Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation

• Published in: PloS one 2020-04, Vol.15 (4), p.e0231761
• Main Authors: Gangcuangco, Louie Mar A, Mitchell, Brooks I, Siriwardhana, Chathura, Kohorn, Lindsay B, Chew, Glen M, Bowler, Scott, Kallianpur, Kalpana J, Chow, Dominic C, Ndhlovu, Lishomwa C, Gerschenson, Mariana, Shikuma, Cecilia M
• Format: Article
• Language: English
• Subjects: Adenosine triphosphate; Age; Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral therapy; Biology and Life Sciences; Blood; CD14 antigen; CD16 antigen; CD4 antigen; CD4-CD8 Ratio; CD8 antigen; Cell activation; Chronic fatigue syndrome; Cross-Sectional Studies; Cytochrome; Cytochrome-c oxidase; Cytochromes; Dehydrogenases; Deoxyribonucleic acid; Didanosine; Disease; DNA; Enzymes; Exhaustion; Female; Flow cytometry; Hawaii; HIV; HIV Infections - diagnosis; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - isolation & purification; Host-Pathogen Interactions - immunology; Human immunodeficiency virus; Humans; Immunoassay; Immunoassays; Inflammation; Leukocytes (mononuclear); Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Level (quantity); Lymphocyte Activation; Lymphocytes T; Male; Medicine and Health Sciences; Middle Aged; Minority & ethnic groups; Mitochondria; Mitochondria - immunology; Mitochondria - metabolism; Mitochondrial DNA; Monocytes; Mutation; NADH; NADH dehydrogenase; Nicotinamide adenine dinucleotide; Optical density; Oxidative Phosphorylation; Peripheral blood mononuclear cells; Phosphorylation; Protein X; Proteins; Respiration; Ribonucleic acid; RNA; RNA, Viral - isolation & purification; Senescence; Severity of Illness Index; Zidovudine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0231761

Cellular immunometabolism among people living with HIV (PLWH) on antiretroviral therapy (ART) remains under investigated. We assessed the relationships between mitochondrial oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) and blood parameters associated with HIV immune dysregulation. PLWH ≥40 years old and on stable ART ≥3 months were enrolled (N = 149). OXPHOS complex I (CI, NADH dehydrogenase) and complex IV (CIV, cytochrome c oxidase) protein levels in PBMCs were quantified using immunoassays. Monocyte subsets and markers of T-cell activation, senescence, and exhaustion were measured on PBMC by flow cytometry. Plasma inflammatory mediators were quantified using a multiplex assay. HIV-uninfected group (N = 44) of similar age, gender, and ethnicity had available OXPHOS levels. PLWH had a median age of 51 years. Majority were male (88.6%), Caucasian (57.7%), and with undetectable plasma HIV RNA