Multi-omics analyses reveal that HIV-1 alters CD4+ T cell immunometabolism to fuel virus replication

Individuals infected with human immunodeficiency virus type-1 (HIV-1) show metabolic alterations of CD4+ T cells through unclear mechanisms undefined consequences. We analyzed the transcriptome from patients HIV-1 and revealed that elevated oxidative phosphorylation (OXPHOS) pathway is associated poor outcomes. Inhibition OXPHOS by US Food Drug Administration–approved drug metformin, which targets mitochondrial respiratory chain complex-I, suppresses replication in humanized mice. In patients, peak viremia positively correlates expression NLRX1, a innate immune receptor. Quantitative proteomics analyses reveal NLRX1 enhances glycolysis during HIV-1-infection to promote viral replication. At mechanistic level, HIV infection induces association protein FASTKD5 complex components. This study uncovers as target for therapy. Ting colleagues use multi-omics examine undergone following infection. They describe changes lead phosphorylation, which, if inhibited, leads suppression