Veterinary and Biomedical Sciences, Department of
ORCID IDs
Jerzy Samolej https://orcid.org/0000-0003-0615-3297
Matthew S. Wiebe https://orcid.org/0000-0001-6337-6556
Robertus A. M. de Bruin https://orcid.org/0000-0001-9957-1409
Date of this Version
2-19-2022
Citation
Martin, C.K.; Samolej, J.; Olson, A.T.; Bertoli, C.;Wiebe, M.S.; de Bruin, R.A.M.; Mercer, J. Vaccinia Virus Arrests and Shifts the Cell Cycle. Viruses 2022, 14, 431. https://doi.org/10.3390/v14020431
Abstract
Modulation of the host cell cycle is a common strategy used by viruses to create a proreplicative 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.)
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Cell and Developmental Biology Commons, Immunology and Infectious Disease Commons, Medical Sciences Commons, Veterinary Microbiology and Immunobiology Commons, Veterinary Pathology and Pathobiology Commons
Comments
© 2022 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 (https:// creativecommons.org/licenses/by/ 4.0/).