Evidence for immune-mediated destruction as mechanism for LCMV-induced anemia in persistently infected mice.

A docile substrain of lymphocytic choriomeningitis virus (LCMV) causes a persistent infection in adult C3HeB mice and induces a severe anemia, which, unlike the viremia, eventually resolves. Measurements of red blood cell (RBC) survival rates demonstrated an increased rate of RBC clearance in these animals, indicating a hemolytic process for the anemia. Normal clearance rates of RBCs from infected mice transfused into control mice suggested that there was not an intrinsic defect in these cells. It also appeared that RBC destruction was immune-mediated, as cyclophosphamide treatments prevented the onset of anemia in infected mice, whereas adoptive transfer (AT) of immune splenocytes into immunocompromised mice reestablished the condition. The AT experiments also demonstrated that the onset of anemia correlated with the functional state of the immune cells. In addition, opsonization of RBCs was demonstrated by macrophage phagocytosis, and the appearance of opsonized RBCs corresponded with the course of the anemia. These findings support a hypothesis of RBC opsonization and subsequent phagocytosis by macrophages of the reticuloendothelial system as the mechanism for RBC destruction in LCMV-induced hemolytic anemia.