Intracellular mechanisms of innate resistance to vaccinia virus.

Abstract

Previous studies have demonstrated that mouse peritoneal macrophages restrict vaccinia virus replication in vitro, whereas rabbit peritoneal macrophages are susceptible. Previous autoradiography experiments revealed that no significant viral DNA synthesis appeared in mouse macrophages, indicating that an abortive infection had occurred which blocked viral replication prior to DNA synthesis. In an attempt to define the nature of this restriction, an analysis of the virus infectious cycle was undertaken. Electron micrographs revealed that adsorption, first stage of uncoating, and second stage of uncoating were identical in both mouse and rabbit macrophages. Assembly of viral components was detected in rabbit macrophages but not in mouse macrophages. Biochemical studies revealed no thymidine phosphorylating activity in mouse macrophages indicating that the block in the virus replicative cycle occurred at the narrow margin between the second stage of uncoating and viral DNA synthesis. These data support our hypothesis that normal mouse peritoneal macrophages contribute to specific, non-interferon mediated resistance to vaccinia virus by aborting the infection at some early stage of the replicative cycle.