COMPLEMENT COMPONENT-3 INTERACTIONS WITH COXSACKIEVIRUS B3 CAPSID PROTEINS - INNATE IMMUNITY AND THE RAPID FORMATION OF SPLENIC ANTIVIRAL GERMINAL-CENTERS

Innate immunity is central to the clearance of pathogens from hosts as well as to the definition of acquired immune responses (D. T. Fearon, and R. M. Locksley, Science 272:50-53, 1996). Coxsackievirus B3 (CVB3 ), a human cardiopathic virus, was evaluated for the ability to activa te the alternative and classical pathway of complement, CVB3 proteins interact with complement component 3 (C3, a soluble protein effector o f innate immunity) after either in vitro exposure to mouse serum or in vivo murine infection and activate the alternative pathway of complem ent. In addition, we demonstrate that viral antigen retention and loca lization in germinal centers is dependent on C3, while virus antigen r etention in extrafollicular regions in the spleen is not. In vivo depl etion of native C3 abolished the rapid formation of virus-specific ger minal centers (by day 3 post-CVB3 infection) in the absence of serum a nti-CVB3 antibodies, These studies demonstrate that innate immune mech anisms, such as C3 interaction with CVB3, are essential for splenic an tiviral germinal center formation in naive (antigen nonsensitized) mic e resistant (C57BL/6J strain) and susceptible (A/J strain) to CVB3-ind uced myocarditis.