Coxsackievirus B3 regulates T cell infiltration by LFA-1 modification through Rap1 activation (P5075)

Abstract

Abstract Coxsackievirus B3 (CVB3) infection has the potential to induce myocarditis. The following may be the mechanisms of CVB3-induced pathogenesis: viral infection directly causes injuries to cardiomyocytes through viral cytopathic effect and virus-activated T cell infiltration indirectly causes injuries to cardiomyocytes through inflammation. However, the detailed mechanism of T cell infiltration remains unknown. The present study observed that infiltrated T cells could be detected in the hearts of CVB3-infected mice. Meanwhile, attenuated CVB3 (YYFF) did not elicit T cell infiltration in infected mouse hearts. Rap-1, Ras family of small GTPases, is a critical regulator of T cell activation. CVB3 infection was found to activate Rap1 through cAMP induction. The downstream molecules of Rap1, ERK and p-CREB, which are involved in T cell activation and differentiation, were also activated after CVB3 infection. However, this result did not occur in the case of YYFF. This Rap-1 activation leads to an active form of LFA-1 on T cells that can be bound to intracellular adhesion molecule-1 (ICAM-1) on myocytes for T cell infiltration after CVB3 infection. This mechanism of CVB3-induced T cell infiltration may contribute to be a potential therapeutic agent for virus-induced myocarditis. Keywords: Coxsackievirus B3, YYFF, LFA-1