Host defense mechanisms against viruses and virus infected cells consist of highly complex and incompletely understood interactions between cellular and humoral elements. This proposal focuses on interactions of the humoral immune system, primarily complement (C), with human pathogen viruses and with virus infected human cells. C is a major biological mediator in man, able to produce inflammation and to mediate the opsonic, phagocytic, or lytic destruction of certain viruses and virus infected cells. This proposal examines the possibility that C functions as a natural defense mechanism operative against viruses and virus infected cells prior to antibody formation. The interactions of highly purified components of the C system with isolated Epstein-Barr Virus (EBV) and with human cells infected with EBV will be examined. EBV is 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. For comparison, interactions of C with another virus, influenza, and with human cells infected with influenza, measles, and an RNA tumor virus (retrovirus) will also be studied. A basic molecular and mechanistic approach will be employed. The emphasis will thus be on the structural features of the virus of infected cell which trigger the C components and on the nature and mechanism of the activation reactions. The biological consequences to the virus and the infected cell of these interactions will be analyzed and the precise manner in which the viruses and virus infected cells are neutralized or destroyed will be determined.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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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
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
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
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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