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SARS-CoV-2-associated T-cell infiltration in the central nervous system

ABSTRACT: SARS-CoV-2-associated T-cell infiltration in the central nervous system

PROVIDER: PRJEB67800 | ENA |

REPOSITORIES: ENA

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Single-cell sequencing of glioblastoma reveals central nervous system susceptibility to SARS-CoV-2

Project description:Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the recent global COVID-19 outbreak, which led to a public health emergency. Entry of SARS-CoV-2 into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2) receptor, and cathepsin. Cathepsin degrades the spike protein (S protein), which results in the entry of viral nucleic acid into the human host cell. Methods: We explored the susceptibility of the central nervous system (CNS) to SARS-CoV-2 infection using single-cell transcriptome analysis of glioblastoma. Results: The results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs). Cathepsin B (Cat B) and cathepsin (Cat L) were also strongly expressed in various cell clusters within the glioblastoma microenvironment. Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs and NPCs, from clinical specimens. Conclusions: These findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2-infected patients with neural symptoms, especially those who suffered a glioma.

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Single-cell sequencing of glioblastoma reveals central nervous system susceptibility to SARS-CoV-2

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Project description:SARS-CoV-2 Invades the Central Nervous System via the Olfactory Route in Rhesus Monkeys

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SARS-CoV-2 Invades the Central Nervous System via the Olfactory Route in Rhesus Monkeys

Project description:Purpose: Neurological manifestations are frequently reported in the Coronavirus Disease 2019 (COVID-19) patients. However, the neuroinvasion mechanism of SARS-CoV-2 remains to be determined. In this study, we explored the neuroinvasion of SARS-CoV-2 via our established non-human primate (NHP) model of COVID-19. Single-cell sequencing was conducted to comprehensively determine effects of SARS-CoV-2 infection on the CNS in consideration of the its cellular heterogeneity. Methods: Rhesus monkeys (3-5 kg, 3-5years old) were used for this study. One monkey were intranasally infected with 1x 10^7 PFU of SARS-CoV-2 in 1mL of PBS, and another monkey was intracranially injected with 1x10^6 of SARS-CoV-2 in 200 µl of PBS. One monkey was intranasally and intracranially treated with PBS as a control. We analyzed the tissues collected on the 4 dpi and 7dpi following intranasal inoculation and on the 9 dpi following intracranial inoculation. Two thousand cells were used to create 5 different clusters, including microglia, mature neurons, oligodendrocytes, endothelial vascular cells, and astrocytes. Single-cell sequencing of were sequenced by an Illumina Novaseq6000 sequencer, the sequencing depth of each cell was at least 100,000 reads, and the paired-end 150 bp (PE150) reading strategy was adopted. Results and Conclusions: Single-cell sequencing data showed that mitochondrial-related genes ND3, ATP6 and COX3 were down-regulated in mature neurons, oligodendrocytes, endothelial vascular cells and microglia in the hippocampus, primary olfactory cortex, and cerebral cortex infected with SARS-CoV-2.

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