The trans-activation of herpes simplex virus gene expression: comparison of two factors and their cis sites

In herpes simplex virus-infected cells, gene expression is tightly regulated. In this review, we compare the properties of two trans-activating factors which regulate the expression of viral genes. The first, alpha trans-inducing factor (alpha TIF) is a structural component which induces the 5 alpha genes, the first set of genes transcribed after infection. Alpha TIF requires for induction a cis-acting site present in promoter-regulatory domains of all alpha genes. The cis site binds 2 host proteins, alpha H1 and alpha H2-alpha H3. These host proteins have a maximum bound molecular weight of 110,000 and 64,000, respectively. DNase 1 protection assays indicate that alpha H1 protects the entire cis site, whereas alpha H2-alpha H3 binds the 3' domain of the cis site. The methylation interference assays indicate that the contact points of alpha H1 and alpha H2-H3 are at the 5' and 3' termini of the cis site, respectively. Both proteins can bind to the cis site concurrently. Alpha TIF does not bind directly to DNA but was shown to be present in DNA-protein complexes. The binding of alpha TIF to these DNA-protein complexes requires the participation of alpha H1. In contrast to alpha TIF, the product of the alpha 4 gene, a protein 163,000 in apparent molecular weight binds to DNA directly and regulates genes both positively and negatively. The data indicate that alpha 4 protein can bind to at least 2 binding sites differing in nucleotide sequence and which can be present in promoters, across the transcription initiation sites, and in 5' transcribed non-coding sequences. The regulatory functions of the alpha 4 protein may reflect both the nature and location of the binding site. The biological implications of the viral trans-acting proteins are discussed.