A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection?
Following influenza infection, rs2248374-G ERAP2 expressing cells may transcribe an alternative spliced isoform: ERAP2/Iso3. This variant, unlike ERAP2-wt, is unable to trim peptides to be loaded on MHC class I molecules, but it can still dimerize with both ERAP2-wt and ERAP1-wt, thus contributing t...
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MDPI AG
2020-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/9/1951 |
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| author | Irma Saulle Claudia Vanetti Sara Goglia Chiara Vicentini Enrico Tombetti Micaela Garziano Mario Clerici Mara Biasin |
| author_facet | Irma Saulle Claudia Vanetti Sara Goglia Chiara Vicentini Enrico Tombetti Micaela Garziano Mario Clerici Mara Biasin |
| author_sort | Irma Saulle |
| collection | DOAJ |
| description | Following influenza infection, rs2248374-G ERAP2 expressing cells may transcribe an alternative spliced isoform: ERAP2/Iso3. This variant, unlike ERAP2-wt, is unable to trim peptides to be loaded on MHC class I molecules, but it can still dimerize with both ERAP2-wt and ERAP1-wt, thus contributing to profiling an alternative cellular immune-peptidome. In order to verify if the expression of ERAP2/Iso3 may be induced by other pathogens, PBMCs and MDMs isolated from 20 healthy subjects were stimulated with flu, LPS, CMV, HIV-AT-2, SARS-CoV-2 antigens to analyze its mRNA and protein expression. In parallel, Calu3 cell lines and PBMCs were in vitro infected with growing doses of SARS-CoV-2 (0.5, 5, 1000 MOI) and HIV-1<sub>BAL</sub> (0.1, 1, and 10 ng p24 HIV-1<sub>Bal</sub>/1 × 10<sup>6</sup> PBMCs) viruses, respectively. Results showed that: (1) ERAP2/Iso3 mRNA expression can be prompted by many pathogens and it is coupled with the modulation of several determinants (cytokines, interferon-stimulated genes, activation/inhibition markers, antigen-presentation elements) orchestrating the anti-microbial immune response (Quantigene); (2) ERAP2/Iso3 mRNA is translated into a protein (western blot); (3) ERAP2/Iso3 mRNA expression is sensitive to SARS-CoV-2 and HIV-1 concentration. Considering the key role played by ERAPs in antigen processing and presentation, it is conceivable that these enzymes may be potential targets and modulators of the pathogenicity of infectious diseases and further analyses are needed to define the role played by the different isoforms. |
| first_indexed | 2024-03-10T16:54:35Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:54:35Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-0e0cf6e66d9c4433881f397a45ecec082023-11-20T11:10:28ZengMDPI AGCells2073-44092020-08-0199195110.3390/cells9091951A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection?Irma Saulle0Claudia Vanetti1Sara Goglia2Chiara Vicentini3Enrico Tombetti4Micaela Garziano5Mario Clerici6Mara Biasin7Department of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, ItalyDepartment of Pathophysiology and Transplantation, University of Milan, 20122 Milan, ItalyDepartment of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, ItalyFollowing influenza infection, rs2248374-G ERAP2 expressing cells may transcribe an alternative spliced isoform: ERAP2/Iso3. This variant, unlike ERAP2-wt, is unable to trim peptides to be loaded on MHC class I molecules, but it can still dimerize with both ERAP2-wt and ERAP1-wt, thus contributing to profiling an alternative cellular immune-peptidome. In order to verify if the expression of ERAP2/Iso3 may be induced by other pathogens, PBMCs and MDMs isolated from 20 healthy subjects were stimulated with flu, LPS, CMV, HIV-AT-2, SARS-CoV-2 antigens to analyze its mRNA and protein expression. In parallel, Calu3 cell lines and PBMCs were in vitro infected with growing doses of SARS-CoV-2 (0.5, 5, 1000 MOI) and HIV-1<sub>BAL</sub> (0.1, 1, and 10 ng p24 HIV-1<sub>Bal</sub>/1 × 10<sup>6</sup> PBMCs) viruses, respectively. Results showed that: (1) ERAP2/Iso3 mRNA expression can be prompted by many pathogens and it is coupled with the modulation of several determinants (cytokines, interferon-stimulated genes, activation/inhibition markers, antigen-presentation elements) orchestrating the anti-microbial immune response (Quantigene); (2) ERAP2/Iso3 mRNA is translated into a protein (western blot); (3) ERAP2/Iso3 mRNA expression is sensitive to SARS-CoV-2 and HIV-1 concentration. Considering the key role played by ERAPs in antigen processing and presentation, it is conceivable that these enzymes may be potential targets and modulators of the pathogenicity of infectious diseases and further analyses are needed to define the role played by the different isoforms.https://www.mdpi.com/2073-4409/9/9/1951ERAP2ERAP2/Iso3microbial infectionsalternative splicingSARS-CoV-2host cell response |
| spellingShingle | Irma Saulle Claudia Vanetti Sara Goglia Chiara Vicentini Enrico Tombetti Micaela Garziano Mario Clerici Mara Biasin A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection? Cells ERAP2 ERAP2/Iso3 microbial infections alternative splicing SARS-CoV-2 host cell response |
| title | A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection? |
| title_full | A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection? |
| title_fullStr | A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection? |
| title_full_unstemmed | A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection? |
| title_short | A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection? |
| title_sort | new erap2 iso3 isoform expression is triggered by different microbial stimuli in human cells could it play a role in the modulation of sars cov 2 infection |
| topic | ERAP2 ERAP2/Iso3 microbial infections alternative splicing SARS-CoV-2 host cell response |
| url | https://www.mdpi.com/2073-4409/9/9/1951 |
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