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

ABSTRACT: 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 a

SUBMITTER: Guo H 

PROVIDER: S-EPMC8087183 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature