Roles of macrophages in measles virus infection of genetically modified mice

Knowledge of the mechanisms of virus dissemination in acute measles is curs ory, but cells of the monocyte/macrophage (MM) lineage appear to be early t argets. We characterized the dissemination of the Edmonston B vaccine strai n of measles virus (MV-Ed) in peripheral blood mononuclear cells (PBMC) of two mouse strains expressing the human MV-Ed receptor CD46 with human-like tissue specificity and efficiency, In one strain the alpha/beta interferon receptor is defective, allowing for efficient MV-Ed systemic spread. In bot h mouse strains the PBMC most efficiently infected were F4/80-positive MMs, regardless of the inoculation route used. Circulating B lymphocytes and CD 4-positive T lymphocytes were infected at lower levels, but no infected CDS -positive T lymphocytes were detected. To elucidate the roles of MMs in inf ection, we depleted these cells by clodronate liposome treatment in vivo. M V-Ed infection of splenic MM-depleted mice caused strong activation and inf ection of splenic dendritic cells (DC), followed by enhanced virus replicat ion in the spleen. Similarly, depletion of lung macrophages resulted in str ong activation and infection of lung DC. Thus, in MV infections of genetica lly modified mice, blood monocytes and tissue macrophages provide functions beneficial for both the virus and the host: they support virus replication early after infection, but they also contribute to protecting other immune cells from infection. Human MM may have similar roles in acute measles.