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Modulation of Ire1-Xbp1 Defense Pathway in Encephalomyocarditis Virus-Infected HeLa Cells
Anna Shishova1,2, Yury Ivin1, Ekaterina Gladneva1
1Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), 108819 Moscow, Russia.
Viruses
|March 27, 2025
Summary
Encephalomyocarditis virus suppresses a key cellular defense pathway called the unfolded protein response (UPR). This virus interferes with the IRE1-XBP1 signaling, hindering the cell's ability to manage endoplasmic reticulum stress.
Area of Science:
- Virology
- Cellular Biology
- Immunology
Background:
- Viral pathogenicity often involves subverting host cellular defense mechanisms.
- The unfolded protein response (UPR) is a critical cellular pathway that mitigates endoplasmic reticulum (ER) stress.
- IRE1-mediated splicing of XBP1 mRNA is a major branch of the UPR, leading to increased transcription factor activity.
Purpose of the Study:
- To investigate the interaction between Encephalomyocarditis Virus (EMCV) and the IRE1-dependent UPR pathway.
- To determine if EMCV can modulate the activation of XBP1 mRNA splicing.
- To elucidate the role of EMCV infection in cellular defense against ER stress.
Main Methods:
- Infection of HeLa cells with EMCV.
- Monitoring of phosphorylated IRE1 levels during viral infection.
- Quantification of spliced XBP1 mRNA accumulation in infected and mock-infected cells.
- Treatment with dithiothreitol (DTT) to induce ER stress in infected and mock-infected cells.
Main Results:
- EMCV infection modulated phosphorylated IRE1 levels in HeLa cells.
- Viral infection did not lead to the accumulation of spliced XBP1 mRNA.
- Infected cells treated with DTT showed significantly lower spliced XBP1 mRNA levels compared to mock-infected cells.
Conclusions:
- Encephalomyocarditis Virus effectively suppresses the IRE1-dependent UPR pathway.
- Picornaviruses possess the ability to modulate host cellular defense mechanisms, specifically the unfolded protein response.
- This viral immune evasion strategy may contribute to viral pathogenicity.
