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Updated: Jun 5, 2025

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
CircPTPN11 inhibits the replication of Coxsackievirus B5 through regulating the IFN-I pathway by targeting
Jingru Gao1, Fan Yang2, Jihong Zhang1
1Medical School, Kunming University of Science and Technology, Kunming, Yunnan Province, China.
Abstract:
Coxsackievirus B5 (CVB5) is a major pathogen responsible for hand-foot-mouth disease, herpangina, and even severe death. The mechanisms underlying CVB5-induced diseases are not fully elucidated, and no specific antiviral treatments are currently available. Circular RNAs (circRNAs), a closed-loop molecular structure, have been reported to be involved in virus infectious diseases. However, their roles and mechanisms in CVB5 infection remain largely unknown. In this study, we identify that CircPTPN11 is significantly upregulated following CVB5 infection in RD cells. Characteristic analysis reveals that the expression of CircPTPN11 is both time- and dose-dependent upon CVB5 infection and is specific to intestinal tissue. Moreover, CircPTPN11 inhibits CVB5 replication by activating IRF3 in the type-I interferon (IFN-I) pathway. Further underneath mechanism shows that CircPTPN11 indirectly regulates CVB5 replication by sponging miR-152-3p, and miR-152-3p influences CVB5 replication by interacting with the gene coding for signal regulatory protein alpha (SIRPA). In conclusion, this study suggests that CircPTPN11 targets SIRPA by sponging miR-152-3p, thereby inhibiting the replication and proliferation of CVB5. These findings provide a molecular target for the diagnosis and treatment of CVB5 infection.
Insights
Circular RNA CircPTPN11 is upregulated during Coxsackievirus B5 infection, inhibiting viral replication by activating the type-I interferon pathway and targeting SIRPA via miR-152-3p.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Coxsackievirus B5 (CVB5) causes significant diseases like hand-foot-mouth disease, with unclear mechanisms and no specific treatments.
- Circular RNAs (circRNAs) are implicated in viral infections, but their role in CVB5 is unknown.
Purpose of the Study:
- To investigate the role and mechanism of circRNAs in CVB5 infection.
- To identify potential therapeutic targets for CVB5.
Main Methods:
- CVB5 infection in RD cells to analyze circRNA expression.
- Quantitative analysis of CircPTPN11 expression.
- Investigating the interaction between CircPTPN11, miR-152-3p, and SIRPA.
- Assessing the impact on CVB5 replication and type-I interferon pathway activation.
Main Results:
- CircPTPN11 expression is significantly upregulated in a time- and dose-dependent manner following CVB5 infection, specifically in intestinal tissue.
- CircPTPN11 inhibits CVB5 replication by activating IRF3 in the type-I interferon (IFN-I) pathway.
- CircPTPN11 acts as a molecular sponge for miR-152-3p, which in turn regulates SIRPA expression, ultimately inhibiting CVB5 replication.
Conclusions:
- CircPTPN11 plays a crucial role in antiviral defense against CVB5 by modulating the miR-152-3p/SIRPA axis and activating the IFN-I pathway.
- CircPTPN11 represents a potential molecular target for diagnosing and treating CVB5 infections.
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