Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, 17493 Greifswald-Insel Riems, Germany.
Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, 17493 Greifswald-Insel Riems, Germany.
Viruses. 2023 Apr 13;15(4):961. doi: 10.3390/v15040961.
Respiratory tract epithelium infection plays a primary role in Nipah virus (NiV) pathogenesis and transmission. Knowledge about infection dynamics and host responses to NiV infection in respiratory tract epithelia is scarce. Studies in non-differentiated primary respiratory tract cells or cell lines indicate insufficient interferon (IFN) responses. However, studies are lacking in the determination of complex host response patterns in differentiated respiratory tract epithelia for the understanding of NiV replication and spread in swine. Here we characterized infection and spread of NiV in differentiated primary porcine bronchial epithelial cells (PBEC) cultivated at the air-liquid interface (ALI). After the initial infection of only a few apical cells, lateral spread for 12 days with epithelium disruption was observed without releasing substantial amounts of infectious virus from the apical or basal sides. Deep time course proteomics revealed pronounced upregulation of genes related to type I/II IFN, immunoproteasomal subunits, transporter associated with antigen processing (TAP)-mediated peptide transport, and major histocompatibility complex (MHC) I antigen presentation. Spliceosomal factors were downregulated. We propose a model in which NiV replication in PBEC is slowed by a potent and broad type I/II IFN host response with conversion from 26S proteasomes to immunoproteasomal antigen processing and improved MHC I presentation for adaptive immunity priming. NiV induced cytopathic effects could reflect the focal release of cell-associated NiV, which may contribute to efficient airborne viral spread between pigs.
呼吸道上皮感染在尼帕病毒（NiV）发病机制和传播中起着主要作用。关于呼吸道上皮感染的病毒动力学和宿主反应的知识还很匮乏。在未分化的原代呼吸道细胞或细胞系中的研究表明干扰素（IFN）反应不足。然而，缺乏对分化的呼吸道上皮中复杂宿主反应模式的研究，无法了解 NiV 在猪体内的复制和传播。在这里，我们研究了 NiV 在原代猪支气管上皮细胞（PBEC）中的感染和扩散，这些细胞在气液界面（ALI）培养。在最初只有少数顶端细胞被感染后，观察到 12 天的侧向扩散，导致上皮破裂，但从顶端或基底侧释放出大量的感染性病毒。深度时间进程蛋白质组学揭示了与 I 型/II 型 IFN、免疫蛋白酶体亚基、与抗原处理相关的转运体（TAP）介导的肽转运以及主要组织相容性复合体（MHC）I 抗原呈递相关的基因明显上调。剪接体因子下调。我们提出了一个模型，即在 PBEC 中 NiV 的复制受到强大而广泛的 I 型/II 型 IFN 宿主反应的抑制，该反应导致 26S 蛋白酶体转化为免疫蛋白酶体抗原处理，并改善了 MHC I 呈递，以促进适应性免疫的启动。NiV 诱导的细胞病变效应可能反映了细胞相关 NiV 的局部分泌，这可能有助于猪之间空气传播的病毒有效传播。
