title: A plasma microRNA signature of acute lentiviral infection:  biomarkers of central nervous system disease.
abstract: OBJECTIVE
  Plasma microRNAs (miRNAs) are modulated during disease and are emerging biomarkers; they have not been characterized in HIV infection. Using our macaque/simian immunodeficiency virus (SIV) model of HIV, we sought to identify a plasma miRNA profile of acute lentiviral infection, evaluate its relationship with known cellular and viral determinants of lentivirus-associated central nervous system (CNS) disease, and explore the potential of miRNAs to predict CNS disease.
  
  
  METHODS
  Plasma samples were obtained before inoculation and 10 days after inoculation from SIV-infected macaques.
  
  
  METHODS
  Plasma miRNA expression profiles were determined by TaqMan low-density array for six individuals. miRNA expression was compared with levels of cytokines, virus, and plasma platelet count. miRNA results were confirmed by single miRNA-specific assays for 10 macaques. Nineteen individuals were used to validate a disease prediction test.
  
  
  RESULTS
  A 45-miRNA signature of acute infection (differential expression with P < 0.05 after multiple comparison correction) classified plasma as infected or not. Several differentially expressed miRNAs correlated with CNS disease-associated cytokines interleukin-6 and CCL2 and included predicted and/or validated regulators of the corresponding mRNAs. miRNAs tracked with viral load and platelet count were also predictors of CNS disease. At least six miRNAs were significantly differentially expressed in individuals with severe versus no CNS disease; in an unweighted expression test, they predicted CNS disease.
  
  
  CONCLUSIONS
  Acute-phase differential expression of plasma miRNAs predicts CNS disease and suggests that CNS damage or predisposition to disease progression begins in the earliest phase of infection. Plasma miRNAs should be investigated further as leading indicators of HIV diseases as early as acute infection.
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. kwitwer1@jhmi.edu
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Witwer
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sarbanes
authors.forename: Jonathan
authors.initials: J
authors.lastname: Liu
authors.forename: Janice E
authors.initials: JE
authors.lastname: Clements
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D020805:Central Nervous System Viral Diseases / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000097:blood*; D008251:Macaca; D035683:MicroRNAs / Q000097:blood*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000097:blood; D012367:RNA, Viral / Q000097:blood*; D017423:Sequence Analysis, RNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D014779:Virus Replication
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D015850:Interleukin-6; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral