Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Nat Commun. 2021 Dec 7;12(1):7092. doi: 10.1038/s41467-021-27318-0.
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 apply single-cell RNA sequencing and proteomics to a primary cell model of human nasal epithelium differentiated at air-liquid interface. SARS-CoV-2 demonstrates widespread tropism for nasal epithelial cell types. The host response is dominated by type I and III IFNs and interferon-stimulated gene products. This response is notably delayed in onset relative to viral gene expression and compared to other respiratory viruses. Nevertheless, once established, the paracrine IFN response begins to impact on SARS-CoV-2 replication. When provided prior to infection, recombinant IFNβ or IFNλ1 induces an efficient antiviral state that potently restricts SARS-CoV-2 viral replication, preserving epithelial barrier integrity. These data imply 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.
鼻腔上皮是 SARS-CoV-2 的一个合理进入点，是发病和传播的部位，可能引发宿主对 SARS-CoV-2 的反应。抗病毒干扰素（IFN）反应对于 SARS-CoV-2 的结果至关重要。然而，人们对该组织中 SARS-CoV-2 与先天免疫之间的相互作用知之甚少。在这里，我们应用单细胞 RNA 测序和蛋白质组学技术，对在气液界面分化的人鼻腔上皮原代细胞模型进行研究。SARS-CoV-2 对鼻腔上皮细胞类型表现出广泛的嗜性。宿主反应以 I 型和 III 型 IFN 以及干扰素刺激基因产物为主。与其他呼吸道病毒相比，这种反应在病毒基因表达方面明显延迟。然而，一旦建立，旁分泌 IFN 反应开始对 SARS-CoV-2 的复制产生影响。在感染前给予重组 IFNβ 或 IFNλ1 会诱导有效的抗病毒状态，强烈限制 SARS-CoV-2 病毒的复制，保持上皮屏障的完整性。这些数据表明，SARS-CoV-2 引发的 IFN-I/III 反应始于鼻腔气道，并表明鼻腔内给予重组 IFN 可能是一种潜在的化学预防策略。
