Effects of the simian virus 40 origin of replication on transcription from the human immunodeficiency virus type 1 promoter

Abstract

Positive and negative effects of DNA replication on gene transcription have been documented in a variety of systems. We examined the effects of the simian virus 40 (SV40) origin of replication on transcription from the human immunodeficiency virus type 1 (HIV-1) promoter, using a transient expression assay in COS-1 cells. The basal activity and Tat transactivation of the HIV promoter were greatly stimulated by the SV40 origin of replication independent of its position relative to the long terminal repeat. These effects were abolished by mutational inactivation of the SV40 origin and were reduced by a DNA replication inhibitor. The magnitude of promoter activation exceeded the increment expected from the increase in template number resulting from DNA replication. The SV40 T-antigen-induced DNA replication augmented the generation of both processive and nonprocessive HIV long terminal repeat-directed transcripts, and Tat primarily enhanced the initiation of those transcripts that were destined to be efficiently elongated. Our data suggest that the HIV promoter displays greater transcriptional activity on replicative DNA templates. This property may influence the activity of integrated HIV provirus and its transition from latency to productive infection.