Target Cell Heterogeneity in Murine Leukemia Virus Infection

Abstract

Abstract The susceptibility of mouse lymphocytes from various organs to infection by murine leukemia virus (MuLV) (Friend) was studied both in vivo and in vitro by using either Friend virus complex (FV) or lymphatic leukemic virus (LLV), the helper virus isolated from FV. Productively infected cells releasing infectious MuLV were identified as infectious centers (IC) on sarcoma+, leukemia- indicator fibroblasts. IC were detected by days 4 to 6 postinfection in spleen and bone marrow (BM); fewer IC were observed in lymph nodes (LN) and their appearance was delayed until day 8 in FV-infected mice and day 15 in LLV-infected mice. In both groups, the appearance of IC in LN correlated with the onset of splenomegaly (mean = 300 mg) and the development of infection in peripheral blood exceeding 1 × 106 focus-forming units/ml, suggesting that the IC observed in LN were due to dislodged, circulating infected spleen and BM cells rather than due to infection of LN cells. This possibility was tested directly by using a culture system whereby cells from spleen, BM, and LN from normal mice were infected with FV or LLV in vitro. The principal target for MuLV replication in the cultures appeared to be B lymphocytes because 1) stimulation with bacterial lipopolysaccharide (LPS) greatly enhanced the infection of unseparated BALB/c spleen and bone marrow cells, nylon wool-adherent BALB/c spleen cells, and spleen and BM cells from athymic (nude) mice, 2) pretreatment of spleen cells with a heterologous anti-mouse immunoglobulin antiserum plus complement reduced the infection, and 3) the majority of virus-permissive cells in BALB/c spleens were recovered in the pure population of Ig+ cells from an immunoadsorbent column. However, no IC were detectable in LPS-stimulated LN cells from either BALB/c or nude mice, confirming the fundamental difference in susceptibility to the MuLV component of FV between B cells from spleen, BM, and LN suggested by the in vivo studies.