Genetic architecture of HIV-1 genes circulating in north India & their functional implications

Abstract

This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Myanmar with 3 copies of Nfκb sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted.

Fig. 1

Mosaic pattern and organization of transcription factor binding sites in HIV-1 LTR reported from north India: (A) B/C LTR showing 3 NF-κB (B) B LTR showing 2 NF-κB. Source: Ref. 22.

Fig. 2

Bootscan, informative and phylogenetic analysis of NIIPGI- IND-TatA9 variant using SimPlot ver 3.5.1. Bootscan analysis was carried out using Kimura (2-parameter) with a window size of 40 bp and a stepsize of 20 bp. Precise breakpoint and genomic makeup of the recombinant A9 isolate is shown.

Fig. 3

Genetic analysis of the two Vpr recombinant samples from north India: Similar to Fig. 2, genetic tools were used to characterize the two Vpr sequences. The nature of the mosaic genome segments are shown along with their phylogenetic analysis. Source: Ref. 33.

Fig. 4

Radial phylogenetic analysis of the envelope sequences. Note the Indian CRF02_AG clustering with earlier described CRF_02AG strains. The other two clusters are B and C subtype-specific.