State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.
Arch Virol. 2019 Nov;164(11):2659-2669. doi: 10.1007/s00705-019-04362-2. Epub 2019 Aug 5.
Interferon gamma (IFN-γ) is best known for its ability to regulate host immune responses; however, its direct antiviral activity is less well studied. Transmissible gastroenteritis virus (TGEV) is an economically important swine enteric coronavirus and causes acute diarrhea in piglets. At present, little is known about the function of IFN-γ in the control of TGEV infection. In this study, we demonstrated that IFN-γ inhibited TGEV infection directly in ST cells and intestine epithelial IPEC-J2 cells and that the anti-TGEV activity of IFN-γ was independent of IFN-α/β. Moreover, IFN-γ suppressed TGEV infection in ST cells more efficiently than did IFN-α, and the combination of IFN-γ and IFN-α displayed a synergistic effect against TGEV. Mechanistically, using overexpression and functional knockdown experiments, we demonstrated that porcine interferon regulatory factor 1 (poIRF1) elicited by IFN-γ primarily mediated IFN-γ signaling cascades and the inhibition of TGEV infection by IFN-γ. Importantly, we found that TGEV elevated the expression of poIRF1 and IFN-γ in infected small intestines and peripheral blood mononuclear cells. Thus, IFN-γ plays a crucial role in curtailing enteric coronavirus infection and may serve as an effective prophylactic and/or therapeutic agent against TGEV infection.
干扰素 γ（IFN-γ）最为人所知的是其调节宿主免疫反应的能力；然而，其直接抗病毒活性的研究较少。传染性胃肠炎病毒（TGEV）是一种具有经济重要性的猪肠道冠状病毒，可引起仔猪急性腹泻。目前，对于 IFN-γ在控制 TGEV 感染中的作用知之甚少。在本研究中，我们证明 IFN-γ可直接抑制 ST 细胞和肠上皮 IPEC-J2 细胞中的 TGEV 感染，IFN-γ 的抗 TGEV 活性不依赖于 IFN-α/β。此外，IFN-γ抑制 ST 细胞中 TGEV 感染的效率高于 IFN-α，IFN-γ 和 IFN-α 的联合对 TGEV 表现出协同作用。在机制上，通过过表达和功能敲低实验，我们证明了 IFN-γ 诱导的猪干扰素调节因子 1（poIRF1）主要介导 IFN-γ 信号级联反应和 IFN-γ 对 TGEV 感染的抑制作用。重要的是，我们发现 TGEV 可上调感染小肠和外周血单核细胞中的 poIRF1 和 IFN-γ 的表达。因此，IFN-γ 在抑制肠道冠状病毒感染中起着至关重要的作用，可能是针对 TGEV 感染的有效预防和/或治疗剂。
