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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Experimental Virology Study Section (EVR)
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Scripps Research Institute
San Diego
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Cooper, N R; Nowlin, D; Taylor, H P et al. (1991) Cellular receptor for human cytomegalovirus. Transplant Proc 23:56-9, discussion 59
Norris, K A; Bradt, B; Cooper, N R et al. (1991) Characterization of a Trypanosoma cruzi C3 binding protein with functional and genetic similarities to the human complement regulatory protein, decay-accelerating factor. J Immunol 147:2240-7
Cooper, N R; Bradt, B M; Rhim, J S et al. (1990) CR2 complement receptor. J Invest Dermatol 94:112S-117S
Taylor, H P; Cooper, N R (1990) The human cytomegalovirus receptor on fibroblasts is a 30-kilodalton membrane protein. J Virol 64:2484-90
Nemerow, G R; Mullen 3rd, J J; Dickson, P W et al. (1990) Soluble recombinant CR2 (CD21) inhibits Epstein-Barr virus infection. J Virol 64:1348-52
Cannon, M J; Pisa, P; Fox, R I et al. (1990) Epstein-Barr virus induces aggressive lymphoproliferative disorders of human B cell origin in SCID/hu chimeric mice. J Clin Invest 85:1333-7
Nemerow, G R; Moore, M D; Cooper, N R (1990) Structure and function of the B-lymphocyte Epstein-Barr virus/C3d receptor. Adv Cancer Res 54:273-300
Moore, M D; DiScipio, R G; Cooper, N R et al. (1989) Hydrodynamic, electron microscopic, and ligand-binding analysis of the Epstein-Barr virus/C3dg receptor (CR2). J Biol Chem 264:20576-82
Taylor, H P; Cooper, N R (1989) Human cytomegalovirus binding to fibroblasts is receptor mediated. J Virol 63:3991-8
Cooper, N R; Nemerow, G R (1989) Complement and infectious agents: a tale of disguise and deception. Complement Inflamm 6:249-58

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