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Cholic Acid Attenuates ER Stress-Induced Cell Death in Coxsackievirus-B3 Infection
Jae-Young Han1, Hae In Jeong2, Cheol-Woo Park1
1Department of Biomedical Science, Jungwon University, Goesan-gun 23026, Republic of Korea.
Insights
Cholic acid demonstrates antiviral properties against Coxsackievirus Type B3 (CVB3) by inhibiting viral replication and reducing cellular stress. This natural compound shows potential as a therapeutic agent for enterovirus infections.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- Coxsackievirus Type B3 (CVB3) is an enterovirus causing significant human diseases like myocarditis.
- Current therapeutic options for enterovirus infections remain limited, necessitating the search for novel antiviral agents.
Purpose of the Study:
- To identify potential inhibitors of CVB3 replication using a cell-based screening approach.
- To evaluate the antiviral activity of cholic acid against CVB3 infection in HeLa cells.
Main Methods:
- HeLa cells were infected with CVB3 and treated with varying concentrations of cholic acid.
- Viral replication was assessed by measuring viral capsid protein VP1 production via Western blot.
- Cellular responses including translation initiation factor cleavage, ERK signaling, and ER stress markers (ATF4) were analyzed using Western blot and RT-PCR.
Main Results:
- Cholic acid treatment significantly reduced viral capsid protein VP1 production.
- Cholic acid inhibited the cleavage of translation initiation factor eIF4G1 and suppressed ERK signaling.
- CVB3 RNA genome and ATF4 mRNA levels were significantly decreased, indicating reduced viral proliferation and ER stress.
Conclusions:
- Cholic acid exhibits potent antiviral activity against CVB3 by inhibiting viral replication and mitigating ER stress.
- Cholic acid represents a promising candidate for development as a safe, natural therapeutic agent for enterovirus infections.
Abstract:
Coxsackievirus Type B3 (CVB3) is an enterovirus that belongs to the Picornaviridae and causes various diseases such as myocarditis and hand-foot-mouth disease. However, an effective antiviral drug is still not developed. In this study, we looked for potential inhibitors of CVB3 replication by examining the survival of CVB3-infected HeLa cells. We detected an antiviral effect by cholic acid and identified it as a candidate inhibitor of CVB3 replication. Cholic acid circulates in the liver and intestines, and it helps the digestion and absorption of lipids in the small intestine. HeLa cells were cultured in 12-well plates and treated with cholic acid (1 and 10 μg/ml) and 10⁶ PFU/ml of CVB3. After 16 h post-infection, the cells were lysed and subjected to western blot analysis and RT-PCR. The production of the viral capsid protein VP1 was dramatically decreased, and translation initiation factor eIF4G1 cleavage was significantly inhibited by treatment with 10 μg/ml cholic acid. Moreover, cholic acid inhibited ERK signaling in CVB3-infected HeLa cells. RT-PCR showed that the amounts of the CVB3 RNA genome and mRNA for the ER stress-related transcription factor ATF4 were significantly reduced. These results showed that cholic acid strongly reduced ER stress and CVB3 proliferation. This compound can be developed as a safe natural therapeutic agent for enterovirus infections.