The purpose of the studies outlined in this proposal is to utilize a clearly defined animal model for human CMV infection in an attempt to learn which parameters of lymphocyte, neutrophil, and macrophage function are either adversely or otherwise affected by maternal CMV infections. The effects of prophylactic and therapeutic intervention in altering the function of these cells will be determined. Results should also be applicable to understanding these phenomena in other patient populations. This proposal represents a logical extension of ongoing studies of CMV infections in our laboratory. Initial experiments will delineate the effects of acute maternal CMV infections on the mobilization and function of neutrophils, macrophages and lymphocytes as a result of primary virulent CMV infection or CMV reactivation during pregnancy. Following these initial investigations we will examine the effects which various forms of maternal CMV immunity may have in altering the effects of virulent CMV infection on immune function in progeny. These include prior maternal vaccination with live CMV vaccine or envelope antigen vaccines, areas in which the guinea pig CMV model has already proven useful for investigations of vaccine efficacy. Our laboratory is currently producing guinea pig interferon which will be available for treatment of primary CMV infections during pregnancy. This will allow the evaluation of CMV pathogenesis in pregnant animals during treatment with interferon and alterations in the incidence of fetal infection, stillbirths, and abortions. The third part of this study will investigate the use of interferon for therapy of perinatal CMV infections. There are advantages to this approach, first, an appropriate animal model allows control of many variables such as the degree of viral infection. Second, it will be possible to determine cellular functions at defined times during CMV infection. Third, the guinea pig model of human CMV infection has been examined extensively our laboratories. It represents a well accepted model for study of both CMV pathogenesis, lymphocyte, and phagocytic cell function.
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