Histone deacetylase inhibitors suppress coxsackievirus B3 growth in vitro and myocarditis induced in mice.

UNLABELLED: Clinical importance of myocarditis, predominantly caused by coxsackievirus B3 (CVB3), is recently rising. However, a detailed mechanism of pathogenesis of CVB3 myocarditis still needs to be clarified. Recently, it has been reported that histone modifications including acetylation are involved in coxsackievirus replication. To examine whether the CVB3 replication requires histone acetylation, histone deacetylase (HDAC) inhibitors were employed. We found that the HDAC2 activity increased in virus-infected cells at 12 hrs p.i. and that HDAC inhibitors suppressed the virus replication in vitro. This suggests that the HDAC2 activity may be required for the virus replication. Eventually, a HDAC inhibitor trichostatin A protected against CVB3-induced myocardial injury in vivo. Our results suggest that HDAC may be a novel therapeutic target for treating viral myocarditis. KEYWORDS: coxsackievirus B3; histone acetyltransferase; histone deacetylase; HDAC inhibitors, trichostatin A; apicidin; valproic acid; shRNA; myocarditis; mouse.