Key result
Coxsackievirus B3 infection drives stage-specific gene co-expression modules in acute versus chronic myocarditis.
Why the study?
Despite extensive research into myocarditis pathogenesis, effective treatments remain elusive, prompting exploration of the potential pathogenesis and hub genes for viral myocarditis.
Identification of stage-specific gene co-expression networks and hub genes provides novel insights into the molecular pathogenesis of acute and chronic viral myocarditis.
Stage-specific modules in murine viral myocarditis remain hypothesis-generating; leaves open human validation and therapeutic targeting.
BACKGROUND: Myocarditis is an inflammatory myocardial disease, which may lead to heart failure and sudden death. Despite extensive research into the pathogenesis of myocarditis, effective treatments for this condition remain elusive. This study aimed to explore the potential pathogenesis and hub genes for viral myocarditis. METHODS: A weighted gene co-expression network analysis (WGCNA) was performed based on the gene expression profiles derived from mouse models at different stages of viral myocarditis (GSE35182). Functional annotation was executed within the key modules. Potential hub genes were predicted based on the intramodular connectivity (IC). Finally, potential microRNAs that regulate gene expression were predicted by miRNet analysis. RESULTS: Three gene co-expression modules showed the strongest correlation with the acute or chronic disease stage. A significant positive correlation was detected between the acute disease stage and the turquoise module, the genes of which were mainly enriched in antiviral response and immune-inflammatory activation. Furthermore, a significant positive correlation and a negative correlation were identified between the chronic disease stage and the brown and yellow modules, respectively. These modules were mainly associated with the cytoskeleton, phosphorylation, cellular catabolic process, and autophagy. Subsequently, we predicted the underlying hub genes and microRNAs in the three modules. CONCLUSIONS: This study revealed the main biological processes in different stages of viral myocarditis and predicted hub genes in both the acute and chronic disease stages. Our results may be helpful for developing new therapeutic targets for viral myocarditis in future research.
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Ma et al. (2020) studied Viral myocarditis (n=18). Coxsackievirus B3 infection vs. PBS injection (normal group) was evaluated on Gene co-expression modules correlated with acute or chronic disease stages. Coxsackievirus B3 infection in mice induced stage-specific gene co-expression changes, with the turquoise module strongly correlating with acute myocarditis (r=0.9, p=5x10^-7) and the brown and yellow modules correlating with chronic disease.
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