Characterization of the South African HIV Type 1 Subtype C Complete 5′ Long Terminal Repeat,nef,and Regulatory Genes

Abstract

Human immunodeficiency virus type 1 (HIV-1) subtype C has become the major etiological agent in the global and especially African epidemic. To gain better understanding of the genetic diversity and rapid transmission of HIV-1 subtype C, we have characterized the complete 5' long terminal repeat (LTR) region along with the regulatory genes tat and rev as well as the accessory gene nef of 14 South African HIV-1 subtype C isolates. Phylogenetic analysis revealed a subtype C 5' LTR cluster, as well as subclustering of our nef sequences with various subtype C strains separate from the India and China subclusters. At least 3 NF-kappaB sites were present in the 5' LTR of most isolates and 13 isolates had the subtype C-specific Rev truncation. Some length variation in exon 2 and the absence of a critical cysteine were found in Tat. Residue variation in the myristoylation signal and motifs involved in CD4 and MHC-I downregulation was recorded in our nef gene sequences.

Genetic analysis of Indian HIV-1 nef: subtyping, variability and implications

“…Most of the studies on genomic diversity of HIV have traditionally relied on structural genes, and sequence variation data on regulatory genes is scarce, especially for subtype C viruses. Very few reports have been published on nef sequence analysis from Indian subtype C virus [4,6].…”

Functionally-inactive and immunogenic Tat, Rev and Nef DNA vaccines derived from sub-Saharan subtype C human immunodeficiency virus type 1 consensus sequences

“…Tat, Rev and Nef vaccine candidates were based confirmed the presence of these Cspecific signatures in the LTR, Vpu and Rev regions [41] and [42] as well as the conserved nature of the envelope V3 sequences [40]. It would thus not be unreasonable to speculate about the unexplored subtype factor possibly playing a role in a different structure or function of Tat.…”

“…Although, no unmutated consensus Rev construct was tested in this study to confirm the abrogation of functionality though mutation of the specific residues, such a consensus Rev protein could be expected to be functionally active as its amino acid sequence reveals no abnormal residue combinations or substitutions in the functional domains [41].…”

“…We previously isolated and characterized 15 HIV-1 subtype C isolates from South Africa designated TV001 through TV010, TV012-TV014, TV018 and TV019 [40], [41], [42], [43] and [44]. The Tat, Rev and Nef amino acid sequences of 14 of these 15 subtype C isolates were used to derive respective consensus sequences (designated TV Cons) by taking the most prevalent residue for each amino acid position across the reading frames of the three regulatory proteins.…”

Phylogenetic Characterization of Six Full-Length HIV-1 Subtype C Molecular Clones from Three Patients: Identification of Rare Subtype C Strains Containing Two NF-κB Motifs in the Long Terminal Repeat

“…This feature was previously observed in the South African subtype C strains as well. 18 An additional seven amino acid deletion was observed in Rev exon II in both the clones isolated from subject NIRT723, which is also seen in the infectious subtype C molecular clone pIndie-C1. However, the functional consequences of this deletion are not known (Fig.…”