RT Journal Article SR Electronic(1) A1 Shim, Seung-Hyun A1 Kim, Dae-Sun A1 Cho, Whajung A1 Nam, Jae-HwanYR 2014 T1 Coxsackievirus B3 regulates T-cell infiltration into the heart by lymphocyte function-associated antigen-1 activation via the cAMP/Rap1 axis JF Journal of General Virology, VO 95 IS 9 SP 2010 OP 2018 DO https://doi.org/10.1099/vir.0.065755-0 PB Microbiology Society, SN 1465-2099, AB Coxsackievirus B3 (CVB3) infection can trigger myocarditis and can ultimately lead to dilated cardiomyopathy. It is known that CVB3-induced T-cell infiltration into cardiac tissues is one of the pathological factors causing cardiomyocyte injury by inflammation. However, the underlying mechanism for this remains unclear. We investigated the mechanism of T-cell infiltration by two types of CVB3: the H3 WT strain and the YYFF attenuated strain. T-cell activation was confirmed by changes in the distribution of lymphocyte function-associated antigen-1 (LFA-1). Finally, we identified which viral gene was responsible for LFA-1 activation. CVB3 could infect and activate T-cells in vivo and in vitro, and activated T-cells were detected in CVB3-infected mouse hearts. LFA-1 expressed on the surface of these T-cells had been activated through the cAMP/Rap1 pathway. Recombinant lentiviruses expressing VP2 of CVB3 could also induce LFA-1 activation via an increase in cAMP, whilst VP2 of YYFF did not. These results indicated that CVB3 infection increased cAMP levels and then activated Rap1 in T-cells. In particular, VP2, among the CVB3 proteins, might be critical for this activation. This VP2–cAMP–Rap1–LFA-1 axis could be a potential therapeutic target for treating CVB3-induced myocarditis., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.065755-0