Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection
Abstract Background Neurological complications are common in patients affected by COVID-19 due to the ability of SARS-CoV-2 to infect brains. While the mechanisms of this process are not fully understood, it has been proposed that SARS-CoV-2 can infect the cells of the neurovascular unit (NVU), whic...
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| Format: | Article |
| Language: | English |
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BMC
2021-07-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-021-02210-2 |
| _version_ | 1818358927428943872 |
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| author | Silvia Torices Rosalba Cabrera Michael Stangis Oandy Naranjo Nikolai Fattakhov Timea Teglas Daniel Adesse Michal Toborek |
| author_facet | Silvia Torices Rosalba Cabrera Michael Stangis Oandy Naranjo Nikolai Fattakhov Timea Teglas Daniel Adesse Michal Toborek |
| author_sort | Silvia Torices |
| collection | DOAJ |
| description | Abstract Background Neurological complications are common in patients affected by COVID-19 due to the ability of SARS-CoV-2 to infect brains. While the mechanisms of this process are not fully understood, it has been proposed that SARS-CoV-2 can infect the cells of the neurovascular unit (NVU), which form the blood-brain barrier (BBB). The aim of the current study was to analyze the expression pattern of the main SARS-CoV-2 receptors in naïve and HIV-1-infected cells of the NVU in order to elucidate a possible pathway of the virus entry into the brain and a potential modulatory impact of HIV-1 in this process. Methods The gene and protein expression profile of ACE2, TMPRSS2, ADAM17, BSG, DPP4, AGTR2, ANPEP, cathepsin B, and cathepsin L was assessed by qPCR, immunoblotting, and immunostaining, respectively. In addition, we investigated if brain endothelial cells can be affected by the exposure to the S1 subunit of the S protein, the domain responsible for the direct binding of SARS-CoV-2 to the ACE2 receptors. Results The receptors involved in SARS-CoV-2 infection are co-expressed in the cells of the NVU, especially in astrocytes and microglial cells. These receptors are functionally active as exposure of endothelial cells to the SARS CoV-2 S1 protein subunit altered the expression pattern of tight junction proteins, such as claudin-5 and ZO-1. Additionally, HIV-1 infection upregulated ACE2 and TMPRSS2 expression in brain astrocytes and microglia cells. Conclusions These findings provide key insight into SARS-CoV-2 recognition by cells of the NVU and may help to develop possible treatment of CNS complications of COVID-19. |
| first_indexed | 2024-12-13T20:36:47Z |
| format | Article |
| id | doaj.art-03e20f5f5bf546eb8ba5d8aac9a127d7 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-13T20:36:47Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-03e20f5f5bf546eb8ba5d8aac9a127d72022-12-21T23:32:15ZengBMCJournal of Neuroinflammation1742-20942021-07-0118111610.1186/s12974-021-02210-2Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infectionSilvia Torices0Rosalba Cabrera1Michael Stangis2Oandy Naranjo3Nikolai Fattakhov4Timea Teglas5Daniel Adesse6Michal Toborek7Department of Biochemistry and Molecular Biology, University of Miami Miller School of MedicineDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of MedicineDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of MedicineDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of MedicineDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of MedicineDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of MedicineLaboratory of Structural Biology, Instituto Oswaldo Cruz, FiocruzDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of MedicineAbstract Background Neurological complications are common in patients affected by COVID-19 due to the ability of SARS-CoV-2 to infect brains. While the mechanisms of this process are not fully understood, it has been proposed that SARS-CoV-2 can infect the cells of the neurovascular unit (NVU), which form the blood-brain barrier (BBB). The aim of the current study was to analyze the expression pattern of the main SARS-CoV-2 receptors in naïve and HIV-1-infected cells of the NVU in order to elucidate a possible pathway of the virus entry into the brain and a potential modulatory impact of HIV-1 in this process. Methods The gene and protein expression profile of ACE2, TMPRSS2, ADAM17, BSG, DPP4, AGTR2, ANPEP, cathepsin B, and cathepsin L was assessed by qPCR, immunoblotting, and immunostaining, respectively. In addition, we investigated if brain endothelial cells can be affected by the exposure to the S1 subunit of the S protein, the domain responsible for the direct binding of SARS-CoV-2 to the ACE2 receptors. Results The receptors involved in SARS-CoV-2 infection are co-expressed in the cells of the NVU, especially in astrocytes and microglial cells. These receptors are functionally active as exposure of endothelial cells to the SARS CoV-2 S1 protein subunit altered the expression pattern of tight junction proteins, such as claudin-5 and ZO-1. Additionally, HIV-1 infection upregulated ACE2 and TMPRSS2 expression in brain astrocytes and microglia cells. Conclusions These findings provide key insight into SARS-CoV-2 recognition by cells of the NVU and may help to develop possible treatment of CNS complications of COVID-19.https://doi.org/10.1186/s12974-021-02210-2SARS-CoV-2Blood-brain barrierHIV-1ACE2TMPRSS2 |
| spellingShingle | Silvia Torices Rosalba Cabrera Michael Stangis Oandy Naranjo Nikolai Fattakhov Timea Teglas Daniel Adesse Michal Toborek Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection Journal of Neuroinflammation SARS-CoV-2 Blood-brain barrier HIV-1 ACE2 TMPRSS2 |
| title | Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection |
| title_full | Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection |
| title_fullStr | Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection |
| title_full_unstemmed | Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection |
| title_short | Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection |
| title_sort | expression of sars cov 2 related receptors in cells of the neurovascular unit implications for hiv 1 infection |
| topic | SARS-CoV-2 Blood-brain barrier HIV-1 ACE2 TMPRSS2 |
| url | https://doi.org/10.1186/s12974-021-02210-2 |
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