Genetic Variability and Function of the Long Terminal Repeat from Syncytium-Inducing and Non-Syncytium-Inducing Human Immunodeficiency Virus Type 1

Abstract

We analyzed sequence variability and function of the long terminal repeat (LTR) from syncytium-inducing (SI) and non-syncytium-inducing (NSI) HIV-1. Twenty LTR DNA clones were obtained by polymerase chain reaction amplification and molecular cloning from short-term cultures of SI and NSI viruses from an AIDS patient and two asymptomatic individuals, respectively. All the LTR clones tested contained multiple nucleotide changes (mostly G-to-A transitions), compared to the subtype B concensus sequence, which were clustered within the negative regulatory element, including NF-AT, USF, and TCF-lα binding sites. The core promoter/TAR region sequences were highly conserved. The basal and Tat-mediated transcriptional activities of selected LTR clones tested were 0.1 to 1 and 0.2 to 0.5 times that of the control, respectively, regardless of the SI or NSI origin of the clones. Phylogenetic analysis revealed interisolate sequence divergence in the LTR that was similar but not identical to previously analyzed vif sequences from the same samples. In particular, the interisolate distances from reference sequences differed for the LTR and vif. This raises the possibility that recombination occurred between corresponding LTR and vif loci of the quasispecies present in the isolates described here.