Host defense mechanisms against viruses and virus-infected cells consist of highly complex and incompletely understood interactions between cellular and humoral elements. Studies carried out in the previous years of this grant have shown that many human pathogen viruses and cells infected with these viruses directly activate the classical or alternative complement (C) pathways; specific antibody (Ab) when present augments C triggering. As a consequence of these activation reactions, the viruses and virus-infected cells become coated with large numbers of molecules of C, often together with Ab; such viruses and virus-infected cells are likely also thus coated in vivo. C and Ab coated viruses may interact with complement receptors (CR) and/or Fc receptors rather than the physiologic virus receptor and such interactions with the """"""""wrong receptor"""""""", now demonstrated for several viruses may alter pathobiological consequences. In earlier years we characterized the molecular aspects involved in such C triggering reactions with a number of viruses and infected cells, in the present project we seek to determine the biological significance and importance of these reactions. It is our hypothesis that the coating of pathogen viruses and cells infected with such viruses with C and/or Ab as a physiologic defense mechanism facilitate viral destruction and likely also augmenting specific antiviral immunity. In our studies, we shall focus on Epstein-Barr virus (EBV), a human herpesvirus which is also a candidate human cancer virus, as it is oncogenic in subhuman primates, transforms human cells in vitro, causes a human lymphoproliferative disorder and is strongly associated with two human malignancies. In other studies we shall explore the role of idiotypic-antiidiotypic interactions in the EBV system. Such interactions are important in the regulation of antiviral and other immune responses and may be particularly instructive with EBV which alters immune function and is involved in multiple diseases with altered immunoregulation.
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