Alteration of Murine Mammary Tumor Metastasis and Growth by Cytomegalovirus Infection1

with CMV infections (21 , 26). These observations have been supported by studies from a number of laboratories utilizing a murine experimental model of acute CMV infection. Lympho cyte responses have been shown to be depressed to various Tand B-cell mitogens during the acute phase of MCMV infection (1, 10, 12, 28). Depression of other parameters of lymphocyte function has also been noted during MCMV infec tion, including mixed lymphocyte reaction (10), skin graft re jection (10), interferon production (12, 19), formation of he molytic antibody-forming spleen cells after sheep RBC injection into mice (18), and humoral antibody response to various antigens (11, 18, 19). The capacity of MCMV to affect host defense mechanisms adversely has been clearly demonstrated in a series of studies showing that viral, bacterial, and fungal infections may be potentiated during acute MCMV infection (4, 5, 19). While lymphocyte-mediated responses and resistance to secondary infections have been shown to be depressed by MCMV infection, there have been few studies defining the effect of MCMV on the macrophage. Although various lympho cyte functions are depressed, recent studies suggest that macrophage function may be enhanced duirng a MCMV infec tion (11, 27). Host resistance to the development of malignant tumors is a complex phenomenon which involves both lymphocyte (2, 6, 20) and macrophage functions (7, 8, 24). The capacity of CMV to modulate lymphocyte and reticuloendothelial cell functions, as well as to persist in the host in a latent form and to be reactivated at a later date, led us to postulétethat infection with CMV may alter the resistance of the host to the development of malignant tumors. In order to test this hypothesis, we utilized the muninemodel developed by Hill and Bush (9). The effect of MCMV infection on the establishment and growth of pulmonary tumor nodules was determined in animals inoculated i.v. with a single-cell suspension of muninemammary tumor cells.