Journal
ANTIVIRAL RESEARCH
Volume 217, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.antiviral.2023.105702
Keywords
Coxsackievirus B3; Viral myocarditis; miR-19a/19b; RdRp; Viral genomic RNA stability
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This study found that miR-19a and miR-19b were significantly up-regulated in heart tissues of CVB3-infected mice, and they facilitated viral biosynthesis and replication by targeting the encoding region of RdRp. Treatment with miR-19b antagomir suppressed CVB3 replication and infection in cells and reduced the cardiac viral load of CVB3-infected mice, resulting in alleviation of myocarditis.
Coxsackievirus B3 (CVB3) is one of the major pathogens of viral myocarditis, lacking specific anti-virus therapeutic options. Increasing evidence has shown an important involvement of the miR-17-92 cluster both in virus infection and cardiovascular development and diseases, while its role in CVB3-induced viral myocarditis remains unclear. In this study, we found that miR-19a and miR-19b were significantly up-regulated in heart tissues of CVB3-infected mice and exerted a significant facilitatory impact on CVB3 biosynthesis and replication, with a more pronounced effect observed in miR-19b, by targeting the encoding region of viral RNA-dependent RNA polymerase 3D (RdRp, 3Dpol) to increase viral genomic RNA stability. The virus-promoting effects were nullified by the synonymous mutations in the viral 3Dpol-encoding region, which corresponded to the seed sequence shared by miR-19a and miR-19b. In parallel, treatment with miR-19b antagomir not only resulted in a noteworthy suppression of CVB3 replication and infection in infected cells, but also demonstrated a significant reduction in the cardiac viral load of CVB3-infected mice, resulting in a considerable alleviation of myocarditis. Collectively, our study showed that CVB3-induced cardiac miR-19a/19b contributed to viral myocarditis via facilitating virus biosynthesis and replication, and targeting miR-19a/19b might represent a novel therapeutic target for CVB3-induced viral myocarditis.
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