title: HIV infection and antiretroviral therapy have divergent effects on mitochondria in adipose tissue.
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.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1403, USA. cmorse@mail.nih.gov
authors.forename: Caryn G
authors.initials: CG
authors.lastname: Morse
authors.forename: Joachim G
authors.initials: JG
authors.lastname: Voss
authors.forename: Goran
authors.initials: G
authors.lastname: Rakocevic
authors.forename: Mary
authors.initials: M
authors.lastname: McLaughlin
authors.forename: Carol L
authors.initials: CL
authors.lastname: Vinton
authors.forename: Charles
authors.initials: C
authors.lastname: Huber
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Da Wei
authors.initials: da W
authors.lastname: Huang
authors.forename: Carolea
authors.initials: C
authors.lastname: Logun
authors.forename: Robert L
authors.initials: RL
authors.lastname: Danner
authors.forename: Zoila G
authors.initials: ZG
authors.lastname: Rangel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Munson
authors.forename: Jan M
authors.initials: JM
authors.lastname: Orenstein
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Rushing
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Marinos C
authors.initials: MC
authors.lastname: Dalakas
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects*; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial