Contribution of macrophage arginase in the intrinsic restriction of herpes simplex virus replication in permissive macrophage cultures induced by gamma-interferon containing products of activated spleen cells.

Cultured peritoneal macrophages (PM) from adult mice of strain DBA/2 (but not C57BL/6) supported productive replication of HSV, as monitored by infectious virus yield and electron microscopy. In contrast, PM of DBA/2 origin, when pretreated with supernatants of Con A-stimulated spleen cells containing immune interferon (IFN-gamma) activity, manifested remarkable intrinsic restriction to HSV replication. The acquisition of this intrinsic restriction to virus replication correlated with the generation of appreciably elevated levels of arginase in supernate of treated PM. Addition of incremental doses of exogenous arginine in the culture medium led to the abrogation of induced restriction to HSV replication in DBA/2 PM, indicating the critical role of arginase in the phenomenon. Furthermore, anti-HSV activity of arginase levels released into the culture medium of IFN containing supernate-treated PM became apparent when assayed on PM, which were precultured in arginine-deficient medium for 24 hours before virus infection and exposure to arginase containing preparation. Taken together, these observations indicate that macrophage arginase can mediate intrinsic restriction to HSV replication in PM.