Arch Virol (1993) 131:265-275 _Archives ....... Vi rology © Springer-Verlag I993 Printed in Austria A low oneogenic variant of friend murine leukemia virus with strong immunosuppressive properties Arild Faxvaag ~, H. Y. Dai 2, H. Aarseth 3, and A. B. Dalen 4 1 Institute of Cancer Research, University of Trondheim, 2Unigen, University of Trondheim, Medisinsk Teknisk Senter, Trondheim, 3Department of Pathology, Trondheim Regional Hospital, Trondheim 4Department of Microbiology, Trondheim Regional Hospital, Trondheim, Norway Accepted February 25, 1993 Summary. Friend leukemia complex (FLC) is known to induce immunosuppres- sion but the use of FLC in studies of immune cells function is disadvantageous since the immunosuppression always is accompanied by an acute erythroleu- kemia. To obtain immunosuppressive variants of FLC with reduced leuke- mogenic potential, we isolated T-helper cells from FLC infected mice, and passed lysates of the cells to recipient uninfected mice. A group of these mice developed a condition distinct from the disease induced by FLC. A viral stock prepared from these mice, designated Fd-MIV for friend derived murine immunodefiency virus, induced a profound suppression of the primary antibody response without acute transformation in adult NMRI mice. Terminally a wasting disease with weight loss, atrophy of the thymus and lymph nodes and renal disease was observed in some mice. Analysis of viral DNA and RNA from infected NIH 3T3 cells showed that Fd-MIV contained at least two viral components, a 8.4 kb friend murine leukemia virus (F-MuLV) and a 7.4 kb mink cell focus (MCF) / xenotropic virus related genome. The 7.4 kb genome was not detected in Fd- MIV infected, immunocompromised mice indicating that the 8.4 kb genome might be responsible for the disease. Introduction Friend leukemia complex (FLC), which consists of a mixture of the defective spleen focus-forming virus (SFFV) and the helper virus, friend murine leukemia virus (F-MuLV) [9, 24], induces acute erythroleukemia and immunosuppression in susceptible mice. In FLC infected mice, the function of both lymphocytes and monocytes is suppressed I-2, 8, 10--12, t4, 15], and due to these properties FLC has been suggested as a murine model for AIDS [22]. However, the use