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The Common Immune Responses Differences from Transcriptomic Profiling in Cardiomyocytes upon Coxsackievirus B5 and
Yi Xu1, Xianwu Lan1, Jianwei Chen1
1Department of Cardiology, Guangzhou Overseas Chinese Hospital, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Insights
Viral myocarditis (VMC) involves enterovirus infections. This study compared Coxsackievirus B5 and Echovirus 6 in human cardiomyocytes, revealing key immune responses and Ribavirin
Area of Science:
- Cardiology
- Virology
- Immunology
Background:
- Viral myocarditis (VMC) is a serious heart condition often caused by enteroviruses.
- The precise mechanisms of VMC pathogenesis by enteroviruses are not fully understood.
- Investigating host immune responses in cardiomyocytes is crucial for understanding VMC.
Purpose of the Study:
- To compare the host immune response transcriptomics of human cardiomyocytes infected with Coxsackievirus B5 (CVB5) and Echovirus 6 (ECHO6).
- To identify common immune and inflammatory gene expression patterns induced by CVB5 and ECHO6.
- To evaluate the antiviral effect of Ribavirin against these enteroviruses in cardiomyocytes.
Main Methods:
- Infection of human cardiomyocyte AC16 cells with CVB5 and ECHO6.
- Transcriptomic analysis to assess gene expression changes.
- Quantitative PCR (qPCR) to validate key gene expressions.
- Assessment of Ribavirin's inhibitory effect on viral replication.
Main Results:
- Both CVB5 and ECHO6 efficiently infected AC16 cells, causing viral replication and cytopathic effects.
- Transcriptomic analysis revealed significant upregulation of immune and inflammation-related genes (e.g., IL6, CCL3, IFNL1) in response to both viruses.
- Ribavirin (50 µm) demonstrated significant inhibition of CVB5 and ECHO6 replication.
Conclusions:
- Innate immunity and inflammatory responses are critical in cardiomyocyte defense against enterovirus infection.
- CVB5 and ECHO6 infections induce shared transcriptomic and immune profiles in human cardiomyocytes.
- Ribavirin shows potential as a therapeutic agent for enterovirus-induced myocarditis.
Abstract:
Viral myocarditis (VMC) is a myocardial injury syndrome caused by enterovirus infections, including Coxsackievirus B5 (CVB5) and Echovirus 6 (ECHO6). However, the exact pathogenesis of VMC by enteroviruses remains unclear. Here, the host immune response differences in transcriptomics in human cardiomyocyte AC16 cells upon CVB5 and ECHO6 infections were explored. CVB5 and ECHO6 effectively infected AC16 cells, showing significant viral replication and cytopathic effects at 48 h post-infection. Transcriptomic analysis indicated that both CVB5 and ECHO6 infection induced a series of immune- and inflammation- related genes, including IL6, CCL3, and IFNL1, which were validated by qPCR. Additionally, Ribavirin demonstrated a certain inhibitory effect on the viral replication of both CVB5 and ECHO6 at a concentration of 50 µm. This study established a systematic comparison of the common transcriptomic differences and immune response characteristics of both CVB5 and ECHO6 infection in human cardiomyocytes. The marked upregulation of immune-related genes suggests that innate immunity and the inflammatory response play critical roles in cardiomyocytes defense against enterovirus infection. Ribavirin showed notable inhibitory activity against both CVB5 and ECHO6. The study sheds light on new insights into the foundations for the pathogenesis of enterovirus-associated VMC and the development of promising therapeutic approaches against VMC.
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