biostudies-literatureGuo HNIDDK NIH HHSNIAID NIH HHSNCI NIH HHSDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases423-433https://www.ebi.ac.uk/biostudies/studies/S-EPMC8087183biostudies-literatureUnknown22(4)Individuals infected with human immunodeficiency virus type-1 (HIV-1) show metabolic alterations of CD4⁺ T cells through unclear mechanisms with undefined consequences. We analyzed the transcriptome of CD4⁺ T cells from patients with HIV-1 and revealed that the elevated oxidative phosphorylation (OXPHOS) pathway is associated with poor outcomes. Inhibition of OXPHOS by the US Food and Drug Administration-approved drug metformin, which targets mitochondrial respiratory chain complex-I, suppresses HIV-1 replication in human CD4⁺ T cells and humanized mice. In patients, HIV-1 peak viremia positively correlates with the expression of NLRX1, a mitochondrial innate immune receptor. Quantitative proteomics and metabolic analyses reveal that NLRX1 enhances OXPHOS aNature immunologyMulti-omics analyses reveal that HIV-1 alters CD4⁺ T cell immunometabolism to fuel virus replication.PMC8087183P30 AI050410U19 AI109965P30 CA016086R01 AI127346DK119937R01 AI138797R01 DK119937AI127346R01 AI136990P01 DK094779R01 AI029564Holley-Guthrie EEller LARampanelli ESu LTing JPWang LGarrido CMargolis DMWang QGuo HGhneim KRobb MLCheng LSekaly RPChen XfalseMulti-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 with undefined consequences. We analyzed the transcriptome of CD4⁺ T cells from patients with HIV-1 and revealed that the elevated oxidative phosphorylation (OXPHOS) pathway is associated with poor outcomes. Inhibition of OXPHOS by the US Food and Drug Administration-approved drug metformin, which targets mitochondrial respiratory chain complex-I, suppresses HIV-1 replication in human CD4⁺ T cells and humanized mice. In patients, HIV-1 peak viremia positively correlates with the expression of NLRX1, a mitochondrial innate immune receptor. Quantitative proteomics and metabolic analyses reveal that NLRX1 enhances OXPHOS a2021-01-01T00:00:00Z2021 Apr2026-05-01T12:55:47.445Z2022-02-11T11:19:37.499ZS-EPMC80871833376742710.1038/s41590-021-00898-1