Frame-shift mutations within the vaccinia virus A-type inclusion protein gene.

The genetic basis for the failure of vaccinia virus (strain WR) to form a full-length 150 kiloDalton (kDa) A-type inclusion protein was determined by sequencing a 4.1-kb pair segment of DNA and analyzing its transcription products. Open reading frames predicted to encode slightly overlapping 84.5- and 27.1-kDa proteins homologous to contiguous N-terminal segments of the A-type inclusion protein of cowpox virus were found. A putative deletion of two adjacent nucleotides occurring within several consecutive AG repeats and an insertion of 8 nucleotides accounted for the first and second reading frame shifts, respectively. Additional small mutations affecting reading frames were present in the C-terminal region of the gene. The vaccinia and cowpox virus mRNAs encoding the disparate size A-type inclusion proteins were similar in length, had equivalent 5' and 3' ends, and were expressed late in infection indicating the absence of mutations affecting transcriptional signals.