A novel IFNbeta-induced long non-coding RNA ZAP-IT1 interrupts Zika virus replication in A549 cells.

Zika virus (ZIKV) infection can cause severe neurological diseases including neonatal microcephaly and Guillain-Barre syndrome. Long noncoding RNAs (lncRNAs) are the by-products of the transcription process, which are considered to affect viral infection. However, it remains largely unexplored whether host lncRNAs play a role in ZIKV infection. Here, we identified a group of human lncRNAs that were up-regulated upon ZIKV infection and were dependent on the type I interferon (IFN) signaling. Overexpression of lncRNA ZAP-IT1 leads to an impairment of ZIKV infection. Correspondently, deficiency of ZAP-IT1 led to an enhancement of ZIKV infection. We further confirmed that ZAP-IT1, an intronic lncRNA with total 551 ​nt in length, is mainly located in the nuclear upon ZIKV infection. Knockout of ZAP-IT1 also led to the increase of dengue virus (DENV), Japanese encephalitis virus (JEV), or vesicular stomatitis virus (VSV) infection. Mechanically, we found that the antiviral effect of ZAP-IT1 was independent of the type I IFN signaling pathway. Therefore, our data unveiled that host lncRNA ZAP-IT1 induced by the type I IFN signaling, showed robust restriction on ZIKV infection, and even on DENV, JEV, and VSV infection, which may benefit the development of antiviral therapeutics.