Separation of sequences defining basal expression from those conferring alpha gene recognition within the regulatory domains of herpes simplex virus 1 alpha genes.

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Abstract
The genes of herpes simplex virus 1 form 3 major groups (.alpha., .beta. and .gamma.) whose expression is coordinately regulated and sequentially ordered in a cascade fashion. To determine how the infected cell differentiates between these gene groups, .alpha.-regulated chimeric genes were constructed in earlier studies by fusing the structural sequences of the thymidine kinase (TK) gene, a .beta. gene, to the 5'' noncoding sequences of .alpha. genes. These studies showed that 1 or more structural components of the virion act in trans to increase .alpha. gene expression, and the 5'' noncoding sequences of .alpha. genes contain cis-acting domains that promote gene expression and confer .alpha.-gene regulation. These 2 domains could be moved independently, but the regulatory domain required a promoter for its function. The properties of 3 sequences containing features common to the regulatory regions of all .alpha. genes is reported. Sequence 1, containing (G+C)-rich inverted repeats, increased the basal level of TK expression when fused 5'' to either the .alpha. gene 4 promoter or the truncated .beta. TK promoter. The effect was to some extent orientation dependent. Sequence 1 restored .beta. regulation to the truncated .beta. TK promoter but did not confer .alpha.-specific regulation on any of the chimeric genes tested. Sequences 2 (49 base pairs) and 3 (29 base pairs), containing an (A+T)-rich homolog from .alpha. gene 27 and .alpha. gene 0, respectively, restored .alpha.-specific regulation to the .alpha. promoter gene but only sequence 2 conferred .alpha. regulation on the truncated .beta. promoter gene. Evidently, in natural .beta. TK the promoter and regulatory domains overlap, sequence 1 determines basal level of expression and substitutes for a promoter component that is essential for .beta. but not .alpha. regulation, and conversion of a gene with a promoter into an .alpha. gene requires 2 elements. Sequence 2 may contain both whereas sequence 3 contains only 1.