P53-Independent G1-Cell Cycle Arrest Increases SARS-CoV-2 RNA Replication-Reference-Cited by-同舟云学术

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

Published:2024-02-22 Issue:3 Volume:12 Page:443
ISSN:2076-2607
Container-title:Microorganisms
language:en
Short-container-title:Microorganisms

Author:

Husser Clara¹^ORCID,Kwon Hyesoo²^ORCID,Andersson Klara³,Appelberg Sofia⁴,Montserrat Nuria⁵⁶⁷,Mirazimi Ali¹²⁴,Monteil Vanessa M.¹^ORCID

Affiliation:

1. Department of Laboratory Medicine, Unit of Clinical Microbiology, Karolinska Institutet, 171 77 Stockholm, Sweden

2. National Veterinary Institute, 751 89 Uppsala, Sweden

3. Biomedrex Genetics, 141 52 Huddinge, Sweden

4. Department of Microbiology, Public Health Agency of Sweden, 171 65 Solna, Sweden

5. University of Barcelona, 08028 Barcelona, Spain 08028 Barcelona, Spain

6. Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), University of Barcelona, 08028 Barcelona, Spain

7. Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain

Abstract

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.

Funder

Karolinska Institutet

European Union’s Horizon 2020

Innovative Medicines Initiative 2 Joint Undertaking

Fundació la Marató de TV3

European Union

Publisher

MDPI AG

Link

https://www.mdpi.com/2076-2607/12/3/443/pdf

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