HIV type 1 C and C' subclusters based on long terminal repeat sequences in the Ethiopian type 1 subtype C epidemic

While the Ethiopian HIV-1 epidemic is dominated by subtype C, two distinguishable cocirculating C genotypes have been identified based on sequences of the C2V3 envelope region. In this study we sequenced and analyzed the long terminal repeat (LTR) sequence from 22 Ethiopian HIV-1-positive individuals. The two phylogenetically distinguishable genotypes C (n = 13) and C' (n = 4) are separated by significant bootstrap values. Nucleotide differences between the two groups were identified in the NF-AT, TCF-1alpha, and SP1 transcription factor binding sites, whereas the NF-kappaB and NRE-core sequences were identical between the two groups. Five isolates that could not be classified C or C' were found to be recombinants within the LTR sequence upon boots can analysis. Comparison of all the LTR sequences with their corresponding C2V3 envelope sequence revealed four intersubtype C/C' recombinant isolates. Thus, the prevalence of C/C' recombinant viruses is well over 40%. Interestingly, the C2V3 envelope sequences of all recombinant viruses belonged to the genotype C', whereas every LTR sequence belonged to the genotype C. This result indicates that recombination between the two genotypes is unidirectional, possibly as the result of evolutionary pressure on the respective biological functions of the LTR promoter and the envelope protein.