After penetration viral DNA is released by a two stage uncoating process. The first stage is initiated immediately after engulfment by preexistent host enzymes, which break down the viral membrane part of the coat protein and the membrane of the endocytic vesicle to free the nucleoprotein into the cytoplasm. The resulting transcripts are processed within the core and functional immediate early RNA emerge. They code for proteins involved in the final uncoating event and for the enzymes necessary for the second set of mRNAs, delayed early. Finally after viral DNA replication begins, late mRNAs appear,while some early messages continue to be made.
Transcription continues until about seven hours after infection.
None of the early genes have introns. Sequences upstream of the coding region are extremely rich in adenylate and thymidilate residues, but do not resemble eukaryotic promoters. Elimination of a single T prevents termination. Vaccinia shuts off host protein synthesis within a few hours of infection, about the same time as late viral proteins appear. Regulation of late transcription not completely understood.