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LincRNA‐EPS impairs host antiviral immunity by antagonizing viral RNA–PKR interaction
Author(s) -
Zhu Jingfei,
Chen Shengchuan,
Sun LiQiong,
Liu Siying,
Bai Xue,
Li Dapei,
Zhang Fan,
Qiao Zigang,
Li Liang,
Yao Haiping,
Xia Yu,
Xu Ping,
Jiang Xiaohui,
Chen Zhengrong,
Yan Yongdong,
Ma Feng
Publication year - 2022
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202153937
Subject(s) - protein kinase r , biology , interferon , stat1 , rna , virology , innate immune system , downregulation and upregulation , microbiology and biotechnology , immune system , gene , signal transduction , immunology , genetics , mitogen activated protein kinase kinase , protein kinase c
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‐β, 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.