Proteomic studies reveal coordinated changes in T-cell expression patterns upon infection with human immunodeficiency
Jeffrey H Ringrose1, Rienk E Jeeninga, Ben Berkhout
1K1-262, Academic Medical Center, University of Amsterdam, Clinical Proteomics Group, Medical Biochemistry, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. d.speijer@amc.uva.nl
Insights
Human immunodeficiency virus type 1 (HIV-1) infection alters T cell protein levels, causing metabolic shifts and influencing apoptosis and transport proteins. This proteomic study reveals key cellular changes during HIV infection.
Area of Science:
- Proteomics
- Immunology
- Virology
Background:
- Human immunodeficiency virus type 1 (HIV-1) infection significantly impacts host cell biology.
- Understanding cellular changes in T cells is crucial for HIV-1 pathogenesis research.
Purpose of the Study:
- To comprehensively analyze proteomic alterations in human T cells following HIV-1 infection.
- To identify specific proteins and pathways affected by HIV-1 at the cellular level.
Main Methods:
- Two-dimensional differential in-gel electrophoresis proteomic analysis.
- Identification and quantification of differentially expressed proteins in infected T cells.
Main Results:
- 15% of 2,000 detected protein spots showed differential expression at peak HIV-1 infection.
- 93 proteins were identified with altered abundance; 27 downregulated and 66 upregulated.
- Significant metabolic rerouting observed: downregulated glycolysis and enhanced mitochondrial oxidation.
- Proteins involved in apoptotic signaling and intracellular transport were notably affected.
Conclusions:
- HIV-1 infection induces widespread proteomic changes in T cells.
- Metabolic reprogramming, apoptosis modulation, and altered intracellular transport are key cellular responses to HIV-1.
- These findings provide insights into HIV-1's impact on cellular functions and potential therapeutic targets.
Abstract:
We performed an extensive two-dimensional differential in-gel electrophoresis proteomic analysis of the cellular changes in human T cells upon human immunodeficiency virus type 1 (HIV-1) infection. We detected 2,000 protein spots, 15% of which were differentially expressed at peak infection. A total of 93 proteins that changed in relative abundance were identified. Of these, 27 were found to be significantly downregulated and 66 were upregulated at peak HIV infection. Early in infection, only a small group of proteins was changed. A clear and consistent program of metabolic rerouting could be seen, in which glycolysis was downregulated and mitochondrial oxidation enhanced. Proteins that participate in apoptotic signaling were also significantly influenced. Apart from these changes, the virus also strongly influenced levels of proteins involved in intracellular transport. These and other results are discussed in light of previous microarray and proteomic studies regarding the impact of HIV-1 infection on cellular mRNA and protein content.
