The objective of the proposed research is to investigate host resistance to viral infections and factors which may affect host defense mechanisms. (A) The nature of the cellular response to viral infections will be determined in an experimental animal model (mouse) utilizing a subcutaneous pocket. The kinetics and type of cell response to the implantation of viruses or virus-infected cells will be defined with emphasis on cell-mediated immunity, macrophage function and interferon production. (B) The capacity of macrophages to recognize surface changes in virus infected cells and inhibit virus replication will be investigated. The mechanism of virus inhibition by macrophages will be elucidated in several tissue culture systems (Herpesvirus hominis, cytomegalovirus, vaccinia, and Newcastle disease virus in mouse embryo fibroblast cultures). (C) The effect of immunopotentiation (non-specific stimulation) by Corynebacterium acnes, C. parvum and BCG on viral infections in vivo will be delineated. Utilizing the experimental models described above (in sections A & B) the mechanism of altered host resistance will be determined. (D) Finally, the capacity of murine cytomegalovirus to suppress host resistance to staphylococcal, pseudomonas and monilial infections will be further defined and the mechanism of altered host resistance, specifically the effect of virus on phagocytosis and chemotaxis of peripheral white blood cells, as well as on the cellular elements of the bone marrow will be elucidated. BIBLIOGRAPHIC REFERENCES: Kern, E.R., Richards, J.T., Overall, J.C., Jr., and Glasgow, L.A. Genital Herpesvirus hominis infection of mice. II. Treatment with phosphonoacetic acid, adenine arabinoside and adenine arabinoside 5' monophosphate. J. Infect. Dis. 135: 557-567, 1977. Glasgow, L.A., Fischbach, J., Bryant, S.M., and Kern, E.R. Immunomodulation of host resistance to experimental viral infections in mice: Effect of corynebacterium acnes, corynebacterium parvum and BCG. J. Infect. Dis. 135: May 1977.