Lethal infection with murine cytomegalovirus after early viral replication in the spleen

Abstract

In acute lethal murine cytomegalovirus (MCMV) infection the spleen and liver are the principal sites of early viral replication. MCMV titers increase rapidly in the spleen and liver, exceeding 10(6) and 10(5) plaque-forming units (pfu)/g of tissue, respectively, within 96 hr of viral inoculation. Experiments were performed to determine the impact of early splenic viral replication on disease pathogenesis. Splenectomized mice survived acute infection in significantly greater numbers (25 of 34 vs 14 of 33, respectively) than controls and had lower hepatic viral titers (1.9 X 10(4) vs 2.4 X 10(5) pfu/g, respectively). Examination of the spleen by electron microscopy after administration of phagocytic markers demonstrated that macrophages were the predominant site of viral replication. It is concluded that early replication of MCMV in splenic macrophages augments virus-induced hepatic injury and thus contributes to the pathogenesis of lethal MCMV infection.