Apagado de la síntesis de lípidos impulsado por IFN en células T CD4⁺ durante la infección aguda por SIV y la...

Cellular metabolism regulates HIV/SIV replication and reservoir establishment, yet how infection and antiretroviral therapy initiation (ARTi) shape the metabolism of CD4⁺ Tcells-main HIV target- in vivo remains poorly defined. Using the SIVmac239 macaque model, we integrated single-cell metabolic profiling (MIST), transcriptomics, lipidomics, genome-scale metabolic modeling, and functional assays to characterize their metabolic remodeling. At peak viremia, CD4⁺ T cells exhibited a marked shutdown of de novo fatty-acid (FA) synthesis, reflected by acetyl-CoA carboxylase-1 (ACC1) downregulation, inhibition of lipid-anabolic reactions, and depletion of membrane phospholipids. This metabolic state was driven by strong type I interferon (IFN-I) responses, and IFN-I exposure was sufficient to suppress ACC1 in vitro . Pharmacologic inhibition of FA synthesis independently enhanced Tcell activation and reduced HIV replication, indicating direct antiviral and immunomodulatory effects. Following ARTi, most metabolic pathways were broadly suppressed, whereas mitochondrial oxidative phosphorylation (OXPHOS) remained elevated. Together, these findings identify IFN-driven FA synthesis shutdown and persistent OXPHOS as defining metabolic features of early HIV/SIV infection and treatment initiation, highlighting these pathways as potential targets to limit viral replication and reservoir formation.