Different Mechanisms Are Utilized by Coronavirus Transmissible Gastroenteritis Virus To Regulate Interferon Lambda 1 and Interferon Lambda 3 Production

文献类型： 外文期刊

第一作者： Xue, Mei

作者： Xue, Mei;Wang, Wenzhe;He, Haojie;Li, Liang;Zhang, Xin;Shi, Hongyan;Liu, Pinghuang;Feng, Li

作者机构：

关键词： coronavirus; type III IFN; RLR-mediated signaling; protein kinase R-like ER kinase; transmissible gastroenteritis virus; nonstructural protein 1 (nsp1); NF-kappa B

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：6.549； 五年影响因子：5.78 ）

ISSN： 0022-538X

年卷期： 2022 年 96 卷 24 期

页码：

收录情况： SCI

摘要： Type III interferons (IFN-lambda) are shown to be preferentially produced by epithelial cells, which provide front-line protection at barrier surfaces. Transmissible gastroenteritis virus (TGEV), belonging to the genus Alphacoronavirus of the family Coronaviridae, can cause severe intestinal injuries in porcine, resulting in enormous economic losses for the swine industry, worldwide. Here, we demonstrated that although IFN-lambda 1 had a higher basal expression, TGEV infection induced more intense IFN-lambda 3 production in vitro and in vivo than did IFN-lambda 1. We explored the underlying mechanism of IFN-lambda induction by TGEV and found a distinct regulation mechanism of IFN-lambda 1 and IFN-lambda 3. The classical RIG-I-like receptor (RLR) pathway is involved in IFN-lambda 3 but not IFN-lambda 1 production. Except for the signaling pathways mediated by RIG-I and MDA5, TGEV nsp1 induces IFN-lambda 1 and IFN-lambda 3 by activating NF-kappa B via the unfolded protein responses (UPR) PERK-eIF2 alpha pathway. Furthermore, functional domain analysis indicated that the induction of IFN-lambda by the TGEV nsp1 protein was located at amino acids 85 to 102 and was dependent on the phosphorylation of eIF2 alpha and the nuclear translocation of NF-kappa B. Moreover, the recombinant TGEV with the altered amino acid motif of nsp1 85-102 was constructed, and the nsp1 (85-102sg) mutant virus significantly reduced the production of IFN-lambda, compared with the wild strain. Compared to the antiviral activities of IFN-lambda 1, the administration of IFN-lambda 3 showed greater antiviral activity against TGEV infections in IPEC-J2 cells. In summary, our data point to the significant role of IFN-lambda in the host innate antiviral responses to coronavirus infections within mucosal organs and in the distinct mechanisms of IFN-lambda 1 and IFN-lambda 3 regulation.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序