Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
Viruses. 2022 Jan 14;14(1):149. doi: 10.3390/v14010149.
Respiratory disease in horses is caused by a multifactorial complex of infectious agents and environmental factors. An important pathogen in horses is equine herpesvirus type 1 (EHV-1). During co-evolution with this ancient alphaherpesvirus, the horse's respiratory tract has developed multiple antiviral barriers. However, these barriers can become compromised by environmental threats. Pollens and mycotoxins enhance mucosal susceptibility to EHV-1 by interrupting cell junctions, allowing the virus to reach its basolateral receptor. Whether bacterial toxins also play a role in this impairment has not been studied yet. Here, we evaluated the role of α-hemolysin (Hla) and adenylate cyclase (ACT), toxins derived from the facultative pathogenic bacterium () and the primary pathogen (), respectively. Equine respiratory mucosal explants were cultured at an air-liquid interface and pretreated with these toxins, prior to EHV-1 inoculation. Morphological analysis of hematoxylin-eosin (HE)-stained sections of the explants revealed a decreased epithelial thickness upon treatment with both toxins. Additionally, the Hla toxin induced detachment of epithelial cells and a partial loss of cilia. These morphological changes were correlated with increased EHV-1 replication in the epithelium, as assessed by immunofluorescent stainings and confocal microscopy. In view of these results, we argue that the ACT and Hla toxins increase the susceptibility of the epithelium to EHV-1 by disrupting the epithelial barrier function. In conclusion, this study is the first to report that bacterial exotoxins increase the horse's sensitivity to EHV-1 infection. Therefore, we propose that horses suffering from infection by or may be more susceptible to EHV-1 infection.
马的呼吸道疾病是由多种传染性病原体和环境因素引起的复杂疾病。马疱疹病毒 1 型（EHV-1）是马的重要病原体之一。在与这种古老的α疱疹病毒共同进化的过程中，马的呼吸道已经发展出多种抗病毒屏障。然而，这些屏障可能会受到环境威胁的影响而受损。花粉和霉菌毒素通过中断细胞连接，使病毒能够到达基底外侧受体，从而增加了马的呼吸道对 EHV-1 的易感性。细菌毒素是否也在这种损害中起作用尚未得到研究。在这里，我们评估了来自兼性致病菌（）和主要病原体（）的α-溶血素（Hla）和腺苷酸环化酶（ACT）毒素的作用。马呼吸道黏膜外植体在气液界面培养，并在接种 EHV-1 之前用这些毒素预处理。用这些毒素处理后，对黏膜外植体的苏木精-伊红（HE）染色切片进行形态分析，发现上皮细胞厚度减少。此外，Hla 毒素诱导上皮细胞脱落和部分纤毛丧失。这些形态变化与上皮细胞中 EHV-1 复制的增加相关，通过免疫荧光染色和共聚焦显微镜评估。鉴于这些结果，我们认为 ACT 和 Hla 毒素通过破坏上皮屏障功能增加了上皮对 EHV-1 的易感性。总之，本研究首次报道了细菌外毒素增加了马对 EHV-1 感染的敏感性。因此，我们提出感染或的马可能更容易感染 EHV-1。
