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Specific Recognition of the 5′-Untranslated Region of West Nile Virus Genome by Human Innate Immune System

In the last few years, the sudden outbreak of COVID-19 caused by SARS-CoV-2 proved the crucial importance of understanding how emerging viruses work and proliferate, in order to avoid the repetition of such a dramatic sanitary situation with unprecedented social and economic costs. West Nile Virus i...

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Autores principales: Bignon, Emmanuelle, Marazzi, Marco, Miclot, Tom, Barone, Giampaolo, Monari, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227302/
https://www.ncbi.nlm.nih.gov/pubmed/35746753
http://dx.doi.org/10.3390/v14061282
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author Bignon, Emmanuelle
Marazzi, Marco
Miclot, Tom
Barone, Giampaolo
Monari, Antonio
author_facet Bignon, Emmanuelle
Marazzi, Marco
Miclot, Tom
Barone, Giampaolo
Monari, Antonio
author_sort Bignon, Emmanuelle
collection PubMed
description In the last few years, the sudden outbreak of COVID-19 caused by SARS-CoV-2 proved the crucial importance of understanding how emerging viruses work and proliferate, in order to avoid the repetition of such a dramatic sanitary situation with unprecedented social and economic costs. West Nile Virus is a mosquito-borne pathogen that can spread to humans and induce severe neurological problems. This RNA virus caused recent remarkable outbreaks, notably in Europe, highlighting the need to investigate the molecular mechanisms of its infection process in order to design and propose efficient antivirals. Here, we resort to all-atom Molecular Dynamics simulations to characterize the structure of the 5 [Formula: see text]-untranslated region of the West Nile Virus genome and its specific recognition by the human innate immune system via oligoadenylate synthetase. Our simulations allowed us to map the interaction network between the viral RNA and the host protein, which drives its specific recognition and triggers the host immune response. These results may provide fundamental knowledge that can assist further antivirals’ design, including therapeutic RNA strategies.
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spelling pubmed-92273022022-06-25 Specific Recognition of the 5′-Untranslated Region of West Nile Virus Genome by Human Innate Immune System Bignon, Emmanuelle Marazzi, Marco Miclot, Tom Barone, Giampaolo Monari, Antonio Viruses Article In the last few years, the sudden outbreak of COVID-19 caused by SARS-CoV-2 proved the crucial importance of understanding how emerging viruses work and proliferate, in order to avoid the repetition of such a dramatic sanitary situation with unprecedented social and economic costs. West Nile Virus is a mosquito-borne pathogen that can spread to humans and induce severe neurological problems. This RNA virus caused recent remarkable outbreaks, notably in Europe, highlighting the need to investigate the molecular mechanisms of its infection process in order to design and propose efficient antivirals. Here, we resort to all-atom Molecular Dynamics simulations to characterize the structure of the 5 [Formula: see text]-untranslated region of the West Nile Virus genome and its specific recognition by the human innate immune system via oligoadenylate synthetase. Our simulations allowed us to map the interaction network between the viral RNA and the host protein, which drives its specific recognition and triggers the host immune response. These results may provide fundamental knowledge that can assist further antivirals’ design, including therapeutic RNA strategies. MDPI 2022-06-13 /pmc/articles/PMC9227302/ /pubmed/35746753 http://dx.doi.org/10.3390/v14061282 Text en © 2022 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
Bignon, Emmanuelle
Marazzi, Marco
Miclot, Tom
Barone, Giampaolo
Monari, Antonio
Specific Recognition of the 5′-Untranslated Region of West Nile Virus Genome by Human Innate Immune System
title Specific Recognition of the 5′-Untranslated Region of West Nile Virus Genome by Human Innate Immune System
title_full Specific Recognition of the 5′-Untranslated Region of West Nile Virus Genome by Human Innate Immune System
title_fullStr Specific Recognition of the 5′-Untranslated Region of West Nile Virus Genome by Human Innate Immune System
title_full_unstemmed Specific Recognition of the 5′-Untranslated Region of West Nile Virus Genome by Human Innate Immune System
title_short Specific Recognition of the 5′-Untranslated Region of West Nile Virus Genome by Human Innate Immune System
title_sort specific recognition of the 5′-untranslated region of west nile virus genome by human innate immune system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227302/
https://www.ncbi.nlm.nih.gov/pubmed/35746753
http://dx.doi.org/10.3390/v14061282
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