PMID- 23874603
OWN - NLM
STAT- MEDLINE
DCOM- 20140218
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 7
DP  - 2013
TI  - HIV-1 Vpr modulates macrophage metabolic pathways: a SILAC-based quantitative 
      analysis.
PG  - e68376
LID - 10.1371/journal.pone.0068376 [doi]
LID - e68376
AB  - Human immunodeficiency virus type 1 encoded viral protein Vpr is essential for 
      infection of macrophages by HIV-1. Furthermore, these macrophages are resistant 
      to cell death and are viral reservoir. However, the impact of Vpr on the 
      macrophage proteome is yet to be comprehended. The goal of the present study was 
      to use a stable-isotope labeling by amino acids in cell culture (SILAC) coupled 
      with mass spectrometry-based proteomics approach to characterize the Vpr response 
      in macrophages. Cultured human monocytic cells, U937, were differentiated into 
      macrophages and transduced with adenovirus construct harboring the Vpr gene. More 
      than 600 proteins were quantified in SILAC coupled with LC-MS/MS approach, among 
      which 136 were significantly altered upon Vpr overexpression in macrophages. 
      Quantified proteins were selected and clustered by biological functions, pathway 
      and network analysis using Ingenuity computational pathway analysis. The 
      proteomic data illustrating increase in abundance of enzymes in the glycolytic 
      pathway (pentose phosphate and pyruvate metabolism) was further validated by 
      western blot analysis. In addition, the proteomic data demonstrate down 
      regulation of some key mitochondrial enzymes such as glutamate dehydrogenase 2 
      (GLUD2), adenylate kinase 2 (AK2) and transketolase (TKT). Based on these 
      observations we postulate that HIV-1 hijacks the macrophage glucose metabolism 
      pathway via the Vpr-hypoxia inducible factor 1 alpha (HIF-1 alpha) axis to induce 
      expression of hexokinase (HK), glucose-6-phosphate dehyrogenase (G6PD) and 
      pyruvate kinase muscle type 2 (PKM2) that facilitates viral replication and 
      biogenesis, and long-term survival of macrophages. Furthermore, dysregulation of 
      mitochondrial glutamate metabolism in macrophages can contribute to 
      neurodegeneration via neuroexcitotoxic mechanisms in the context of NeuroAIDS.
FAU - Barrero, Carlos A
AU  - Barrero CA
AD  - Department of Biochemistry, Temple University School of Medicine, Fels Institute, 
      Philadelphia, Pennsylvania, USA.
FAU - Datta, Prasun K
AU  - Datta PK
FAU - Sen, Satarupa
AU  - Sen S
FAU - Deshmane, Satish
AU  - Deshmane S
FAU - Amini, Shohreh
AU  - Amini S
FAU - Khalili, Kamel
AU  - Khalili K
FAU - Merali, Salim
AU  - Merali S
LA  - eng
GR  - R01 MH086358/MH/NIMH NIH HHS/United States
GR  - R01MH092371/MH/NIMH NIH HHS/United States
GR  - P30 MH092177/MH/NIMH NIH HHS/United States
GR  - R01MH086358/MH/NIMH NIH HHS/United States
GR  - P30MH092177/MH/NIMH NIH HHS/United States
GR  - 5 R01 DA033213-02/DA/NIDA NIH HHS/United States
GR  - P01NS4390/NS/NINDS NIH HHS/United States
GR  - P30MH092177)/MH/NIMH NIH HHS/United States
GR  - R01 MH093271/MH/NIMH NIH HHS/United States
GR  - R01 DA033213/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130712
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Proteome)
RN  - 0 (vpr Gene Products, Human Immunodeficiency Virus)
RN  - 0 (vpr protein, Human immunodeficiency virus 1)
SB  - IM
MH  - Blotting, Western
MH  - Computational Biology
MH  - Glycolysis
MH  - Humans
MH  - Isotope Labeling/*methods
MH  - Macrophages/*metabolism
MH  - *Metabolic Networks and Pathways
MH  - Models, Biological
MH  - Protein Interaction Maps
MH  - Proteome/metabolism
MH  - Proteomics/*methods
MH  - Reproducibility of Results
MH  - Transduction, Genetic
MH  - U937 Cells
MH  - vpr Gene Products, Human Immunodeficiency Virus/*metabolism
PMC - PMC3709966
COIS- Competing Interests: Prasun K. Datta is a PLOS ONE Editorial Board member. This 
      does not alter the authors' adherence to all the PLOS ONE policies on sharing 
      data and materials.
EDAT- 2013/07/23 06:00
MHDA- 2014/02/19 06:00
PMCR- 2013/07/12
CRDT- 2013/07/23 06:00
PHST- 2013/03/10 00:00 [received]
PHST- 2013/05/29 00:00 [accepted]
PHST- 2013/07/23 06:00 [entrez]
PHST- 2013/07/23 06:00 [pubmed]
PHST- 2014/02/19 06:00 [medline]
PHST- 2013/07/12 00:00 [pmc-release]
AID - PONE-D-13-10280 [pii]
AID - 10.1371/journal.pone.0068376 [doi]
PST - epublish
SO  - PLoS One. 2013 Jul 12;8(7):e68376. doi: 10.1371/journal.pone.0068376. Print 2013.