The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we applied single-cell RNA sequencing and proteomics to a primary cell model of human nasal epithelium differentiated at air-liquid interface. SARS-CoV-2 demonstrated widespread tropism for nasal epithelial cell types. The host response was dominated by type I and III IFNs and interferon-stimulated gene products. This response was notably delayed in onset relative to viral gene expression and compared to other respiratory viruses. Nevertheless, once established, the paracrine IFN response began to impact on SARS-CoV-2 replication. When provided prior to infection, recombinant IFNβ or IFNλ1 induced an efficient antiviral state that potently restricted SARS-CoV-2 viral replication, preserving epithelial barrier integrity. These data suggest that the IFN-I/III response to SARS-CoV-2 initiates in the nasal airway and suggest nasal delivery of recombinant IFNs to be a potential chemoprophylactic strategy.

中文翻译：

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延迟诱导 I 型和 III 型干扰素介导鼻上皮细胞对 SARS-CoV-2 的耐受性

鼻上皮是 SARS-CoV-2 的一个可能的切入点，它是发病和传播的部位，并可能引发宿主对 SARS-CoV-2 的反应。抗病毒干扰素 (IFN) 反应对 SARS-CoV-2 的结果至关重要。然而，人们对 SARS-CoV-2 与该组织中的先天免疫之间的相互作用知之甚少。在这里，我们将单细胞 RNA 测序和蛋白质组学应用于在气液界面分化的人鼻上皮的原代细胞模型。SARS-CoV-2 对鼻上皮细胞类型表现出广泛的趋向性。宿主反应主要是 I 型和 III 型干扰素和干扰素刺激的基因产物。相对于病毒基因表达以及与其他呼吸道病毒相比，这种反应的发生明显延迟。然而，一旦成立，旁分泌 IFN 反应开始影响 SARS-CoV-2 的复制。在感染前提供重组 IFNβ 或 IFNλ1 可诱导有效的抗病毒状态，有效限制 SARS-CoV-2 病毒复制，保持上皮屏障完整性。这些数据表明，对 SARS-CoV-2 的 IFN-I/III 反应始于鼻气道，并表明重组 IFN 的鼻腔给药是一种潜在的化学预防策略。