Characterisation of the long terminal repeat regions of south african human immunodeficiency virus type 1 isolates

The 5' long terminal repeat (LTR) region of the integrated proviral human i mmunodeficiency virus type 1 (HIV-1) template encodes cis-acting sequences for cellular proteins that are responsible for initiating viral transcripti on. The objective of this study was to analyse the LTR regions of isolates from a broad spectrum of South African HIV-1 infected individuals to (i) de termine if sequence diversity was sufficient to allow for subtyping on the basis of this region, and (ii) to note any specific or unusual alterations in promoter binding motifs that may be common to this group of isolates or specific HIV-1 subtypes within this group. A total of 60 isolates were subt yped by heteroduplex mobility assay (HMA) and by phylogenetic analysis, usi ng both the env and gag regions. Phylogenetic relatedness within the LTR re gion demonstrated the suitability of this region for use in HIV-1 subtype d esignation. The presence of additional NF-kappaB binding elements as well a s altered USF binding sites were features common to subtype C HIV-1 isolate s. Although the biological relevance of these alterations within the HIV-1 LTR with respect to viral replicative capacity and patient disease progress ion is unknown, there is strong support to suggest that in the presence of these features, there is increased gene transcription in subtype C isolates , and that this would be further increased in the presence of secondary inf ection.