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The Endogenous RIG-I Ligand Is Generated in Influenza A-Virus Infected Cells
As a result of a viral infection, viral genomes are not only recognized by RIG-I, but also lead to the activation of RNase L, which cleaves cellular RNA to generate the endogenous RIG-I ligand (eRL). The eRL was previously identified as a specific sequence derived from the internal transcribed space...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402674/ https://www.ncbi.nlm.nih.gov/pubmed/34452429 http://dx.doi.org/10.3390/v13081564 |
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author | Steinberg, Julia Wadenpohl, Timo Jung, Stephanie |
author_facet | Steinberg, Julia Wadenpohl, Timo Jung, Stephanie |
author_sort | Steinberg, Julia |
collection | PubMed |
description | As a result of a viral infection, viral genomes are not only recognized by RIG-I, but also lead to the activation of RNase L, which cleaves cellular RNA to generate the endogenous RIG-I ligand (eRL). The eRL was previously identified as a specific sequence derived from the internal transcribed spacer region 2, which bears a 2′3′ cyclic phosphate instead of the common 5′ triphosphate. By now, the generation of the eRL and its immunostimulatory effect were shown both in vitro and in reporter systems. In this work, we aimed to elucidate whether the eRL is also generated in Influenza A (IAV) and vesicular stomatitis virus (VSV) infected cells. RNA was extracted from virus-infected cells and used for immunostimulations as well as specific PCR-strategies to detect eRL cleavage. We show that the eRL is generated in IAV infected HEK293 cells, but we could not detect specific eRL fragments in VSV infected cells. Further, RIG-I mediated IFN-response depends not only on viral genomes but also on the eRL, as immunostimulatory properties remain present under 5′triphosphate degrading conditions. In summary, we prove the IAV infection induced eRL generation in HEK293 cells, amplifying the innate immune response. |
format | Online Article Text |
id | pubmed-8402674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84026742021-08-29 The Endogenous RIG-I Ligand Is Generated in Influenza A-Virus Infected Cells Steinberg, Julia Wadenpohl, Timo Jung, Stephanie Viruses Article As a result of a viral infection, viral genomes are not only recognized by RIG-I, but also lead to the activation of RNase L, which cleaves cellular RNA to generate the endogenous RIG-I ligand (eRL). The eRL was previously identified as a specific sequence derived from the internal transcribed spacer region 2, which bears a 2′3′ cyclic phosphate instead of the common 5′ triphosphate. By now, the generation of the eRL and its immunostimulatory effect were shown both in vitro and in reporter systems. In this work, we aimed to elucidate whether the eRL is also generated in Influenza A (IAV) and vesicular stomatitis virus (VSV) infected cells. RNA was extracted from virus-infected cells and used for immunostimulations as well as specific PCR-strategies to detect eRL cleavage. We show that the eRL is generated in IAV infected HEK293 cells, but we could not detect specific eRL fragments in VSV infected cells. Further, RIG-I mediated IFN-response depends not only on viral genomes but also on the eRL, as immunostimulatory properties remain present under 5′triphosphate degrading conditions. In summary, we prove the IAV infection induced eRL generation in HEK293 cells, amplifying the innate immune response. MDPI 2021-08-07 /pmc/articles/PMC8402674/ /pubmed/34452429 http://dx.doi.org/10.3390/v13081564 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Steinberg, Julia Wadenpohl, Timo Jung, Stephanie The Endogenous RIG-I Ligand Is Generated in Influenza A-Virus Infected Cells |
title | The Endogenous RIG-I Ligand Is Generated in Influenza A-Virus Infected Cells |
title_full | The Endogenous RIG-I Ligand Is Generated in Influenza A-Virus Infected Cells |
title_fullStr | The Endogenous RIG-I Ligand Is Generated in Influenza A-Virus Infected Cells |
title_full_unstemmed | The Endogenous RIG-I Ligand Is Generated in Influenza A-Virus Infected Cells |
title_short | The Endogenous RIG-I Ligand Is Generated in Influenza A-Virus Infected Cells |
title_sort | endogenous rig-i ligand is generated in influenza a-virus infected cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402674/ https://www.ncbi.nlm.nih.gov/pubmed/34452429 http://dx.doi.org/10.3390/v13081564 |
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