Single-cell RNA sequencing reveals SARS-CoV-2 infection dynamics in lungs of African green monkeys.
Single-cell RNA sequencing reveals SARS-CoV-2 infection dynamics in lungs of African green monkeys.
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DOI：
10.1126/scitranslmed.abe8146
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发表时间：
2021-01-27
影响因子：
17.1
通讯作者：
de Wit E
中科院分区：
文献类型：
--
作者：
Speranza E;Williamson BN;Feldmann F;Sturdevant GL;Pérez-Pérez L;Meade-White K;Smith BJ;Lovaglio J;Martens C;Munster VJ;Okumura A;Shaia C;Feldmann H;Best SM;de Wit E
对感染SARS-CoV-2的非洲绿猴肺进行单细胞RNA测序，揭示了体内病毒复制和宿主反应动态。虽然已经开发出了许多SARS-CoV-2的动物模型，但非人灵长类动物是最善于概括人类新冠肺炎的动物之一。在这里，Speranza等人。使用单细胞RNA测序证明SARS-CoV-2在非洲绿猴的肺中复制，肺中的免疫细胞群在感染过程中发生变化。测序数据显示，肺泡细胞是病毒在肺内复制的场所，浸润性巨噬细胞负责在感染早期清除感染细胞和细胞碎片。综上所述，这些发现进一步加深了我们对SARS-CoV-2感染动态和体内宿主免疫反应的理解。详细了解严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的动态，对于揭示导致冠状病毒病2019(新冠肺炎)发病的病毒和宿主因素非常重要。东半球非人灵长类总结了轻到中度的新冠肺炎病例，从而成为重要的发病模式。我们比较了接种传染性SARS-CoV-2或辐射灭活病毒的非洲绿猴，以研究病毒在整个呼吸道的复制动力学。接种受辐射病毒的动物的基因组RNA被发现高度稳定，而作为病毒复制指标的亚基因组RNA被发现迅速降解。我们将这些信息与从肺和肺引流纵隔淋巴结分离的细胞的单细胞RNA测序相结合，开发了新的分析方法，以无偏见地靶向宿主对SARS-CoV-2感染的反应中的重要细胞。通过检测病毒基因组的读数，我们能够确定病毒在肺部的复制似乎主要发生在肺泡细胞中，而巨噬细胞驱动炎症反应。在感染早期，单核细胞来源的巨噬细胞被招募到肺部，而不是驻留在组织中的肺泡巨噬细胞，最有可能负责吞噬感染细胞和细胞碎片，在感染清除过程中，它们的角色互换。总而言之，我们的数据集提供了轻度新冠肺炎过程中病毒复制和宿主反应的动态详细视图，是确定治疗靶点的宝贵资源。
Single-cell RNA sequencing of lungs of SARS-CoV-2–infected African green monkeys reveals virus replication and host response dynamics in vivo. While a number of animal models for SARS-CoV-2 have been developed, nonhuman primates are among the best at recapitulating human COVID-19. Here, Speranza et al. used single-cell RNA sequencing to demonstrate that SARS-CoV-2 replicates in the lung of African green monkeys and that immune cell populations in the lung change over the course of infection. Sequencing data revealed that pneumocytes are the site of viral replication in the lung, and infiltrating macrophages are responsible for clearing infected cells and cellular debris early in infection. Together, these findings further our understanding of the dynamics of SARS-CoV-2 infection and host immune responses in vivo. Detailed knowledge about the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is important for uncovering the viral and host factors that contribute to coronavirus disease 2019 (COVID-19) pathogenesis. Old-World nonhuman primates recapitulate mild to moderate cases of COVID-19, thereby serving as important pathogenesis models. We compared African green monkeys inoculated with infectious SARS-CoV-2 or irradiated, inactivated virus to study the dynamics of virus replication throughout the respiratory tract. Genomic RNA from the animals inoculated with the irradiated virus was found to be highly stable, whereas subgenomic RNA, an indicator of viral replication, was found to degrade quickly. We combined this information with single-cell RNA sequencing of cells isolated from the lung and lung-draining mediastinal lymph nodes and developed new analysis methods for unbiased targeting of important cells in the host response to SARS-CoV-2 infection. Through detection of reads to the viral genome, we were able to determine that replication of the virus in the lungs appeared to occur mainly in pneumocytes, whereas macrophages drove the inflammatory response. Monocyte-derived macrophages recruited to the lungs, rather than tissue-resident alveolar macrophages, were most likely to be responsible for phagocytosis of infected cells and cellular debris early in infection, with their roles switching during clearance of infection. Together, our dataset provides a detailed view of the dynamics of virus replication and host responses over the course of mild COVID-19 and serves as a valuable resource to identify therapeutic targets.
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