title: Lack of evidence for mtDNA as a biomarker of innate immune activation in HIV infection.
abstract: Many human immunodeficiency virus (HIV) infected individuals suffer from persistent immune activation. Chronic inflammation and immune dysregulation have been associated with an increased risk of age-related diseases even among patients on highly active antiretroviral therapy. The factors leading to immune activation are complex, but have been hypothesized to include persistent viral replication with cellular death as well as microbial translocation across the gastrointestinal tract. Both processes may trigger innate immune responses since many native molecules released from dying cells are similar in structure to pathogen associated molecular patterns. These damage associated molecular patterns include mitochondrial DNA and formylated peptides. We hypothesized that circulating mitochondrial nucleic acid could serve as a biomarker for HIV-associated cell death and drive innate immune activation in infected individuals. We developed a quantitative polymerase chain reaction assay for plasma mitochondrial DNA and validated it on normal blood donors. We then measured mitochondrial DNA levels in acute and chronic HIV infection. While the assay proved to be accurate with a robust dynamic range, we did not find a significant association between HIV disease status and circulating mitochondrial DNA. We did, however, observe a negative correlation between age and plasma mitochondrial DNA levels in individuals with well-controlled HIV.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America. alauring med.umich.edu
authors.forename: Adam S
authors.initials: AS
authors.lastname: Lauring
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Michael
authors.initials: M
authors.lastname: Busch
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood* / Q000378:metabolism; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000502:physiology*; D008297:Male; D016133:Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial