HSV-1 Activation of HIV-1 Transcription Is Augmented by a Cellular Protein That Binds near the Initiator Element

A cellular DNA binding protein, which we term Leader Binding Protein-2 (LBP-2), binds near the transcriptional initiation site of the human immunodeficiency virus type 1 (HIV-1) promoter. This protein recognizes a motif similar to that of LBP-1, a putative repressor of transcription (Kato, H., et al., Science , 251, 1476-1479, 1991). LBP-2 is associated with transcriptional activation of HIV-1 by herpes simplex virus type 1 (HSV-1). Electrophoretic mobility shift assays showed that nuclear levels of this protein increase markedly following HSV-1 infection. Mutations of the LBP binding motif eliminate LBP-2 binding and interfere with HIV-1 activation by HSV-1. When inserted into an unrelated promoter, this motif confers transcriptional responsiveness to HSV-1 infection. Proteins that bind near the initiator element may be important regulators of HIV-1 gene expression.