Replication and Transcriptional Control

MCV is typical of poxviruses in its genome structure and cytoplasmic site of replication and is expected to be functionally similar to the group as a whole in these respects. The open reading frames detected by MCV DNA sequence analysis show tight clustering of genes, transcribed from opposing strands in either direction, as seen in vaccinia virus. Transcriptional promoter and termination sequences are highly conserved by comparison with orthopoxviruses and, being AT-rich, are particularly obvious in relation to the GC-rich coding sequences of MCV DNA. For example, the 15 bp core promoter in the 5' non-translated region of 29 known vaccinia early genes is similar in sequence and location in the corresponding MCV genes. Analogously, the TAAAT transcriptional initiator sequence of vaccinia late gene promoters is conserved in MCV homologues. Some orthopoxvirus genes contain both early and late promoter consensus sequences, and this remarkable combination of transcription signals is preserved in most of their MCV counterparts. Intermediate vaccinia promoters containing an AAANAA core sequence located 11—13 nucleotides upstream of a

TAAA transcription initiator site are also conserved in the MCV gene homologues.

Transcription stops 20-50 bp downstream of the TTTTTNT termination sequence of vaccinia early genes and this sequence is present at the end of many predicted MCV early genes. Termination of transcription of late genes is poorly characterized but consensus early promotor sequences are often present, implying adjacent early genes.

Poxvirus DNA is replicated as a concatemer and resolution to genomic DNA in vaccinia is controlled by near terminal, late promoter-like sequences consisting of a TAAAT element separated by 7-9 nucleotides from a run of 5-7 consecutive T residues; this signal is conserved in MCV DNA.

These features suggest that genetic organization, control of gene expression and DNA replication in MCV is similar in many respects to vaccinia. A recombinant vaccinia virus containing an MCV type I DNA fragment, which includes the p43K gene encoding the major envelope antigen, has been used to demonstrate that MCV promoter elements are recognized by the transcriptional mechanisms of a serologically unrelated poxvirus.

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