Saheb Sharif-Askari, N;
Saheb Sharif-Askari, F;
Mdkhana, B;
Al Heialy, S;
Alsafar, HS;
Hamoudi, R;
Hamid, Q;
(2021)
Enhanced expression of immune checkpoint receptors during SARS-CoV-2 viral infection.
Molecular Therapy & Methods and Clinical Development
, 20
pp. 109-121.
10.1016/j.omtm.2020.11.002.
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Abstract
The immune system is tightly regulated by the activity of stimulatory and inhibitory immune receptors. This immune homeostasis is usually disturbed during chronic viral infection. Using publicly available transcriptomic datasets, we conducted in silico analyses to evaluate the expression pattern of 38 selected immune inhibitory receptors (IRs) associated with different myeloid and lymphoid immune cells during coronavirus disease 2019 (COVID-19) infection. Our analyses revealed a pattern of overall upregulation of IR mRNA during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A large number of IRs expressed on both lymphoid and myeloid cells were upregulated in nasopharyngeal swabs (NPSs), while lymphoid-associated IRs were specifically upregulated in autopsies, reflecting severe, terminal stage COVID-19 disease. Eight genes (BTLA, LAG3, FCGR2B, PDCD1, CEACAM1, CTLA4, CD72, and SIGLEC7), shared by NPSs and autopsies, were more expressed in autopsies and were directly correlated with viral levels. Single-cell data from blood and bronchoalveolar samples also reflected the observed association between IR upregulation and disease severity. Moreover, compared to SARS-CoV-1, influenza, and respiratory syncytial virus infections, the number and intensities of upregulated IRs were higher in SARS-CoV-2 infections. In conclusion, the immunopathology and severity of COVID-19 could be attributed to dysregulation of different immune inhibitors. Targeting one or more of these immune inhibitors could represent an effective therapeutic approach for the treatment of COVID-19 early and late immune dysregulations.
| Type: | Article |
|---|---|
| Title: | Enhanced expression of immune checkpoint receptors during SARS-CoV-2 viral infection |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.omtm.2020.11.002 |
| Publisher version: | https://doi.org/10.1016/j.omtm.2020.11.002 |
| Language: | English |
| Additional information: | © 2020 The Authors. Published under a Creative Commons license (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
| Keywords: | SARS-CoV-2; COVID-19; immune inhibitory receptors; immune checkpoint inhibitors; CEACAM1; SIGLEC10; sialic acid; lung autopsies; respiratory viral infection; influenza A virus |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10148995 |
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