The Common Immune Responses Differences from Transcriptomic Profiling in Cardiomyocytes upon Coxsackievirus B5 and Echovirus 6 Infection

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.