Genetic resistance to Friend virus-induced erythroleukemia and immunosuppression.

Abstract

The Friend virus (FV) is a complex of a replication-defective spleen focus forming virus (SFFV) and its helper lymphatic leukemia virus (LLV) (Steeves et al. 1971; Troxler et al. 1977). Infection of susceptible adult mice with FV leads to a rapidly developing erythroleukemia accompanied by extensive viral replication in the spleen and profound suppression of humoral and cellular immunity (Bennett and Steeves 1970; Mortensen et al. 1974). Within 7–9 days after infection with small doses of FV, the spleen becomes enlarged due mainly to focal proliferation of neoplastic erythroid cells. This results in the characteristic appearance of raised yellowish foci when such spleens are fixed in Bouin’s solution (Axelrad and Steeves 1964). As the disease progresses, both liver and spleen enlarge, but thymus and lymph nodes remain relatively unaffected. One variant of FV, isolated initially by Mirand (Mirand et al. 1968), leads to a progressive increase in hematocrit (polycythemia), and eventually most mice die, often with splenic rupture, in 30–60 days. Several H-2-linked and nonlinked genes which regulate the effects of FV have been described. The Fv-1 locus controls host resistance to the helper virus, Fv-1-mediated resistance is not unique to Friend LLV but rather a general phenomenon seen with respect to a variety of murine leukemia virus (MuLV) isolates (Pincus et al. 1971). Two alleles designated as Fv-1 n and Fv-1 b have been described and these define the N or B tropism of MuLV. The Fv-1 gene regulates viral replication, and it is possible to overcome Fv-1 resistance by utilizing laboratory-derived NB-tropic viruses.