| First Author | Zhu J | Year | 2022 |
| Journal | EMBO Rep | Volume | 23 |
| Issue | 5 | Pages | e53937 |
| PubMed ID | 35312140 | Mgi Jnum | J:327556 |
| Mgi Id | MGI:7276059 | Doi | 10.15252/embr.202153937 |
| Citation | Zhu J, et al. (2022) LincRNA-EPS impairs host antiviral immunity by antagonizing viral RNA-PKR interaction. EMBO Rep 23(5):e53937 |
| abstractText | LincRNA-EPS is an important regulator in inflammation. However, the role of lincRNA-EPS in the host response against viral infection is unexplored. Here, we show that lincRNA-EPS is downregulated in macrophages infected with different viruses including VSV, SeV, and HSV-1. Overexpression of lincRNA-EPS facilitates viral infection, while deficiency of lincRNA-EPS protects the host against viral infection in vitro and in vivo. LincRNA-EPS(-/-) macrophages show elevated expression of antiviral interferon-stimulated genes (ISGs) such as Mx1, Oas2, and Ifit2 at both basal and inducible levels. However, IFN-beta, the key upstream inducer of these ISGs, is downregulated in lincRNA-EPS(-/-) macrophages compared with control cells. RNA pulldown and mass spectrometry results indicate that lincRNA-EPS binds to PKR and antagonizes the viral RNA-PKR interaction. PKR activates STAT1 and induces antiviral ISGs independent of IFN-I induction. LincRNA-EPS inhibits PKR-STAT1-ISGs signaling and thus facilitates viral infection. Our study outlines an alternative antiviral pathway, with downregulation of lincRNA-EPS promoting the induction of PKR-STAT1-dependent ISGs, and reveals a potential therapeutic target for viral infectious diseases. |
