FIG. 6.

Schematic diagram of the vaccinia virus multiplication cycle including sites of action of poxvirus-encoded antagonists of the IFN response. The enveloped vaccinia virion particle has a large linear dsDNA genome. Virus penetration probably involves fusion between the viral envelope and cellular membranes, with release of the subviral core particle into the cytoplasm, where virus replication occurs. Early viral mRNAs synthesized by the virion-associated RNA polymerase include viral transcripts that encode IFN system antagonists. The E3L RNA-binding protein impairs activation of the PKR kinase and the OAS synthetases, IFN-induced enzymes that are activated by dsRNA. K3L is a substrate homologue of eIF-2α and is believed to antagonize the translation inhibition mediated by PKR. The B8R and B18R proteins are soluble IFN-γ and IFN-α/β receptor homologues, respectively, that serve as decoys to bind the extracellular induced IFNs. Early viral gene products include proteins and enzymes needed for further uncoating and for viral DNA replication and intermediate transcription. Late genes transcribed after DNA replication encode the structural proteins and enzymes necessary for progeny virion formation in the cytoplasm.