Role Reversal of Functional Identity in Host Factors: Dissecting Features Affecting Pro-Viral versus Antiviral Functions of Cellular DEAD-Box Helicases in Tombusvirus Replication

Authors

Cheng-Yu Wu, University of KentuckyFollow
Peter D. Nagy, University of KentuckyFollow

Abstract

Positive-stranded (+)RNA viruses greatly exploit host cells to support viral replication. However, unlike many other pathogens, (+)RNA viruses code for only a limited number of genes, making them highly dependent on numerous co-opted host factors for supporting viral replication and other viral processes during their infections. This excessive dependence on subverted host factors, however, renders (+)RNA viruses vulnerable to host restriction factors that could block virus replication. Interestingly, cellular ATP-dependent DEAD-box RNA helicases could promote or inhibit the replication of Tomato bushy stunt virus (TBSV) replication. However, it is currently unknown what features make a particular DEAD-box helicase either pro-viral or antiviral. In this work, we succeeded in reversing the viral function of the antiviral DDX17-like RH30 DEAD-box helicase by converting it to a pro-viral helicase. We also turned the pro-viral DDX3-like RH20 helicase into an antiviral helicase through deletion of a unique N-terminal domain. We demonstrate that in the absence of the N-terminal domain, the core helicase domain becomes unhinged, showing altered specificity in unwinding viral RNA duplexes containing cis-acting replication elements. The discovery of the sequence plasticity of DEAD-box helicases that can alter recognition of different cis-acting RNA elements in the viral genome illustrates the evolutionary potential of RNA helicases in the arms race between viruses and their hosts, including key roles of RNA helicases in plant innate immunity. Overall, these findings open up the possibility to turn the pro-viral host factors into antiviral factors, thus increasing the potential antiviral arsenal of the host for the benefit of agriculture and health science.

Document Type

Article

Publication Date

10-9-2020

Notes/Citation Information

Published in PLOS Pathogens, v. 16, no. 10, e1008990.

© 2020 Wu, Nagy.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Digital Object Identifier (DOI)

https://doi.org/10.1371/journal.ppat.1008990

Funding Information

This work was supported by the National Institute of Allergy and Infectious Diseases (grant: 1R21AI122078 to PDN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Repository Citation

Wu, Cheng-Yu and Nagy, Peter D., "Role Reversal of Functional Identity in Host Factors: Dissecting Features Affecting Pro-Viral versus Antiviral Functions of Cellular DEAD-Box Helicases in Tombusvirus Replication" (2020). Plant Pathology Faculty Publications. 95.
https://uknowledge.uky.edu/plantpath_facpub/95