The pathogenesis of Vaccinia virus toxicity. II. An electron microscopic study

The intravenous injection of mice with toxic doses of vaccinia virus, prepared in the Ehrlich ascites carcinoma, usually produces fatal intravascular coagulation, within 24 hours. Light and electron microscope studies demonstrate occlusion of the microcirculation of lungs and livers by fibrin. Fibrin deposition appears to be prevented in mice injected with heparinized virus preparations. However, in lieu of fibrin deposition, within the microcirculation widespread intravascular platelet aggregation occurs. Platelets within these aggregates are in various stages of degranulation, and some platelets have phagocytosed vaccinia virus. Platelet aggregation was not observed in mice receiving injections of heparinized material prepared from uninfected tumors. In mice surviving longer than 12 hours, hepatocytes and endothelial cells of pulmonary capillaries are the sites of viral replication. Although many hepatocytes are infected in mice surviving longer than 12 hours, it is postulated that hepatocyte necrosis is in part due to the congestive effects resulting from obstruction of liver and pulmonary capillaries. These studies suggest that vaccinia virus may trigger in vivo platelet aggregation, and that obstruction of the lung and liver microcirculation by these aggregates is the initial lesion of vaccinia virus toxicity.