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 activate the alternative and classical pathway of complement. CVB3 proteins interact with complement component 3 (C3, a soluble protein effector of innate immunity) after either in vitro exposure to mouse serum or in vivo murine infection and activate the alternative pathway of complement. In addition, we demonstrate that viral antigen retention and localization in germinal centers is dependent on C3, while virus antigen retention in extrafollicular regions in the spleen is not. In vivo depletion of native C3 abolished the rapid formation of virus-specific germinal centers (by day 3 post-CVB3 infection) in the absence of serum anti-CVB3 antibodies. These studies demonstrate that innate immune mechanisms, such as C3 interaction with CVB3, are essential for splenic antiviral germinal center formation in naive (antigen nonsensitized) mice resistant (C57BL/6J strain) and susceptible (A/J strain) to CVB3-induced myocarditis.
Anderson
D R
DR
Department of Pathology, University of British Columbia, Vancouver, Canada.
Carthy
C M
CM
Wilson
J E
JE
Yang
D
D
Devine
D V
DV
McManus
B M
BM
D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D002213:Capsid / Q000378:metabolism*; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D029822:Enterovirus B, Human / Q000378:metabolism*; D018858:Germinal Center / Q000276:immunology; D006461:Hemolysis; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000276:immunology / Q000821:virology*; D011485:Protein Binding; D012367:RNA, Viral / Q000032:analysis; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000821:virology; D013997:Time Factors
D000956:Antigens, Viral; D003176:Complement C3; D012367:RNA, Viral