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Viruses 2016, 8(10), 295; doi:10.3390/v8100295

The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 29 April 2016 / Revised: 11 October 2016 / Accepted: 14 October 2016 / Published: 24 October 2016
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [2723 KB, uploaded 25 October 2016]   |  

Abstract

Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion event at the cell membrane or endocytic vesicle. A recent high-throughput screen to identify compounds that block a step prior to viral gene expression identified podofilox as a potent and nontoxic inhibitor. Time-of-addition studies in combination with quantitative-PCR analysis demonstrated that podofilox limits an early step of virus entry at the cell surface. Podofilox was also able to drastically reduce infection by herpes simplex 1, an α-herpesvirus with a very similar entry process to CMV. Podofilox caused a reduced maximal plateau inhibition of infection by viruses with single step binding processes prior to fusion-like Newcastle disease virus, Sendai virus, and influenza A virus or viruses that enter via endocytosis like vesicular stomatitis virus and a clinical-like strain of CMV. These results indicate that microtubules appear to be participating in the post-binding step of virus entry including the pre- and post-penetration events. Modulation of the plasma membrane is required to promote virus entry for herpesviruses, and that podofilox, unlike colchicine or nocodazole, is able to preferentially target microtubule networks at the plasma membrane. View Full-Text
Keywords: cytomegalovirus; microtubules; virus entry; podofilox; colchicine; nocodazole cytomegalovirus; microtubules; virus entry; podofilox; colchicine; nocodazole
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Cohen, T.; Schwarz, T.M.; Vigant, F.; Gardner, T.J.; Hernandez, R.E.; Lee, B.; Tortorella, D. The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus. Viruses 2016, 8, 295.

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