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Vaccinia Virus Arrests and Shifts the Cell Cycle

Modulation of the host cell cycle is a common strategy used by viruses to create a pro-replicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, the cellular factors...

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Autores principales: Martin, Caroline K., Samolej, Jerzy, Olson, Annabel T., Bertoli, Cosetta, Wiebe, Matthew S., de Bruin, Robertus A. M., Mercer, Jason
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874441/
https://www.ncbi.nlm.nih.gov/pubmed/35216024
http://dx.doi.org/10.3390/v14020431
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author Martin, Caroline K.
Samolej, Jerzy
Olson, Annabel T.
Bertoli, Cosetta
Wiebe, Matthew S.
de Bruin, Robertus A. M.
Mercer, Jason
author_facet Martin, Caroline K.
Samolej, Jerzy
Olson, Annabel T.
Bertoli, Cosetta
Wiebe, Matthew S.
de Bruin, Robertus A. M.
Mercer, Jason
author_sort Martin, Caroline K.
collection PubMed
description Modulation of the host cell cycle is a common strategy used by viruses to create a pro-replicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, the cellular factors and viral effectors that mediate these changes remain unknown. Here, we set out to investigate the effect of VACV infection on cell proliferation and host cell cycle progression. Using a subset of VACV mutants, we characterise the stage of infection required for inhibition of cell proliferation and define the viral effectors required to dysregulate the host cell cycle. Consistent with previous studies, we show that VACV inhibits and subsequently shifts the host cell cycle. We demonstrate that these two phenomena are independent of one another, with viral early genes being responsible for cell cycle inhibition, and post-replicative viral gene(s) responsible for the cell cycle shift. Extending previous findings, we show that the viral kinase F10 is required to activate the DNA damage checkpoint and that the viral B1 kinase and/or B12 pseudokinase mediate degradation of checkpoint effectors p53 and p21 during infection. We conclude that VACV modulates host cell proliferation and host cell cycle progression through temporal expression of multiple VACV effector proteins. (209/200.)
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spelling pubmed-88744412022-02-26 Vaccinia Virus Arrests and Shifts the Cell Cycle Martin, Caroline K. Samolej, Jerzy Olson, Annabel T. Bertoli, Cosetta Wiebe, Matthew S. de Bruin, Robertus A. M. Mercer, Jason Viruses Article Modulation of the host cell cycle is a common strategy used by viruses to create a pro-replicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, the cellular factors and viral effectors that mediate these changes remain unknown. Here, we set out to investigate the effect of VACV infection on cell proliferation and host cell cycle progression. Using a subset of VACV mutants, we characterise the stage of infection required for inhibition of cell proliferation and define the viral effectors required to dysregulate the host cell cycle. Consistent with previous studies, we show that VACV inhibits and subsequently shifts the host cell cycle. We demonstrate that these two phenomena are independent of one another, with viral early genes being responsible for cell cycle inhibition, and post-replicative viral gene(s) responsible for the cell cycle shift. Extending previous findings, we show that the viral kinase F10 is required to activate the DNA damage checkpoint and that the viral B1 kinase and/or B12 pseudokinase mediate degradation of checkpoint effectors p53 and p21 during infection. We conclude that VACV modulates host cell proliferation and host cell cycle progression through temporal expression of multiple VACV effector proteins. (209/200.) MDPI 2022-02-19 /pmc/articles/PMC8874441/ /pubmed/35216024 http://dx.doi.org/10.3390/v14020431 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Martin, Caroline K.
Samolej, Jerzy
Olson, Annabel T.
Bertoli, Cosetta
Wiebe, Matthew S.
de Bruin, Robertus A. M.
Mercer, Jason
Vaccinia Virus Arrests and Shifts the Cell Cycle
title Vaccinia Virus Arrests and Shifts the Cell Cycle
title_full Vaccinia Virus Arrests and Shifts the Cell Cycle
title_fullStr Vaccinia Virus Arrests and Shifts the Cell Cycle
title_full_unstemmed Vaccinia Virus Arrests and Shifts the Cell Cycle
title_short Vaccinia Virus Arrests and Shifts the Cell Cycle
title_sort vaccinia virus arrests and shifts the cell cycle
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874441/
https://www.ncbi.nlm.nih.gov/pubmed/35216024
http://dx.doi.org/10.3390/v14020431
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