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Published on: December 26, 2013
Metabolite profiles of human immunodeficiency virus infected CD4+ T cells and macrophages using LC-MS/MS analysis
Joseph A Hollenbaugh1, Joshua Munger, Baek Kim
1Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
Insights
Human immunodeficiency virus type 1 (HIV-1) alters cell metabolism differently in CD4+ T cells and macrophages. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) effectively monitored these distinct metabolic changes during HIV infection.
Area of Science:
- Virology
- Cell Biology
- Metabolomics
Background:
- Human immunodeficiency virus type 1 (HIV-1) infects key immune cells, including CD4+ T cells and macrophages.
- Understanding HIV-1's impact on host cell metabolism is crucial for developing therapeutic strategies.
- Previous studies have indicated metabolic reprogramming in HIV-1 infected cells, but cell-type specific differences require further investigation.
Purpose of the Study:
- To investigate and compare the metabolic alterations induced by HIV-1 in primary human CD4+ T cells and a macrophage model system.
- To evaluate the utility of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for monitoring HIV-1-driven metabolic changes.
Main Methods:
- Primary human CD4+ T cells were infected with HIV-1.
- A macrophage model system using differentiated U1 (HIV-1 producing) and differentiated U937 (control) cells was established.
- Glucose uptake was measured in both cell types.
- LC-MS/MS-based metabolomic analysis was performed to profile metabolite changes.
Main Results:
- HIV-1 infected CD4+ T cells exhibited increased glucose uptake and elevated levels of several metabolites.
- HIV-1 producing macrophages showed significantly reduced glucose uptake and decreased levels of glycolytic intermediates.
- The study identified distinct metabolic profiles between infected CD4+ T cells and HIV-1 producing macrophages.
Conclusions:
- HIV-1 infection leads to divergent metabolic outcomes in its primary target cell types, CD4+ T cells and macrophages.
- LC-MS/MS is a powerful and effective technology for comprehensively monitoring metabolic alterations during HIV-1 infection.
- These findings highlight the importance of considering cell-type specific metabolic responses in HIV-1 pathogenesis and treatment strategies.
Abstract:
Human immunodeficiency virus type 1 (HIV-1) infects both activated CD4+ T cells and macrophages. We tested if liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology can monitor metabolic alterations induced by HIV-1 in the infected cells. Here we monitored glucose uptake and conducted LC-MS/MS-based metabolomic analysis in HIV-1 infected primary human CD4+ T cells and a macrophage model system: differentiated U1 (HIV-1 producing) and differentiated U937 (control) cells. HIV-1 infected CD4+ T cells have higher glucose uptake and increases in several metabolite pool sizes, whereas HIV-1 producing macrophages had substantial reductions in glucose uptake and steady state glycolytic intermediates. This data suggests that the two HIV-1 target cell types exhibit very different metabolic outcomes during viral production. This study also validates the LC-MS/MS technology as an effective metabolomic approach to monitor various metabolic alterations made by HIV-1 infection.

