The immunosuppressive drug cyclophosphamide was used to study the effect of immunosuppression on the degree of chronic lactic dehydrogenase virus (LDV) viremia in mice. Weekly injections of cyclophosphamide caused an increase of LDV viremia of ca. 2.5 logio 50% infectious doses per ml as compared to the viremia in the nontreated mice. This increase occurred at about the same time that the formation of antibody with a neutralization index of 2 to 3 logio per ml could be demonstrated in the serum of control mice, whereas both neutralizing antibody and sensitized (antibody-bound but infectious) virus were absent in the immunosuppressed mice. In one experiment, antibody did not reappear 28 weeks after a 24-week course of cyclophosphamide treatment. In another experiment in which the drug was given for 12 weeks, antibody appeared again in the treated mice 14 weeks after cessation of drug administration and was accompanied by a decrease in viremia. The normal decrease of early viremia during the first 2 weeks of infection in immunosuppressed mice suggests that the immune response is not the cause of this initial decrease in LDV viremia but that interferon and perhaps other nonimmune factors may be involved here. The increased viremia in the immunosuppressed mice during the later stages of infection indicates that the immune response plays an important role in partial control of chronic viremia. The quantitative correlation between the decrease in neutralizing antibody and the increase in viremia in immunosuppressed mice suggests that antibody rather than cellular immunity may be the more important immune factor in the control of chronic viremia.Mice infected with lactic dehydrogenase virus (LDV; reference 17) present a useful model for a study of the role of immune and nonimmune factors in controlling viremia in a chronic viral infection. The viremia in LDV-infected mice lasts for the lifetime of the mice without any overt pathology (14). Serum interferon can be detected during the first few days of infection (3, 7, 10), and neutralizing antibody can be detected after a few weeks (15, 19); however, the relative roles of interferon and antibody, as well as that of cellular immunity, in determining the level of viremia in this infection remain unclear.In an attempt to clarify the importance of immune processes in this chronic infection, we have studied the effect of a potent immunosuppressive agent, cyclophosphamide, on viremia and on the formation of neutralizing antibody and sensitized virus in LDV-infected mice.
MATERIALS AND METHODSAnimals. Random bred Swiss albino (15 to 20 g, female) mice were supplied by the animal production section of the National Institutes of Health.Virus. The strain of LDV used was isolated from a naturally infected Ehrlich ascites carcinoma carried in CDF, mice (7). Stock LDV was obtained from LDVfree Ehrlich ascites tumor-bearing mice, which were infected intraperitoneally with 107°50.% infectious doses (ID50) per mouse 6 to 8 days after tumor implantation. Twenty-four hours after infection...