Human coronaviruses disassemble processing bodies.

Autor: Kleer M; Microbiology, Immunology and Infectious Diseases Department, University of Calgary, Calgary, Alberta, Canada.; Charbonneau Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada., Mulloy RP; Microbiology, Immunology and Infectious Diseases Department, University of Calgary, Calgary, Alberta, Canada.; Charbonneau Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada., Robinson CA; Microbiology, Immunology and Infectious Diseases Department, University of Calgary, Calgary, Alberta, Canada.; Charbonneau Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada., Evseev D; Microbiology, Immunology and Infectious Diseases Department, University of Calgary, Calgary, Alberta, Canada.; Charbonneau Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada., Bui-Marinos MP; Microbiology, Immunology and Infectious Diseases Department, University of Calgary, Calgary, Alberta, Canada.; Charbonneau Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada., Castle EL; School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada., Banerjee A; Vaccine and Infectious Disease Organization, University of Saskatchewan; Saskatoon, Saskatchewan, Canada.; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan; Saskatoon, Saskatchewan, Canada.; Department of Biology, University of Waterloo; Waterloo, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Mubareka S; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.; Sunnybrook Research Institute, Toronto, Ontario, Canada., Mossman K; Department of Medicine, Master University, Hamilton, Ontario, Canada.; Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada., Corcoran JA; Microbiology, Immunology and Infectious Diseases Department, University of Calgary, Calgary, Alberta, Canada.; Charbonneau Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Aug 23; Vol. 18 (8), pp. e1010724. Date of Electronic Publication: 2022 Aug 23 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1010724
Abstrakt: A dysregulated proinflammatory cytokine response is characteristic of severe coronavirus infections caused by SARS-CoV-2, yet our understanding of the underlying mechanism responsible for this imbalanced immune response remains incomplete. Processing bodies (PBs) are cytoplasmic membraneless ribonucleoprotein granules that control innate immune responses by mediating the constitutive decay or suppression of mRNA transcripts, including many that encode proinflammatory cytokines. PB formation promotes turnover or suppression of cytokine RNAs, whereas PB disassembly corresponds with the increased stability and/or translation of these cytokine RNAs. Many viruses cause PB disassembly, an event that can be viewed as a switch that rapidly relieves cytokine RNA repression and permits the infected cell to respond to viral infection. Prior to this submission, no information was known about how human coronaviruses (CoVs) impacted PBs. Here, we show SARS-CoV-2 and the common cold CoVs, OC43 and 229E, induced PB loss. We screened a SARS-CoV-2 gene library and identified that expression of the viral nucleocapsid (N) protein from SARS-CoV-2 was sufficient to mediate PB disassembly. RNA fluorescent in situ hybridization revealed that transcripts encoding TNF and IL-6 localized to PBs in control cells. PB loss correlated with the increased cytoplasmic localization of these transcripts in SARS-CoV-2 N protein-expressing cells. Ectopic expression of the N proteins from five other human coronaviruses (OC43, MERS, 229E, NL63 and SARS-CoV) did not cause significant PB disassembly, suggesting that this feature is unique to SARS-CoV-2 N protein. These data suggest that SARS-CoV-2-mediated PB disassembly contributes to the dysregulation of proinflammatory cytokine production observed during severe SARS-CoV-2 infection.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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