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Journal of Virology, July 2004, p. 6883-6890, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.6883-6890.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Human Immunodeficiency Virus Type 1 Promoter Contains a CATA Box Instead of a TATA Box for Optimal Transcription and Replication

Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam ,¹ Section of Population Biology, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, 1098 SM Amsterdam, The Netherlands²

Received 12 December 2003/ Accepted 18 February 2004

The human immunodeficiency virus type 1 (HIV-1) transcriptional promoter contains a single polymorphism in the TATA box. Most subtypes contain the sequence TATAAGC, but subtype E and some recombinant AG strains have the sequence TAAAAGC. Based on mutagenesis studies of cellular RNA polymerase II (pol II) promoters, it has been proposed that the subtype E TATA box is nonfunctional due to the T-to-A substitution at the critical position 3. By means of transcription and virus replication assays, we demonstrate that the true TATA box motif within the viral long terminal repeat (LTR) promoter starts two nucleotides further upstream. Because of this realignment, subtype E has the sequence CATAAAA and all other subtypes have the sequence CATATAA. The polymorphism therefore has shifted from position 3 to position 5 and is no longer incompatible with efficient transcription according to rules determined for cellular pol II promoters. In addition, through sensitive competition experiments, we demonstrate that the CATA box of subtypes B and E can be improved for replication by the mutations 1T and 5T, respectively. The fact that the fitness of both subtype LTRs can be increased by specific point mutations in the CATA box suggests that the transcriptional promoter of HIV-1 is fine-tuned towards a suboptimal level of replication. However, this replication rate may be optimal in the in vivo context of an infected individual.

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