4.7 Article

Transmissible gastroenteritis virus ORF3b up-regulates miR-885-3p to counteract TNF-α production via inhibiting NF-κB pathway

期刊

VETERINARY MICROBIOLOGY
卷 261, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.vetmic.2021.109189

关键词

TGEV-ORF3b; miR-885-3p; Bcl-10; NF-kappa B; TNF-alpha

资金

  1. National Natural Science Foundation of China [31972645]

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The study revealed that TGEV-ORF3b counteracted the effects of NF-κ B pathway and TNF-α by regulating miR-885-3p and Bcl-10.
Transmissible gastroenteritis (TGE) is an acute viral disease and characterized as severe acute inflammation response that leads to diarrhea, vomiting, and high lethality of piglets. Transmissible gastroenteritis virus (TGEV), a member of coronavirus, is the pathogen of TGE. We previously found NF-kappa B pathway was activated and 65 miRNAs were changed in response to inflammation caused by TGEV in cell line porcine intestinal epithelial cells-jejunum 2 (IPEC-J2). Bioinformatics results showed that these altered miRNAs were relevant to inflammation. In this study, the candidate targets of differentially expressed (DE) miRNAs were predicted and analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Based on the results of KEGG analysis, miR-885-3p might participate in regulating activation of NF-kappa B pathway and TNF pathway. To study the function of miR-885-3p, miR-885-3p mimics and inhibitors were artificially synthesized and respectively used for overexpression and silence of miR-885-3p in cells. Our results showed that miR-885-3p inhibited NF-kappa B signaling pathway and tumor necrosis factor-alpha (TNF-alpha) production. B-cell CLL/lymphoma 10 (Bcl-10) was identified as the target of miR-885-3p, and promoted NF-kappa B pathway activation and TNF-alpha production. It was found that TGEV open reading frame 3b (TGEV-ORF3b) suppressed Bcl-10 expression, activation of NF-kappa B pathway, and TNF-alpha production by uniquely up-regulated miR-885-3p expression. Overall, the results indicated that TGEV-ORF3b counteracted NF-kappa B pathway and TNF-alpha via regulating miR-885-3p and Bcl-10.

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