Activity of the Keggin polyoxotungstate PM-19 against herpes simplex virus type 2 infection in immunosuppressed mice: role of peritoneal macrophage activation.

The in vivo antiviral activity of the Keggin polyoxotungstate PM-19 [K7(PTi2W10O40).6H2O] against herpes simplex virus type 2 (HSV-2) was investigated in mice immunosuppressed by cyclophosphamide (CY). When PM-19 was administered intraperitoneally to immunosuppressed mice for 3 days (once daily) starting at the time of infection, it prevented death due to HSV-2 encephalitis in a dose-dependent manner (10-25 mg/kg). The in vivo anti-HSV-2 activity of PM-19 was superior to that of acyclovir. Intraperitoneal administration of PM-19 to the immunosuppressed mice significantly increased the number of peritoneal cells, especially macrophages. PM-19 did not stimulate interferon-inducing activity or natural killer cell activity, but markedly enhanced peritoneal macrophage functions: (1) phagocytic activity as assessed by measuring the amount of 51Cr-labeled sheep red blood cells taken into the macrophages, and (2) extrinsic antiviral activity as monitored by reduction in the numbers of plaque formed upon cocultivation of HSV-2-infected HEL cells with the macrophages. These results point to the role of peritoneal macrophage activation in the activity of PM-19 against HSV-2 infection in immunosuppressed mice.