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262 Phylogenetic Characterization of South African HIV-1 Subtype C vif, vpr, vpu, and nef Genes
T. Scriba*1, F. Treurnicht1, J. zur Megede2, S. Barnett2, S. Engelbrecht1, and E. Janse van Rensburg1
1Univ. of Stellenbosch, South Africa and 2Chiron Corp., Emeryville, CA, USA
Background: To date, most phylogenetic studies conducted on South African HIV-1 strains have been focused on the env and gag genes. Although the accessory genes were once considered as nonessential for the pathogenicity of HIV, recent data concerning their high conservation and roles during pathogenesis in vivo and in vitro has shed new light on their importance.
Methods: A cloned 1,370-bp genomic fragment encompassing the vif, vpr, and vpu genes and a 660-bp fragment containing the nef gene of 15 South African HIV-1 subtype C isolates were sequenced. Multiple sequence alignments, predicted amino acid translations, and phylogenetic analyses were performed with the CLUSTALX, GENEDOC, and TREECONW packages respectively.
Results: Amino acid variation in the South African accessory gene isolates correlated well with those previously recorded in subtype C isolates. Vif and vpr showed expected highly conserved protein sequences. Two motifs shown to be critical for Nef’s CD4 down-regulation were variable or absent in most of our isolates and further variation was found in the myristoylation signal of Nef in some isolates. A subtype C-specific LRLL residue signature motif in Vpu was present in all of our isolates. Phylogenetic trees showed statistically significant clustering of our isolates among the subtype C isolates from India, Brazil, Botswana, and Ethiopia. Our sequences did not form a distinguishable South African subcluster and sequence diversity was comparable with the global subtype C diversity.
Conclusions: Our findings provide important information regarding the conserved nature and/or variation of previously reported critical motifs in our subtype C isolates, which may have implications on the functionality of these subtype C accessory genes as well as genetic diversification of HIV-1C. Common residue variations in our isolates correlated well with those seen in the subtype C isolates sequences from India, Botswana, Brazil, and Ethiopia. This is supported by the diversity of our sequences indicating that subtype C infections in the Western Cape, South Africa, do not represent a recent, isolated epidemic from a single point source but rather a highly diverse, rapidly spreading epidemic.
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