Abstract
BackgroundSince HIV-1 Tat and Vpr genes are involved in promoter transactivation, apoptosis, etc, we carried out studies to find out nature and extent of natural variation in the two genes from seropositive patients from Northern India and determined their functional implications.MethodsHIV-1 tat exon 1 and vpr were amplified from the genomic DNA isolated from the blood of HIV-1 infected individuals using specific primers by Polymerase Chain reaction (PCR) and subjected to extensive genetic analysis (CLUSTAL W, Simplot etc). Their expression was monitored by generating myc fusion clones. Tat exon 1 and Vpr variants were co-transfected with the reporter gene construct (LTR-luc) and their transactivation potential was monitored by measuring luciferase activity. Apoptosis and cell cycle analysis was done by Propidium Iodide (PI) staining followed by FACS.ResultsExon 1 of tat was amplified from 21 samples and vpr was amplified from 16 samples. One of the Tat exon 1 variants showed phylogenetic relatedness to subtype B & C and turned out to be a unique recombinant. Two of the Vpr variants were B/C/D recombinants. These natural variations were found to have no impact on the stability of Tat and Vpr. These variants differed in their ability to transactivate B LTR and C LTR promoters. B/C recombinant Tat showed better co-operative interaction with Vpr. B/C/D recombination in Vpr was found to have no effect on its co-operativity with Tat. Recombinant Tat (B/C) induced more apoptosis than wild type B and C Tat. The B/C/D recombination in Vpr did not affect its G2 arrest induction potential but reduced its apoptosis induction ability.ConclusionsExtensive sequence and region-specific variations were observed in Tat and Vpr genes from HIV-1 infected individuals from Northern India. These variations have functional implications & therefore important for the pathogenicity of virus.
Highlights
Human Immunodeficiency Virus (HIV) was discovered in 1983
At least 10 percent of circulating HIV-1 strains comprise of intersubtype recombinants [7,8,9]
The aim of the present study was to find out the nature of genetic variations in Tat exon 1 and Vpr found in HIV-1 infected individuals from North India and to determine their functional significance
Summary
Human Immunodeficiency Virus (HIV) was discovered in 1983. It has become one of the biggest health problems throughout the world despite widespread use of ARV (Anti-retroviral) agents. HIV-1 isolates from all over the world have been divided into four groups, namely M, N, O and P. More than 90 percent of HIV/AIDS cases are due to this group. At least 10 percent of circulating HIV-1 strains comprise of intersubtype recombinants [7,8,9]. Recent studies indicate that subtype C (responsible for majority of the infections world wide (more than 56%) accounts for more than 98 percent of the infections in the Indian subcontinent [10]. Since HIV-1 Tat and Vpr genes are involved in promoter transactivation, apoptosis, etc, we carried out studies to find out nature and extent of natural variation in the two genes from seropositive patients from Northern India and determined their functional implications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
