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Functional characterization of HIV-1 Tat exon-1 variants from North India and their implications on HIV-1 transactivation and TAR interaction
© Ronsard et al; licensee BioMed Central Ltd. 2014
Published: 27 May 2014
HIV-1 virus is a rapidly evolving virus due to genetic variability through its rapid replication, mutation and recombination potential which is a major hurdle in vaccine development. One of the effective ways to modulate HIV-1 infection is to target viral proteins; among the viral proteins, Tat plays a major role in HIV-1 pathogenesis. It activates viral gene expression through TAR interaction. The aim of this study was to characterize genetic and functional variants of Tat exon-1 from HIV-1 patients from North India.
DNA was isolated from PBMCs and Tat exon-1 was PCR amplified with specific primers followed by cloning, sequencing and sequence analysis using bioinformatics tools for predicting subtypes, recombination events, conservation of domains and phosphorylation sites. Unique Tat exon-1 variants were functionally characterized for LTR transactivation, TAR interaction and cell death.
Genetic analysis of Tat exon-1 variants revealed 90% subtype C and 10% B/C recombinants, and the functional characterization showed varying levels of LTR transactivation, TAR interaction and cell death. A single mutation (S46F) in Tat exon-1 variants showed enhanced LTR transactivation through strong interaction with TAR.
Possible role of Tat exon-1 variants in shaping the current HIV-1 epidemic in North India is discernible. Natural substitutions across the conserved functional domains were observed. There is evidence for the emergence of B/C recombinants within Tat exon-1. The impact of genetic variations in Tat exon-1 on its pivotal functions is apparent. These are likely to have implications for HIV-1 pathogenesis and strategies of vaccine formulations.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.