Differentiation between alpha promoter and regulator regions of herpes simplex virus 1: the functional domains and sequence of a movable alpha regulator.

Abstract

The herpes simplex virus genome consists of at least 3 groups of genes, (.alpha., .beta. and .gamma.), whose expression is coordinately regulated and sequentially ordered in a cascade fashion. The elements involved in regulation of .alpha. genes are a sequence that promotes gene expression and a sequence that confers .alpha. regulation on the gene by responding to trans-acting regulatory signals. The domains of these sequences were mapped by determining the regulation of thymidine kinase (TK) in [mouse] L cells converted to TK+ phenotype by chimeric TK indicator genes. The chimeric genes were constructed from appropriate portions of the TK gene fused to donor sequences derived from the 5'' nontranscribed and nontranslated leader portions of the viral .alpha. gene 4. The natural .beta. TK indicator extending 5'' up to -80 and the chimeric .alpha. TK extending 5'' up to -110 both converted cells to TK+ phenotype but were not regulated. A segment of the regulator region of the .alpha. gene 4, extending 5'' from position -110, confers inducible .alpha.-type regulation when fused to the nonregulated but expressible .beta. TK indicator described above. The extent of gene induction appears to hinge on the size of the regulatory region inserted into the chimeric gene and correlates with the presence of repeated consensus sequences and G+C-rich inverted repeats in the regulatory region of the .alpha. gene 4 and other .alpha. genes.