4.6 Article

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

期刊

VIRUSES-BASEL
卷 14, 期 6, 页码 -

出版社

MDPI
DOI: 10.3390/v14061282

关键词

West Nile Virus; oligoadenylate synthetase 1; 5 '-untranslated region; recognition mechanism; immune system; emerging viruses

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资金

  1. ANR
  2. CGI [Labex SEAM ANR 11 LABX 086, ANR 11 IDEX 05 02]
  3. IdEx Universite Paris 2019 [ANR-18-IDEX-0001]
  4. CNRS
  5. French Ministry of Higher Education Research and Innovation (MESRI)
  6. DISCOVER-UAH-CM project [REACT UE-CM2021-01]

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The outbreak of COVID-19 emphasized the importance of understanding emerging viruses, while investigating the molecular mechanisms of West Nile Virus can aid in designing effective antivirals.
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'-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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