Beilleau Guillaume, Stalder Hanspeter, Almeida Lea, Oliveira Esteves Blandina I, Alves Marco P, Schweizer Matthias
Institute of Virology and Immunology, Länggass-Str. 122, CH-3001 Bern, Switzerland.
Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, CH-3001 Bern, Switzerland.
Viruses. 2024 Dec 11;16(12):1908. doi: 10.3390/v16121908.
Bovine viral diarrhea virus (BVDV), a pestivirus in the family , is a major livestock pathogen. Horizontal transmission leads to acute transient infections via the oronasal route, whereas vertical transmission might lead to the birth of immunotolerant, persistently infected animals. In both cases, BVDV exerts an immunosuppressive effect, predisposing infected animals to secondary infections. E, an immunomodulatory viral protein, is present on the envelope of the virus and is released as a soluble protein. In this form, it is taken up by cells and, with its RNase activity, degrades single- and double-stranded (ds) RNA, thus preventing activation of the host's interferon system. Here, we show that E of the pestiviruses BVDV and Bungowannah virus effectively inhibit dsRNA-induced IFN synthesis in well-differentiated airway epithelial cells cultured at the air-liquid interface. This activity was observed independently of the side of entry, apical or basolateral, of the pseudostratified, polarized cell layer. Virus infection was successful from both surfaces but was inefficient, requiring several days of incubation. Virus release was almost exclusively restricted to the apical side. This confirms that primary, well-differentiated respiratory epithelial cells cultured at the air-liquid interface are an appropriate model to study viral infection and innate immunotolerance in the bovine respiratory tract. Furthermore, evidence is presented that E might contribute to the immunosuppressive effect observed after BVDV infections, especially in persistently infected animals.
牛病毒性腹泻病毒（BVDV）是黄病毒科的一种瘟病毒，是一种主要的家畜病原体。水平传播通过口鼻途径导致急性短暂感染，而垂直传播可能导致免疫耐受的持续性感染动物出生。在这两种情况下，BVDV都发挥免疫抑制作用，使感染动物易发生继发感染。E是一种免疫调节性病毒蛋白，存在于病毒包膜上，并以可溶性蛋白形式释放。以这种形式，它被细胞摄取，并利用其核糖核酸酶活性降解单链和双链（ds）RNA，从而阻止宿主干扰素系统的激活。在此，我们表明瘟病毒BVDV和邦戈万纳病毒的E能有效抑制在气液界面培养的分化良好的气道上皮细胞中dsRNA诱导的IFN合成。这种活性与假复层极化细胞层的顶端或基底外侧的进入侧无关。从两个表面都能成功感染病毒，但效率不高，需要几天的孵育。病毒释放几乎完全局限于顶端侧。这证实了在气液界面培养的原代分化良好的呼吸道上皮细胞是研究牛呼吸道病毒感染和先天免疫耐受的合适模型。此外，有证据表明E可能导致BVDV感染后观察到的免疫抑制作用，特别是在持续性感染动物中。
