P53-Independent G1-Cell Cycle Arrest Increases SARS-CoV-2 RNA Replication.

Autor:	Husser C; Department of Laboratory Medicine, Unit of Clinical Microbiology, Karolinska Institutet, 171 77 Stockholm, Sweden., Kwon H; National Veterinary Institute, 751 89 Uppsala, Sweden., Andersson K; Biomedrex Genetics, 141 52 Huddinge, Sweden., Appelberg S; Department of Microbiology, Public Health Agency of Sweden, 171 65 Solna, Sweden., Montserrat N; University of Barcelona, 08028 Barcelona, Spain 08028 Barcelona, Spain.; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), University of Barcelona, 08028 Barcelona, Spain.; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain., Mirazimi A; Department of Laboratory Medicine, Unit of Clinical Microbiology, Karolinska Institutet, 171 77 Stockholm, Sweden.; National Veterinary Institute, 751 89 Uppsala, Sweden.; Department of Microbiology, Public Health Agency of Sweden, 171 65 Solna, Sweden., Monteil VM; Department of Laboratory Medicine, Unit of Clinical Microbiology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Microorganisms [Microorganisms] 2024 Feb 22; Vol. 12 (3). Date of Electronic Publication: 2024 Feb 22.
DOI:	10.3390/microorganisms12030443
Abstrakt:	While having already killed more than 7 million of people worldwide in 4 years, SARS-CoV-2, the etiological agent of COVID-19, is still circulating and evolving. Understanding the pathogenesis of the virus is of capital importance. It was shown that in vitro and in vivo infection with SARS-CoV-2 can lead to cell cycle arrest but the effect of the cell cycle arrest on the virus infection and the associated mechanisms are still unclear. By stopping cells in the G1 phase as well as targeting several pathways involved using inhibitors and small interfering RNAs, we were able to determine that the cell cycle arrest in the late G1 is beneficial for SARS-CoV-2 replication. This cell cycle arrest is independent of p53 but is dependent on the CDC25A-CDK2/cyclin E pathway. These data give a new understanding in SARS-CoV-2 pathogenesis and highlight some possible targets for the development of novel therapeutic approaches.
Databáze:	MEDLINE
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