PATHOGENESIS OF MURINE ENTEROVIRUS MYOCARDITIS - VIRUS DISSEMINATION AND IMMUNE CELL TARGETS

In order to identify organ and cellular targets of persistent enterovi rus infection in vivo, immunocompetent mice (SWR/J, H-2(q)) were inocu lated intraperitoneally with coxsackievirus B3 (CVB3). By use of in si tu hybridization for the detection of enteroviral RNA, we show that CV B3 is capable of inducing a multiorgan disease. During acute infection , viral RNA was visualized at high levels in the heart muscle, pancrea s, spleen, and lymph nodes and at comparably low levels in the central nervous system, thymus, lung, and liver. At later stages of the disea se, the presence of enteroviral RNA was found to be restricted to the myocardium, spleen, and lymph nodes, To characterize infected lymphoid cells during the course of the disease, enteroviral RNA and cell-spec ific surface antigens were visualized simultaneously in situ in spleen tissue sections, In acute infection, the majority of infected spleen cells, which are located primarily at the periphery of lymph follicles , were found to express the CD4R/B220(+) phenotype of pre-B and B cell s. Whereas viral RNA was also detected in certain CD4(+) helper T cell s and Mac-1(+) macrophages, no enteroviral genomes were identified in CD8(+) cytotoxic/suppressor T cells. fates in disease, the localizatio n of enteroviral RNA revealed a persistent type of infection off B cel ls within the germinal centers of secondary follicles. In addition, de tection of the replicative viral minus-strand RNA intermediate provide d evidence for virus replication in lymphoid cells of the spleen durin g the course of the disease, These data indicate. that immune cells ar e important targets of CVB3 infection, providing a noncardiac reservoi r for viral RNA during acute and persistent myocardial enterovirus inf ection.