PMID- 24367500
OWN - NLM
STAT- MEDLINE
DCOM- 20141008
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - Effect on HIV-1 gene expression, Tat-Vpr interaction and cell apoptosis by 
      natural variants of HIV-1 Tat exon 1 and Vpr from Northern India.
PG  - e82128
LID - 10.1371/journal.pone.0082128 [doi]
LID - e82128
AB  - BACKGROUND: 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. METHODS: HIV-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. RESULTS: Exon 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. CONCLUSIONS: Extensive 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.
FAU - Lata, Sneh
AU  - Lata S
AD  - Department of Microbiology, University College of Medical Sciences and Guru Teg 
      Bahadur Hospital, Delhi, India.
FAU - Ronsard, Larance
AU  - Ronsard L
AD  - Department of Microbiology, University College of Medical Sciences and Guru Teg 
      Bahadur Hospital, Delhi, India ; Laboratory of Virology, National Institute of 
      Immunology, New Delhi, India.
FAU - Sood, Vikas
AU  - Sood V
AD  - Department of Microbiology, University College of Medical Sciences and Guru Teg 
      Bahadur Hospital, Delhi, India ; Laboratory of Virology, National Institute of 
      Immunology, New Delhi, India.
FAU - Dar, Sajad A
AU  - Dar SA
AD  - Department of Microbiology, University College of Medical Sciences and Guru Teg 
      Bahadur Hospital, Delhi, India.
FAU - Ramachandran, Vishnampettai G
AU  - Ramachandran VG
AD  - Department of Microbiology, University College of Medical Sciences and Guru Teg 
      Bahadur Hospital, Delhi, India.
FAU - Das, Shukla
AU  - Das S
AD  - Department of Microbiology, University College of Medical Sciences and Guru Teg 
      Bahadur Hospital, Delhi, India.
FAU - Banerjea, Akhil C
AU  - Banerjea AC
AD  - Laboratory of Virology, National Institute of Immunology, New Delhi, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131219
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Gene Products, vpr)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Apoptosis/*genetics
MH  - Blotting, Western
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Exons/genetics
MH  - Female
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Viral/*genetics
MH  - Gene Products, vpr/*genetics
MH  - HIV-1/*genetics
MH  - HeLa Cells
MH  - Humans
MH  - India
MH  - Male
MH  - Middle Aged
MH  - Young Adult
MH  - tat Gene Products, Human Immunodeficiency Virus/*genetics
PMC - PMC3868622
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/12/25 06:00
MHDA- 2014/10/09 06:00
PMCR- 2013/12/19
CRDT- 2013/12/25 06:00
PHST- 2013/05/29 00:00 [received]
PHST- 2013/10/18 00:00 [accepted]
PHST- 2013/12/25 06:00 [entrez]
PHST- 2013/12/25 06:00 [pubmed]
PHST- 2014/10/09 06:00 [medline]
PHST- 2013/12/19 00:00 [pmc-release]
AID - PONE-D-13-22589 [pii]
AID - 10.1371/journal.pone.0082128 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 19;8(12):e82128. doi: 10.1371/journal.pone.0082128. 
      eCollection 2013.