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Carbenoxolone-mediated cytotoxicity inhibits Vaccinia virus replication in a human keratinocyte cell line

Haga, Ismar R.; Simpson, Jennifer L.; Hawes, Philippa C.; Beard, Philippa M.

Carbenoxolone-mediated cytotoxicity inhibits Vaccinia virus replication in a human keratinocyte cell line Thumbnail


Authors

Ismar R. Haga

Jennifer L. Simpson

Philippa C. Hawes



Abstract

The re-emergence of poxviral zoonotic infections and the threat of bioterrorism emphasise the demand
for efective antipoxvirus therapies. Here, we show that carbenoxolone, a pharmacological inhibitor of
gap junction function and a compound widely used in cell culture, is capable of hindering the replication
of Vaccinia virus, the prototypical poxvirus, in a gap junction-independent manner in a human
keratinocyte cell line. Viral protein synthesis occurs in the presence of carbenoxolone but infectious
virion formation is minimal, indicating that carbenoxolone blocks viral morphogenesis. Initial viability
tests suggested that carbenoxolone was not toxic to cells. However, electron microscopic analysis of
carbenoxolone treated cells revealed that it alters the cellular endomembrane system. This widespread
ultrastructural damage prevents Vaccinia virus virion assembly. These results strengthen the need for
thorough characterisation of the effects of antiviral compounds on the cellular ultrastructure.

Journal Article Type Article
Acceptance Date Oct 8, 2018
Publication Date Nov 16, 2018
Journal Scientific Reports
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 8
Article Number 16956
DOI https://doi.org/10.1038/s41598-018-34732-w
Publisher URL https://www.nature.com/articles/s41598-018-34732-w

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