Human STAT1 Knockout Cell Line-A549

Zika virus (ZIKV) infection can lead to severe neurological disorders, including neonatal microcephaly and Guillain-Barré syndrome. Long noncoding RNAs (lncRNAs) are byproducts of the transcription process and are thought to influence viral infection. Here, researchers identify a set of human lncRNAs that are upregulated upon ZIKV infection and are dependent on type I interferon (IFN) signaling. Overexpression of the lncRNA ZAP-IT1 results in impaired ZIKV infection. Correspondingly, deficiency of ZAP-IT1 results in enhanced ZIKV infection. Knockout of ZAP-IT1 also results in increased infection with dengue virus (DENV), Japanese encephalitis virus (JEV), or vesicular stomatitis virus (VSV). Thus, these data suggest that the host lncRNA ZAP-IT1, induced by type I IFN signaling, exhibits a strong restrictive effect on ZIKV infection, and even DENV, JEV, and VSV infections, which may facilitate the development of antiviral therapies.

Here, the researchers identified putative binding sites for NF-κB and STAT1, implying a potential association between lncRNA and NF-κB or STAT1 (Figure 1A). They hypothesized that ZIKV might induce the expression of these lncRNAs by activating the IFN signaling pathway. To test this hypothesis, A549 cells were treated with IFN-β. The expression of the four lncRNAs was significantly enhanced after IFN-β treatment (Figure 1B). To further confirm this result, the researchers used MAVS knockout, IFNAR1 knockout, or STAT1 knockout A549 cells, which block the production of IFN and the activation of the IFN signaling pathway. Compared with control cells, the enhanced expression of lncRNAs was blocked after knocking out MAVS, IFNAR1, or STAT1 (Figures 1C and E). These results suggest that LAP3-AS1, LINC21762, VAMP1-AS1, and ZAP-IT1 may belong to interferon-stimulated genes (ISGs) and are specifically induced by activation of IFNs and the IFN pathway.

Figure 1. IFN pathway is involved in the induction of lncRNAs. (Huang Y, et al. 2022)