Richard P . Morrison , Jane Nishio , and Bruce Chesebro

Avian, murine, feline, and human retroviruses frequently cause immunosuppression in their respective hosts (1, 2). The mechanisms by which immune reactivity is impaired remain speculative. Virus infection often results in immune hyporeactivity, but in some instances inactivated virus causes suppression independently of cellular infection (3, 4). Thus, it appears likely that some viral proteins themselves can directly induce immunosuppression. The Friend murine leukemia virus complex (FV) l causes severe immunosuppression when inoculated into adult or newborn mice (1). FV complex, which is composed of a replication-competent helper virus (F-MuLV) and a repli~zationdefective spleen focus-forming virus (SFFV), causes a rapidly developing erythroleukemia in susceptible strains of adult mice. Early suppression of B lymphocyte immune functions and altered leukocyte migration have been reported (5-7). In some instances, cell-mediated immune functions are also diminished (8, 9). Kumar and Bennet (10) and Kumar et al. (11) developed a murine model for studying genetic resistance to FV-induced immunosuppression. They found that a non-H-2-1inked, autosomal gene, Fv-3, regulated susceptibility to in vitro and in vivo FV-induced immunosuppression, and proposed that Fv-3 acted by regulating the numbers or functions of suppressor T cells (I 2, 13). Several other mouse genes have been found to affect the course of FV-induced erythroleukemia (14-17 and Table I). In particular, two genes found within the MHC (H-2) influence spontaneous recovery from leukemia, probably by influencing development of virus-specific T cell-mediated immune responses (1618). The H-2 b/b genotype is associated with a high incidence of recovery compared to the H-2 a/b and H-2 "/a genotypes (17). In addition, a non-H-2-associated gene, Rfv-3, acts in a complementary fashion with H-2, and is required for recovery from leukemia (19). In the presence of a low-recovery H-2 genotype, H-2 a/b or H-2 a/a, the resistant Rfv-3 r/s genotype is associated with recovery from viremia and production of virus-specific antibodies that neutralize virus and lyse virus-infected cells in the presence of complement (19-21). Nevertheless, these mice die from progressive leukemia. Conversely, low-recovery BALB/c, A/WySn and A.BY mice, .which have the Rfv-3 s/s genotype fail to produce anti-FV