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

Abstract

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, α trans-minducing factor (αTIF) is a structural component which induces the 5 α genes, the first set of genes transcribed after infection. αTIF requires for induction a cis-acting site present in promoter-regulatory domains of all α genes. The cis site binds 2 host proteins, αH1 and αH2-αH3. These host proteins have a maximum bound molecular weight of 110 000 and 64 000, respectively. DNase 1 protection assays indicate that αH1 protects the entire cis site, whereas αH2-αH3 binds the 3′ domain of the cis site. The methylation interference assays indicate that the contact points of αH1 and αH2-H3 are at the 5′ and 3′ termini of the cis site, respectively. Both proteins can bind to the cis site concurrently. αTIF does not bind directly to DNA but was shown to be present in DNA-protein complexes. The binding of αTIF to these DNA-protein complexes requires the participation of αH1. In contrast to αTIF, the product of the α4 gene, a protein 163 000 in apparent molecular weight binds to DNA directly and regulates genes both positively and negatively. The data indicate that α4 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 α4 protein may reflect both the nature and location of the binding site. The biological implications of the viral trans-acting proteins are discussed.