Effects of integration and replication on transcription of the HIV-1 long terminal repeat.

The activity of a promoter is influenced by chromosomal and cell cycle/replication context. We analyzed the influences of integration and replication on transcription of the human immunodeficiency virus (HIV)-1 long terminal repeat (LTR). We found that one requirement for Tat trans-activated expression differed for integrated versus unintegrated HIV-1 LTR. Specifically, the second coding exon of Tat, previously regarded as functionally dispensable, plays a role in the optimal activation of integrated LTRs. We also found that the transcription profile produced from the HIV-1 LTR is influenced by replication. Autonomously replicating vectors that contain the HIV-1 LTR produced patterns of transcription different from counterpart vectors that do not replicate. Both replicating and nonreplicating HIV-1 LTRs remained responsive to Tat.