Intra-Clade C signature polymorphisms in HIV-1 LTR region: The Indian and African lookout

Abstract

Polymorphisms occurring in LTR (Long Terminal Repeat) region can profoundly impact pathogenicity, transmission and biology of Human Immunodeficiency Virus Type 1 (HIV-1). We investigated intra-clade polymorphisms, associated with HIV-1 clade-C infections that occur in India and Africa. Plasma samples were obtained from 24 HIV-infected ART-experienced individuals. Next Generation Sequencing was performed on Illumina Hi Seq X system. Sequence analysis was done using MEGA v7. Transcription factor binding sites (TFBS) were investigated to unveil signature sequences. Signature nucleotides in Indian sequences were observed at 19 positions, of which 7 nucleotide signatures occurred in transcription binding sites (TFBS), namely NF-AT-II, NF-AT-III, USF, TCF- 1alpha, Sp1-I and TAR. Intra-clade C variations in HIV-1 LTR that inscribe signature nucleotides in Indian sequences lead to formation monophyletic cluster of Indian sequences. Moreover, occurrence of intra-clade signature nucleotides was observed at the key positions in the transcription factor binding sites in Indian and African clade-C sequences.

Keywords: Next Generation Sequencing (NGS); Nuclear Factor Activated T-cells (NF-AT); Specificity protein 1 (Sp1); T-cell specific factor-1 alpha (TCF-1 alpha); Trans-activation response (TAR) element; Upstream Stimulatory Factor (USF).