SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication
Serine incorporator protein 5 (SERINC5) is a key innate immunity factor that operates in the cell to restrict the infectivity of certain viruses. Different viruses have developed strategies to antagonize SERINC5 function but, how SERINC5 is controlled during viral infection is poorly understood. Her...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1066493/full |
| _version_ | 1828014331479982080 |
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| author | Salvador Meseguer Mari-Paz Rubio Begoña Lainez Beatriz Pérez-Benavente Raúl Pérez-Moraga Sergio Romera-Giner Francisco García-García Olalla Martinez-Macias Antonio Cremades Francisco J. Iborra Oscar Candelas-Rivera Fernando Almazan Enric Esplugues Enric Esplugues |
| author_facet | Salvador Meseguer Mari-Paz Rubio Begoña Lainez Beatriz Pérez-Benavente Raúl Pérez-Moraga Sergio Romera-Giner Francisco García-García Olalla Martinez-Macias Antonio Cremades Francisco J. Iborra Oscar Candelas-Rivera Fernando Almazan Enric Esplugues Enric Esplugues |
| author_sort | Salvador Meseguer |
| collection | DOAJ |
| description | Serine incorporator protein 5 (SERINC5) is a key innate immunity factor that operates in the cell to restrict the infectivity of certain viruses. Different viruses have developed strategies to antagonize SERINC5 function but, how SERINC5 is controlled during viral infection is poorly understood. Here, we report that SERINC5 levels are reduced in COVID-19 patients during the infection by SARS-CoV-2 and, since no viral protein capable of repressing the expression of SERINC5 has been identified, we hypothesized that SARS-CoV-2 non-coding small viral RNAs (svRNAs) could be responsible for this repression. Two newly identified svRNAs with predicted binding sites in the 3′-untranslated region (3’-UTR) of the SERINC5 gene were characterized and we found that the expression of both svRNAs during the infection was not dependent on the miRNA pathway proteins Dicer and Argonaute-2. By using svRNAs mimic oligonucleotides, we demonstrated that both viral svRNAs can bind the 3’UTR of SERINC5 mRNA, reducing SERINC5 expression in vitro. Moreover, we found that an anti-svRNA treatment to Vero E6 cells before SARS-CoV-2 infection recovered the levels of SERINC5 and reduced the levels of N and S viral proteins. Finally, we showed that SERINC5 positively controls the levels of Mitochondrial Antiviral Signalling (MAVS) protein in Vero E6. These results highlight the therapeutic potential of targeting svRNAs based on their action on key proteins of the innate immune response during SARS-CoV-2 viral infection. |
| first_indexed | 2024-04-10T09:59:17Z |
| format | Article |
| id | doaj.art-d321af9aa7e742ea9c65cb9e1f7df3db |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-10T09:59:17Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-d321af9aa7e742ea9c65cb9e1f7df3db2023-02-16T10:54:05ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-02-011410.3389/fmicb.2023.10664931066493SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replicationSalvador Meseguer0Mari-Paz Rubio1Begoña Lainez2Beatriz Pérez-Benavente3Raúl Pérez-Moraga4Sergio Romera-Giner5Francisco García-García6Olalla Martinez-Macias7Antonio Cremades8Francisco J. Iborra9Oscar Candelas-Rivera10Fernando Almazan11Enric Esplugues12Enric Esplugues13Molecular and Cellular Immunology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, SpainMolecular and Cellular Immunology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, SpainMolecular and Cellular Immunology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, SpainMolecular and Cellular Immunology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, SpainBioinformatics and Biostatistics Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, SpainBioinformatics and Biostatistics Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, SpainBioinformatics and Biostatistics Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, SpainHospital Universitario de la Ribera, Valencia, SpainHospital Universitario de la Ribera, Valencia, SpainBiological Noise and Cell Plasticity Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Associated Unit to Instituto de Biomedicina de Valencia-CSIC, Valencia, SpainMolecular and Cellular Biology Department, Centro Nacional de Biotecnología (CNB), CSIC, Madrid, SpainMolecular and Cellular Biology Department, Centro Nacional de Biotecnología (CNB), CSIC, Madrid, SpainMolecular and Cellular Immunology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, SpainDepartment of Comparative Medicine, Yale School of Medicine, New Haven, CT, United StatesSerine incorporator protein 5 (SERINC5) is a key innate immunity factor that operates in the cell to restrict the infectivity of certain viruses. Different viruses have developed strategies to antagonize SERINC5 function but, how SERINC5 is controlled during viral infection is poorly understood. Here, we report that SERINC5 levels are reduced in COVID-19 patients during the infection by SARS-CoV-2 and, since no viral protein capable of repressing the expression of SERINC5 has been identified, we hypothesized that SARS-CoV-2 non-coding small viral RNAs (svRNAs) could be responsible for this repression. Two newly identified svRNAs with predicted binding sites in the 3′-untranslated region (3’-UTR) of the SERINC5 gene were characterized and we found that the expression of both svRNAs during the infection was not dependent on the miRNA pathway proteins Dicer and Argonaute-2. By using svRNAs mimic oligonucleotides, we demonstrated that both viral svRNAs can bind the 3’UTR of SERINC5 mRNA, reducing SERINC5 expression in vitro. Moreover, we found that an anti-svRNA treatment to Vero E6 cells before SARS-CoV-2 infection recovered the levels of SERINC5 and reduced the levels of N and S viral proteins. Finally, we showed that SERINC5 positively controls the levels of Mitochondrial Antiviral Signalling (MAVS) protein in Vero E6. These results highlight the therapeutic potential of targeting svRNAs based on their action on key proteins of the innate immune response during SARS-CoV-2 viral infection.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1066493/fullSARS-CoV-2viral miRNAsSERINC5MAVSinnate immune response |
| spellingShingle | Salvador Meseguer Mari-Paz Rubio Begoña Lainez Beatriz Pérez-Benavente Raúl Pérez-Moraga Sergio Romera-Giner Francisco García-García Olalla Martinez-Macias Antonio Cremades Francisco J. Iborra Oscar Candelas-Rivera Fernando Almazan Enric Esplugues Enric Esplugues SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication Frontiers in Microbiology SARS-CoV-2 viral miRNAs SERINC5 MAVS innate immune response |
| title | SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication |
| title_full | SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication |
| title_fullStr | SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication |
| title_full_unstemmed | SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication |
| title_short | SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication |
| title_sort | sars cov 2 encoded small rnas are able to repress the host expression of serinc5 to facilitate viral replication |
| topic | SARS-CoV-2 viral miRNAs SERINC5 MAVS innate immune response |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1066493/full |
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