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ABSTRACT: Background
Although human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and function, comprehensive evaluations of their effects on mitochondria in muscle, adipose tissue, and blood cells are limited.Methods
Mitochondrial DNA quantification, mitochondrial genome sequencing, and gene expression analysis were performed on muscle, adipose tissue, and peripheral blood mononuclear cell (PBMC) samples from untreated HIV-positive patients, HIV-positive patients receiving nucleoside reverse transcriptase inhibitor (NRTI)-based ART, and HIV-negative controls.Results
The adipose tissue mtDNA/nuclear DNA (nDNA) ratio was increased in untreated HIV-infected patients (ratio, 353) and decreased in those receiving ART (ratio, 162) compared with controls (ratio, 255; P < .05 for both comparisons); the difference between the 2 HIV-infected groups was also significant (P = .002). In HIV-infected participants, mtDNA/nDNA in adipose tissue correlated with the level of activation (CD38+ /HLA-DR+) for CD4+ and CD8+ lymphocytes. No significant differences in mtDNA content were noted in muscle or PMBCs among groups. Exploratory DNA microarray analysis identified differential gene expression between patient groups, including a subset of adipose tissue genes.Conclusions
HIV infection and ART have opposing effects on mtDNA content in adipose tissue; immune activation may mediate the effects of HIV, whereas NRTIs likely mediate the effects of ART.
SUBMITTER: Morse CG
PROVIDER: S-EPMC3357134 | biostudies-literature | 2012 Jun
REPOSITORIES: biostudies-literature

Morse Caryn G CG Voss Joachim G JG Rakocevic Goran G McLaughlin Mary M Vinton Carol L CL Huber Charles C Hu Xiaojun X Yang Jun J Huang Da Wei da W Logun Carolea C Danner Robert L RL Rangel Zoila G ZG Munson Peter J PJ Orenstein Jan M JM Rushing Elisabeth J EJ Lempicki Richard A RA Dalakas Marinos C MC Kovacs Joseph A JA
The Journal of infectious diseases 20120403 12
<h4>Background</h4>Although human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and function, comprehensive evaluations of their effects on mitochondria in muscle, adipose tissue, and blood cells are limited.<h4>Methods</h4>Mitochondrial DNA quantification, mitochondrial genome sequencing, and gene expression analysis were performed on muscle, adipose tissue, and peripheral blood mononuclear cell (PBMC) samples from untreated HIV ...[more]