Schumann, S orcid.org/0000-0002-0227-1360, Jackson, BR, Yule, I et al. (4 more authors) (2016) Targeting the ATP-dependent formation of herpesvirus ribonucleoprotein particle assembly as an antiviral approach. Nature Microbiology, 2. 16201.
Abstract
Human herpesviruses are responsible for a range of debilitating acute and recurrent diseases, including a number of malignancies. Current treatments are limited to targeting the herpesvirus DNA polymerases, however with emerging viral resistance and little efficacy against the oncogenic herpesviruses, there is an urgent need for new antiviral strategies. Herein we describe a mechanism to inhibit the replication of the oncogenic herpesvirus Kaposi’s sarcoma associated herpesvirus (KSHV), by targeting the ATP-dependent formation of viral ribonucleoprotein particles (vRNPs). We demonstrate that small molecule inhibitors which selectively inhibit the ATPase activity of the cellular human transcription/export complex (hTREX) protein UAP56, result in effective inhibition of vRNP formation, viral lytic replication and infectious virion production. Strikingly, as all human herpesviruses utilize conserved mRNA processing pathways involving hTREX components, we demonstrate the feasibility of this approach for pan-herpesvirus inhibition.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | (c) 2016, Macmillan Publishers Limited, part of Springer Nature. All rights reserved. This is an author produced version of a paper published in Nature Microbiology. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Molecular Biology (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 23 Sep 2016 14:03 |
Last Modified: | 05 Nov 2017 11:08 |
Published Version: | https://doi.org/10.1038/nmicrobiol.2016.201 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/nmicrobiol.2016.201 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:104272 |