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Published on: December 23, 2020
The Role of Coronavirus RNA-Processing Enzymes in Innate Immune Evasion
Georgia Mandilara1, Marianna A Koutsi2, Marios Agelopoulos2
1National Reference Centre for Salmonella and Shigella, School of Public Health, University of West Attica, 11521 Athens, Greece.
Abstract:
Viral RNA sensing triggers innate antiviral responses in humans by stimulating signaling pathways that include crucial antiviral genes such as interferon. RNA viruses have evolved strategies to inhibit or escape these mechanisms. Coronaviruses use multiple enzymes to synthesize, modify, and process their genomic RNA and sub-genomic RNAs. These include Nsp15 and Nsp16, whose respective roles in RNA capping and dsRNA degradation play a crucial role in coronavirus escape from immune surveillance. Evolutionary studies on coronaviruses demonstrate that genome expansion in Nidoviruses was promoted by the emergence of Nsp14-ExoN activity and led to the acquisition of Nsp15- and Nsp16-RNA-processing activities. In this review, we discuss the main RNA-sensing mechanisms in humans as well as recent structural, functional, and evolutionary insights into coronavirus Nsp15 and Nsp16 with a view to potential antiviral strategies.
Insights
Coronaviruses evade human antiviral defenses using enzymes like Nsp15 and Nsp16 to process viral RNA. Understanding these viral RNA processing mechanisms is key to developing new antiviral therapies.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Human innate immunity detects viral RNA, triggering antiviral responses like interferon production.
- RNA viruses, including coronaviruses, possess mechanisms to evade these immune defenses.
- Coronaviruses utilize enzymes such as Nsp15 and Nsp16 for viral RNA synthesis, modification, and processing.
Purpose of the Study:
- To review human RNA-sensing mechanisms.
- To discuss structural, functional, and evolutionary aspects of coronavirus Nsp15 and Nsp16.
- To explore potential antiviral strategies targeting these viral RNA processing enzymes.
Main Methods:
- Literature review of RNA sensing pathways.
- Analysis of structural and functional data for Nsp15 and Nsp16.
- Examination of evolutionary studies on Nidovirus genome expansion and RNA processing activities.
Main Results:
- Nsp15 and Nsp16 are critical for coronavirus immune evasion through dsRNA degradation and RNA capping.
- Evolutionary analysis links Nsp14-ExoN activity to genome expansion and acquisition of Nsp15/Nsp16 functions.
- These enzymes are central to the coronavirus lifecycle and immune suppression.
Conclusions:
- Coronavirus Nsp15 and Nsp16 play vital roles in evading host immune surveillance.
- Targeting these essential viral RNA processing enzymes offers a promising avenue for antiviral drug development.
- Further research into the structure-function relationships of Nsp15 and Nsp16 can guide the design of novel therapeutics.
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