[27] LONG TERMINAL REPEAT SEQUENCE ANALYSIS OF THE HIV-1C EPIDEMIC IN ETHIOPIA DEMONSTRATING ASYMMETRIC PREVALENCE OF THE TWO CO-CIRCULATING GENOTYPES C AND C’: INDICATION FOR BIOLOGICAL ADVANTAGE OF THE C GENOTYPE

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] LONG TERMINAL REPEAT SEQUENCE ANALYSIS OF THE HIV-1C EPIDEMIC IN ETHIOPIA DEMONSTRATING ASYMMETRIC PREVALENCE OF THE TWO CO-CIRCULATING GENOTYPES C AND C’: INDICATION FOR BIOLOGICAL ADVANTAGE OF THE C GENOTYPE

[AUTHOR(S):] G Pollakis, T van Opijnen, A Kliphuis, A Abebe, J Goudsmit and MP de Baar
Department of Human Retrovirology, Academic Medical centre, University of Amsterdam, Amsterdam, the Netherlands

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 27
Antiviral Therapy 2003; 8(Suppl. 1):S191

[ABSTRACT:] Background: The Ethiopian HIV-1 epidemic is caused by subtype C but the analysis of the envelope gene revealed two distinguishable cocirculating C genotypes. We analysed the long terminal repeat (LTR) region in order to correlate the genotype to the pathogenic trends of the virus.

Methods: The LTR region and part of the 5´ untranslated region (700 nt) from 22 HIV-1 positive Ethiopian individuals were sequenced. Phylogenetic analysis was performed with the distance matrix been calculated and the trees topology of the isolates determined according to the Kimura 2-parameter/neighbor-joining model. The U3-LTR regions were cloned into molecular HIV-1 clones.

Results: The LTR sequence analyses revealed the presence of two distinct genotypes C (n=13) and C´ (n=4), supported by high bootstrap values confirming the finding for the C2V3 envelope region. We also found that the two co-circulating genotypes gave rise to unidirectional recombinant viruses. The LTR analysis of the 22 isolates and the comparison to their corresponding C2V3-envelope sequence revealed nine intra-subtype C/C´ recombinant isolates. Thus, the prevalence of C/C´ recombinant viruses is at least 40%. The C2V3 sequences of all recombinants belonged to the genotype C´, whereas every LTR belonged to the genotype C. Furthermore, sequences from India were phylogenetically closer to the sequences from the C´ Ethiopian group than to the C group. Nucleotide differences between the two groups were identified in the NF-AT, TCF-1α and SP-1 transcription factor binding sites, whereas the NF-κB and NRE-core sequences were identical. Molecular clones were engineered using a U3-LTR region including the transcription factor binding sites from both groups C and C′ and were investigated in order to discern biological differences.

Conclusions: The surveillance of the HIV-1 circulating strains, especially in areas of high prevalence such as Ethiopia is crucial for future vaccine studies. We have identified that in Ethiopia two strains of subtype C (C and C′) are co-circulating and demonstrated that recombinant progeny exist, possibly through unidirectional recombination and evolutionary pressure on the respective biological functions of the LTR promoter and the envelope protein. There is indication that one group may have a biological advantage over the other.

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