Entry of glucose- and glutamine-derived carbons into the citric acid cycle supports early steps of HIV-1 infection in CD4 T cells.
Level 5 - mechanism / opinion, no new human data
Bench research / in vitro mechanistic cellular study without clinical outcomes
PubMed 32373781 · doi:10.1038/s42255-019-0084-1
What was done
Investigated how glucose and glutamine carbon entry into the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) regulates HIV-1 susceptibility in T-cell receptor-stimulated naïve and memory CD4 T-cell subsets. The study evaluated the effects of attenuating glutaminolysis, adding exogenous alpha-ketoglutarate, blocking pyruvate-to-lactate glycolytic flux, and selecting cells with high mitochondrial biomass and OXPHOS activity.
What was found
No quantitative numerical values or exact effect sizes are reported in the abstract. Glutaminolysis was found to be the main pathway fueling the TCA cycle and OXPHOS in stimulated CD4 T cells and was necessary for optimal HIV-1 infection. Exogenous alpha-ketoglutarate rescued infection during attenuated glutaminolysis and promoted reverse transcription. Blocking pyruvate-to-lactate conversion redirected glucose carbon into the TCA and pentose phosphate pathways, increasing OXPHOS and augmenting HIV-1 reverse transcription. HIV-1 infection was significantly higher in cells selected for high mitochondrial biomass and OXPHOS.
Why it matters
This work identifies the balance between oxidative phosphorylation and aerobic glycolysis as a metabolic checkpoint regulating early reverse transcription and susceptibility to HIV-1 in CD4 T cells.
Limits
No numerical estimates, donor numbers, or sample sizes are provided in the abstract. The study relies entirely on in vitro cellular experiments and lacks in vivo or clinical validation.
Cited by
- supports Activated T cells consume glutamine and convert it to alpha-ketoglutarate as an energy source.