Journal of Bioequivalence & Bioavailability

Analysis of the HIV-1 Tat exon 2 gene motifs as a potent candidate for therapeutics against HIV infection

3^rd World Congress Bioavailability & Bioequivalence

March 26-28, 2012 Marriott Hotel & Convention Centre, Hyderabad, India

Sneham Tiwari and Shailendra K. Saxena

Posters: J Bioequiv Availab

Abstract:

H IV-1 tat gene is a regulatory gene responsible for initiation and elongation of viral transcription through the LTR transactivation, composed of two coding exons yielding a protein of 101 amino acids. Exon 1 (1?72aa) is important for viral transcription and Exon 2 (73?101 aa) is believed to have major role in cell adhesion and cellular uptake of the exogenous Tat and facilitates apoptosis. The aim of our study was to analyse HIV-1 tat exon 2 and to assess its potential for therapeutics against HIV infection. Comparative analysis of nucleotide sequences of HIV-1 patients with Indian reference isolate (HIV-1C- IN) showed that samples had ~75% similarity with HIV-1C-IN and phylogenetic analysis showed them falling in close cluster of HIV-1 clade C. The tat exon 2 sequences displayed the presence of conserved RGD motif and ESKKKVE motif. Presence of RNA binding domains was reported, which if undergoes any mutation may alter the binding of the Tat with TAR element, essential for the Tat-mediated trans-activation. Hence making the domain a potential drug target. Further sequence analysis of the samples suggest that in CCMB121 lysine residue was not seen to be conserved at position number 90 which may be hypothesized in downregulating the HIV-1 replication. Even though Tat plays an important role in viral transcription, till date there is no Tat based drugs designed, for this the novel CTL epitope (DPSGSEESK) observed by us can be analysed for posing as drug target