Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Stress Granules Inhibit Coxsackievirus B3-Mediated Cell Death via Reduction of Mitochondrial Reactive Oxygen Species and Viral Extracellular Release

  • Ji-Ye Park (BK21 Graduate Program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital) ;
  • Ok Sarah Shin (BK21 Graduate Program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital)
  • Received : 2022.10.17
  • Accepted : 2023.01.03
  • Published : 2023.05.28
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Abstract

Stress granules (SGs) are cytoplasmic aggregates of RNA-protein complexes that form in response to various cellular stresses and are known to restrict viral access to host translational machinery. However, the underlying molecular mechanisms of SGs during viral infections require further exploration. In this study, we evaluated the effect of SG formation on cellular responses to coxsackievirus B3 (CVB3) infection. Sodium arsenite (AS)-mediated SG formation suppressed cell death induced by tumor necrosis factor-alpha (TNF-a)/cycloheximide (CHX) treatment in HeLa cells, during which G3BP1, an essential SG component, contributed to the modulation of apoptosis pathways. SG formation in response to AS treatment blocked CVB3-mediated cell death, possibly via the reduction of mitochondrial reactive oxygen species. Furthermore, we examined whether AS treatment would affect small extracellular vesicle (sEV) formation and secretion during CVB3 infection and modulate human monocytic cell (THP-1) response. CVB3-enriched sEVs isolated from HeLa cells were able to infect and replicate THP-1 cells without causing cytotoxicity. Interestingly, sEVs from AS-treated HeLa cells inhibited CVB3 replication in THP-1 cells. These findings suggest that SG formation during CVB3 infection modulates cellular response by inhibiting the release of CVB3-enriched sEVs.

Keywords

Acknowledgement

This research was funded by the Basic Science Research Program of the National Research Foundation of Korea (NRF) by the Ministry of Science, ICT & Future Planning (NRF-2019R1A2C1005961).

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