Interferon sensitivity of expression of histone H5/H1(0)-vaccinia thymidine kinase fusion genes expressed by recombinant vaccinia viruses is enhanced by shortening the histone sequence.

To elucidate the structural basis responsible for the reduced IFN sensitivity of expression of the histone H1(0) and H5 gene, integrated into the vaccinia virus genome, vaccinia virus thymidine kinase (VV-TK)-histone H1(0)/H5 fusion genes were constructed and translocated into the TK locus of the VV genome. The chimeric genes, consisting of parts of either of the two histone genes and the 5' or 3' half of the TK gene, respectively, were expressed as histone-TK fusion proteins under the control of either the VV-TK promoter or the early sequences of the VV 7.5K promoter. IFN sensitivity of the expression of histone-TK fusion genes was shown to be influenced by the relative length of the histone sequence. Expression of fusion genes containing more than 45% cellular sequence either from the 5' or the 3' part of one of the two histone genes showed clearly reduced IFN sensitivity compared to the expression of VV-TK. On the other hand, by further reducing the relative amount of histone H5 or H1(0) sequence to 32%, the IFN sensitivity of expression of the corresponding fusion gene was drastically enhanced to levels indistinguishable from those of VV-TK.