PRJNA658976: SARS-CoV-2 infection dynamics in lungs of African green monkeys
概要: Detailed knowledge about dynamics of SARS-CoV-2 infection in vivo is important for unraveling the viral and host response factors that contribute to COVID-19 pathogenesis. The unknown dose and exposure timing in human infections makes the needed well-controlled time course studies impossible and thus animal models of disease are essential to fill in the gaps in our understanding of disease progression. Old-World nonhuman primate species recapitulate mild COVID-19 cases, thereby serving as important models for studying disease pathogenesis. In this study, we compare African green monkeys (AGM; Chlorocebus sabaeus) inoculated with SARS-CoV-2 to AGM inoculated with a gamma-irradiated form of the virus to study the dynamics of virus replication throughout the respiratory tract and other target tissues. RNA sequencing of single cells from the lungs and mediastinal lymph nodes allowed a high-resolution, simultaneous analysis of virus replication and the host response in these tissues over time. Viral replication was mainly localized to the lower respiratory tract, especially the pneumocyte population. However, even in the absence of active replication, viral genomic RNA is was highly stable, especially in the upper respiratory tract. Macrophages play a vital and dynamic role in initiating a pro-inflammatory state in the lungs, while also interacting with infected pneumocytes. Together, our dataset provides a detailed view of changes in host and virus replication dynamics over the course of a mild COVID-19 infection and serves as a valuable resource to identify new therapeutic targets
项目整体设计: 10 african green monkeys, 2 inoculated with irradiated SARS-CoV-2, 8 with active SARS-CoV-2, single cell sequencing
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Samples were extracted and process directly from African Green Monkeys during necropsy |
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8 animals received active SARS-CoV-2 and 2 received irradiated SARS-CoV-2 |
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Tissues were manually disaccociated, digested with liberase, filtered, and treated with ACK lysis before being processed on the 10X genomics NextGEM instrument |
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Libraries were prepped according to the 10X genomics V3.0 library prep kits |
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Poly(A)+ RNA |
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PAIRED |
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ILLUMINA |
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Illumina NextSeq 550 |
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Single-cell RNA sequencing reveals SARS-CoV-2 infection dynamics in lungs of African green monkeys.
Science translational medicine . 2021-01-11 [PMID:
33431511]
