Macrophage Extrinsic Antiviral Activity during Herpes Simplex Virus Infection

Abstract
Peritoneal macrophages from mice infected with herpes simplex virus type 2 (HSV-2) exhibited extrinsic antiviral resistance. When the macrophages were cocultivated in vitro with virus-infected cells the yield of virus was reduced markedly. Activity was not present 1-2 days p.i. [post-infection], peaked at 3-4 days, declined by 7 days and was absent at 14 days after HSV-2 infection. The extrinsic antiviral activity was limited to the adherent peritoneal macrophage population. The macrophage antiviral activity was also dose-dependent, with about 106 macrophages (macrophage:host cell ratio of about 2:1) reducing virus plaques > 90% and virus yield 1.5-3.0 log10. Comparable extrinsic antiviral activity was also exhibited by Corynebacterium parvum[Propionibacterium acnes]- or thioglycollate-elicited peritoneal macrophages. The macrophage activity was not species-specific, activity on Vero [African green monkey kidney] cells or syngeneic mouse embryo fibroblasts being comparable. Activity was also not virus-specific, as the active macrophages also inhibited vesicular stomatitis virus. The antiviral effects required viable macrophages; cell lysates did not inhibit virus growth.