SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication.
Por:
Meseguer S, Rubio MP, Lainez B, Pérez-Benavente B, Pérez-Moraga R, Romera-Giner S, García-García F, Martinez-Macias O, Cremades A, Iborra FJ, Candelas-Rivera O, Almazan F and Esplugues E
Publicada:
16 feb 2023
Resumen:
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.
Filiaciones:
:
Molecular and Cellular Immunology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
Rubio MP:
Molecular and Cellular Immunology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
Lainez B:
Molecular and Cellular Immunology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
Pérez-Benavente B:
Molecular and Cellular Immunology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
:
Bioinformatics and Biostatistics Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
:
Bioinformatics and Biostatistics Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
:
Bioinformatics and Biostatistics Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
Martinez-Macias O:
Hospital Universitario de la Ribera, Valencia, Spain
Cremades A:
Hospital Universitario de la Ribera, Valencia, Spain
:
Biological Noise and Cell Plasticity Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Associated Unit to Instituto de Biomedicina de Valencia-CSIC, Valencia, Spain
Candelas-Rivera O:
Molecular and Cellular Biology Department, Centro Nacional de Biotecnología (CNB), CSIC, Madrid, Spain
Almazan F:
Molecular and Cellular Biology Department, Centro Nacional de Biotecnología (CNB), CSIC, Madrid, Spain
:
Molecular and Cellular Immunology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
Department of Comparative Medicine, Yale School of Medicine, New Haven, CT, United States
gold, Green Published
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