Open AccessPositive Feedback Loop of Long Noncoding RNA OASL-IT1 and Innate Immune Response Restricts the Replication of Zika Virus in Epithelial A549 Cells
Author(s) -
Wang Yi,
Huo Zhiting,
Lin Quanshi,
Lin Yuxia,
Chen Cancan,
Huang Yanxia,
Huang Changbai,
Zhang Junsong,
He Junfang,
Liu Chao,
Zhang Ping
Publication year - 2021
Publication title -
journal of innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.078
H-Index - 64
eISSN - 1662-8128
pISSN - 1662-811X
DOI - 10.1159/000513606
Subject(s) - research article
Expression of host noncoding RNAs and coding mRNAs is significantly altered by viral infection. In the current study, we screened the transcriptional profile of human lung epithelial A549 cells infected with Zika virus (ZIKV) by microarray assay. Seventy-nine long noncoding RNAs (lncRNAs) and 140 mRNAs were differentially expressed (DE). The bioinformatics analysis revealed that the mRNAs adjacent to the DE lncRNAs were closely related to the host responses to viral infection. We selected 7 lncRNAs from the top 50 hits for validation. The quantitative real-time PCR data confirmed that expression of selected lncRNAs was induced by ZIKV infection. Moreover, the expression of 7 lncRNAs was induced by infection of dengue virus, Japanese encephalitis virus, or vesicular stomatitis virus, or by treatment of poly(I:C) and IFN-β. Furthermore, loss of innate immune adaptor IPS-1 or receptor IFNAR1 resulted in lower induction levels of several lncRNAs by ZIKV. Overexpression of 3 lncRNAs (RPL27-OT1, OASL-IT1, and REC8-OT3) reduced the virus yields of ZIKV. Knockout of OASL-IT1 significantly enhanced ZIKV replication. In OASL-IT1 knockout cells, the levels of interferons (IFNs) and the activation of 3 innate immune signaling pathways triggered by ZIKV were dramatically reduced. Collectively, our work found a positive feedback loop in the IFN system, in which IFNs and OASL-IT1 regulate each other, thereby promoting establishment of antiviral defense.