Host cell proteins bind to the cis-acting site required for virion-mediated induction of herpes simplex virus 1 α genes

Abstract

The herpes simplex virus 1 genes form at least five groups (α, β1, β2, γ1, and γ2) whose expression is coordinately regulated and sequentially ordered in a cascade fashion. In productively infected cells, the α genes are expressed first, and a virion protein, the α-trans-inducing factor (α-TIF), acts in trans to enhance their expression. Induction of the α genes by α-TIF requires the presence of a trans-induction cis-acting site (α-TIC), and one to three homologs of the α-TIC sequence are contained in the regulatory domains of all α genes. We report that small DNA fragments from regulatory domains of α0, α4, and α27 genes containing α-TIC homologs formed complexes with host but not viral proteins. DNase protection studies indicated that the major host protein complex α-H1 detected in DNA gel retardation assays bound asymmetrically across the α-TIC site. All DNA fragments containing α-TIC homologs, but not those lacking the homolog, competed for the binding of this complex. The location of the binding site of the other host proteins is not yet known. Simian virus 40 DNA fragments containing a homolog of the α-TIC sequence also competed with herpes simplex virus DNA fragments carrying authentic α-TIC homologs for the α-H1 protein complex.