The objective of this proposal is to explore the hypothesis that antiviral antibodies play an important role in the pathogenesis of congenital and perinatal human cytomegalovirus (CMV) infections. In the first section of this proposal, immunogenic, CMV-encoded proteins will be more fully characterized by a variety of immunologic and biochemical techniques. Included in these studies will be expression of genes encoding specific proteins in prokaryotic vectors. These recombinant proteins will be used to define structural and functional domains of CMV envelope proteins. The findings of these studies will then be used in the second part of the proposal which will comprehensively define the antiviral antibody response in terms of the magnitude, antigen specificity, isotype and IgG subclass distribution and kinetics in sequentially collected specimens from populations of well characterized patients. These investigations will utilize selected patient populations such that the antiviral antibody response to CMV can be correlated with the prevention of intrauterine and breast milk transmission and modulation of the virulence of the ensuing infection. From these studies we should gain a greater understanding of the role of antiviral antibodies in the pathogenesis of congenital and perinatal CMV infection. In addition, our findings should identify serologic markers associated with transmission and virulence of CMV infections which could potentially be of use in the diagnosis and treatment of these infections.
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