJ
authors.lastname: Tsai
authors.forename: Yun-Tong
authors.initials: YT
authors.lastname: Lin
authors.forename: Yi-Shiuan
authors.initials: YS
authors.lastname: Chen
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Fan
mesh_terms: D020413:3' Untranslated Regions; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004664:Encephalitis Virus, Japanese / Q000235:genetics* / Q000502:physiology; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D022661:RNA, Untranslated; D012367:RNA, Viral; D016899:Interferon-beta
keywords: 3′-UTR; IRF-3; JEV; Persistent infection; ncRNA; sfRNA