RIG-I Recognizes the 5′ Region of Dengue and Zika Virus Genomes
Summary: The flavivirus genus comprises major human pathogens, such as Dengue (DENV) and Zika (ZIKV) viruses. RIG-I and MDA5 are key cytoplasmic pathogen recognition receptors that are implicated in detecting viral RNAs. Here, we show that RNAs that co-purified with RIG-I during DENV infection are i...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718309574 |
| _version_ | 1831570322275434496 |
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| author | Maxime Chazal Guillaume Beauclair Ségolène Gracias Valérie Najburg Etienne Simon-Lorière Frédéric Tangy Anastassia V. Komarova Nolwenn Jouvenet |
| author_facet | Maxime Chazal Guillaume Beauclair Ségolène Gracias Valérie Najburg Etienne Simon-Lorière Frédéric Tangy Anastassia V. Komarova Nolwenn Jouvenet |
| author_sort | Maxime Chazal |
| collection | DOAJ |
| description | Summary: The flavivirus genus comprises major human pathogens, such as Dengue (DENV) and Zika (ZIKV) viruses. RIG-I and MDA5 are key cytoplasmic pathogen recognition receptors that are implicated in detecting viral RNAs. Here, we show that RNAs that co-purified with RIG-I during DENV infection are immuno-stimulatory, whereas RNAs bound to MDA5 are not. An affinity purification method combined with next-generation sequencing (NGS) revealed that the 5′ region of the DENV genome is recognized by RIG-I. No DENV RNA was bound to MDA5. In vitro production of fragments of the DENV genome confirmed the NGS data and revealed that the 5′ end of the genome, when bearing 5′-triphosphates, is the RIG-I ligand. The 5′ region of the ZIKV genome is also a RIG-I agonist. We propose that RIG-I binds to the highly structured and conserved 5′ region of flavivirus nascent transcripts before capping and that this mechanism leads to interferon secretion by infected cells. : Using a panel of techniques, including a ribonucleoproteomic approach based on tagged protein affinity purification combined with next-generation sequencing, Chazal et al. show that the cytoplasmic sensor RIG-I plays a key role in cellular defense against Dengue and Zika viruses. Keywords: flavivirus, Dengue virus, Zika virus, innate immunity, antiviral immunity, pathogen recognition receptors, RIG-I, MDA5, riboproteomic approach |
| first_indexed | 2024-12-17T12:49:15Z |
| format | Article |
| id | doaj.art-963cc1426b324aa49de56b7779c61c56 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-17T12:49:15Z |
| publishDate | 2018-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-963cc1426b324aa49de56b7779c61c562022-12-21T21:47:39ZengElsevierCell Reports2211-12472018-07-01242320328RIG-I Recognizes the 5′ Region of Dengue and Zika Virus GenomesMaxime Chazal0Guillaume Beauclair1Ségolène Gracias2Valérie Najburg3Etienne Simon-Lorière4Frédéric Tangy5Anastassia V. Komarova6Nolwenn Jouvenet7Unité Génomique Virale et Vaccination, Département de Virologie, CNRS UMR 3569, Institut Pasteur, Paris 75015, France; Unité de Génétique Fonctionnelle des Maladies Infectieuses, Institut Pasteur, Paris 75015, France; CNRS UMR2000 Génomique Évolutive, Modélisation et Santé, Institut Pasteur, Paris 75015, FranceUnité Génomique Virale et Vaccination, Département de Virologie, CNRS UMR 3569, Institut Pasteur, Paris 75015, FranceUnité Génomique Virale et Vaccination, Département de Virologie, CNRS UMR 3569, Institut Pasteur, Paris 75015, FranceUnité Génomique Virale et Vaccination, Département de Virologie, CNRS UMR 3569, Institut Pasteur, Paris 75015, FranceUnité de Génétique Fonctionnelle des Maladies Infectieuses, Institut Pasteur, Paris 75015, France; CNRS UMR2000 Génomique Évolutive, Modélisation et Santé, Institut Pasteur, Paris 75015, FranceUnité Génomique Virale et Vaccination, Département de Virologie, CNRS UMR 3569, Institut Pasteur, Paris 75015, FranceUnité Génomique Virale et Vaccination, Département de Virologie, CNRS UMR 3569, Institut Pasteur, Paris 75015, France; Corresponding authorUnité Génomique Virale et Vaccination, Département de Virologie, CNRS UMR 3569, Institut Pasteur, Paris 75015, France; Corresponding authorSummary: The flavivirus genus comprises major human pathogens, such as Dengue (DENV) and Zika (ZIKV) viruses. RIG-I and MDA5 are key cytoplasmic pathogen recognition receptors that are implicated in detecting viral RNAs. Here, we show that RNAs that co-purified with RIG-I during DENV infection are immuno-stimulatory, whereas RNAs bound to MDA5 are not. An affinity purification method combined with next-generation sequencing (NGS) revealed that the 5′ region of the DENV genome is recognized by RIG-I. No DENV RNA was bound to MDA5. In vitro production of fragments of the DENV genome confirmed the NGS data and revealed that the 5′ end of the genome, when bearing 5′-triphosphates, is the RIG-I ligand. The 5′ region of the ZIKV genome is also a RIG-I agonist. We propose that RIG-I binds to the highly structured and conserved 5′ region of flavivirus nascent transcripts before capping and that this mechanism leads to interferon secretion by infected cells. : Using a panel of techniques, including a ribonucleoproteomic approach based on tagged protein affinity purification combined with next-generation sequencing, Chazal et al. show that the cytoplasmic sensor RIG-I plays a key role in cellular defense against Dengue and Zika viruses. Keywords: flavivirus, Dengue virus, Zika virus, innate immunity, antiviral immunity, pathogen recognition receptors, RIG-I, MDA5, riboproteomic approachhttp://www.sciencedirect.com/science/article/pii/S2211124718309574 |
| spellingShingle | Maxime Chazal Guillaume Beauclair Ségolène Gracias Valérie Najburg Etienne Simon-Lorière Frédéric Tangy Anastassia V. Komarova Nolwenn Jouvenet RIG-I Recognizes the 5′ Region of Dengue and Zika Virus Genomes Cell Reports |
| title | RIG-I Recognizes the 5′ Region of Dengue and Zika Virus Genomes |
| title_full | RIG-I Recognizes the 5′ Region of Dengue and Zika Virus Genomes |
| title_fullStr | RIG-I Recognizes the 5′ Region of Dengue and Zika Virus Genomes |
| title_full_unstemmed | RIG-I Recognizes the 5′ Region of Dengue and Zika Virus Genomes |
| title_short | RIG-I Recognizes the 5′ Region of Dengue and Zika Virus Genomes |
| title_sort | rig i recognizes the 5 region of dengue and zika virus genomes |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718309574 |
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