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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.
Insights
Early murine cytomegalovirus (MCMV) replication in the spleen, primarily within macrophages, significantly worsens liver injury and lethal disease outcomes. Splenectomy improves survival rates and reduces liver viral load.
Area of Science:
- Virology
- Immunology
- Pathogenesis
Background:
- Acute lethal murine cytomegalovirus (MCMV) infection primarily targets the spleen and liver for early viral replication.
- High viral titers are observed in these organs within 96 hours of inoculation.
Purpose of the Study:
- To investigate the impact of early splenic viral replication on the pathogenesis of MCMV infection.
- To determine the cellular sites of MCMV replication within the spleen.
Main Methods:
- Splenectomy was performed on mice to assess its effect on survival and viral load.
- Viral titers in the spleen and liver were quantified.
- Electron microscopy was used to identify the primary site of viral replication in splenic macrophages.
Main Results:
- Splenectomized mice exhibited significantly higher survival rates compared to control groups.
- Hepatic viral titers were substantially lower in splenectomized mice.
- Macrophages were identified as the predominant site of MCMV replication in the spleen.
Conclusions:
- Early MCMV replication in splenic macrophages exacerbates virus-induced hepatic injury.
- Splenic viral replication contributes significantly to the pathogenesis of lethal MCMV infection.