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The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086627/ https://www.ncbi.nlm.nih.gov/pubmed/27783035 http://dx.doi.org/10.3390/v8100295 |
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author | Cohen, Tobias Schwarz, Toni M. Vigant, Frederic Gardner, Thomas J. Hernandez, Rosmel E. Lee, Benhur Tortorella, Domenico |
author_facet | Cohen, Tobias Schwarz, Toni M. Vigant, Frederic Gardner, Thomas J. Hernandez, Rosmel E. Lee, Benhur Tortorella, Domenico |
author_sort | Cohen, Tobias |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5086627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-50866272016-11-02 The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus Cohen, Tobias Schwarz, Toni M. Vigant, Frederic Gardner, Thomas J. Hernandez, Rosmel E. Lee, Benhur Tortorella, Domenico Viruses Article 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. MDPI 2016-10-24 /pmc/articles/PMC5086627/ /pubmed/27783035 http://dx.doi.org/10.3390/v8100295 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cohen, Tobias Schwarz, Toni M. Vigant, Frederic Gardner, Thomas J. Hernandez, Rosmel E. Lee, Benhur Tortorella, Domenico The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus |
title | The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus |
title_full | The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus |
title_fullStr | The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus |
title_full_unstemmed | The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus |
title_short | The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus |
title_sort | microtubule inhibitor podofilox inhibits an early entry step of human cytomegalovirus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086627/ https://www.ncbi.nlm.nih.gov/pubmed/27783035 http://dx.doi.org/10.3390/v8100295 |
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