Properties of mouse leukemia viruses XVIII. Effective treatment of AKR leukemia with antibody to gp7l eliminates the neonatal burst of ecotropic AKR virus producing cells

Abstract

To suppress spontaneous leukemia, treatment of AKR mice with antibody to the murine leukemia virus (MuLV) major glycoprotein (gp71) must commence during a narrow “window” period between birth and Day 3. To examine the effect of treatment on virus expression, infectious MuLV cell centers (ICCs), free MuLV, and viral antigen presence were examined in various organs of control and antibody-treated neonatal AKR mice. Ecotropic MuLV ICCs and viral antigens were found to increase 100-fold between Days 3 and 8 in thymuses, spleens, and livers in untreated mice. Quantitatively, spleens and livers had about 100-fold more viral ICCs than the thymus. After Day 8 viral ICCs persisted at plateau levels in all organs, with thymic ICCs 100-fold below spleens and livers. Maximal plateau levels of free ecotropic virus were reached only by Day 16. Xenotropic MuLV was occasionally isolated in ICC assays, but no recombinant MuLV was ever detected in any organ early in life. Viral p30 and gp7l antigen expression detected by immunofluorescent assays (IFA) closely corresponded to ICCs. In contrast, in AKR mice treated three or more times with gp7l antibody, MuLV ICCs were essentially undetectable during the first 3 weeks of life. In IFA, anti-gp7l-treated mice also had no virus antigen-positive cells in the organs tested. Spleen cells from control antibody-treated AKR mice were also treated in vitro with immune antibody and tested for virus- and antigen-positive cells. Anti-gp7l antibody did bind in vitro to virus-positive cells as measured by IFA but was neither cytotoxic nor reduced viral ICCs. However, the addition of complement to anti-gp7l antibody-coated cells resulted in a highly specific, effective killing of those cells scoring as viral ICCs. To determine the role of induction and/or clonal expansion of virus-positive cells relative to virus spread, perinatal F 1 (NIH × AKR) (by convention, maternal parent listed first in F 1 designations) and (BALB/c × AKR) mouse cells were assayed for ecotropic ICCs. Fv-1 n permissive (NIH × AKR) mice had only slightly fewer ICCs, and the timing and distribution of virus release was similar to AKR mice. Fv-1 nb restrictive (BALB/c × AKR) mice had different kinetics of ICC formation. At plateau, the ICCs were severalfold lower than that in Fv-1 n permissive mice, suggesting that an increase of virus-positive cells occurs during the neonatal period by means other than virus spread. However, virus spread may account for up to a 10-fold-increase in ICCs in AKR mice. The above data graphically demonstrated that the treatment “window” corresponded to a time just prior to the burst of ecotropic virus ICCs. The nature of ecotropic virus-positive cells and their elimination with treatment are discussed relative to later events in AKR leukemogenesis.