title: Transcriptomic analysis of peripheral blood mononuclear cells in rapid progressors in early HIV infection identifies a signature closely correlated with disease progression.
abstract: BACKGROUND
  A substantial percentage (10%-15%) of HIV-infected individuals experience a sharp decline in CD4(+) T-cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) vs chronic progressors (CPs) is critical for early clinical intervention and could provide novel strategies to facilitate vaccine design and immune therapy.
  
  
  METHODS
  mRNA and microRNA (miRNA) expression profiles in the peripheral blood mononuclear cells (PBMCs) of RPs and CPs were investigated at 111 (22) days [mean (SD)] of HIV infection. The association of mRNA and miRNA expression with disease progression was examined by ROC analysis and Kaplan-Meier survival analysis.
  
  
  RESULTS
  Pathway enrichment analysis showed that genes with deregulated expression in RPs were primarily involved in apoptosis pathways. Furthermore, we found that 5 miRNAs (miR-31, -200c, -526a, -99a, and -503) in RPs were significantly decreased compared to those in CPs (P < 0.05). The decreased expression of these miRNAs was associated with a rapid disease of progression of HIV infection with a 94% predictive value as measured by the area under the curve. The upregulated predicted targets from the 5 signature miRNAs and all upregulated genes identified from mRNA microarray analysis converged to the apoptosis pathway. Moreover, overexpression of miR-31 in primary human T cells promoted their survival.
  
  
  CONCLUSIONS
  Our results have identified a distinct transcriptomic signature in PBMCs of RPs and provided novel insights to the pathogenesis of HIV infection.
authors.affiliation: Key Laboratory of AIDS Immunology of Ministry of Health, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Zi-Ning
authors.initials: ZN
authors.lastname: Zhang
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Xu
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Fu
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Jiang
authors.forename: Hua-Lu
authors.initials: HL
authors.lastname: Cui
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics; D016022:Case-Control Studies; D002470:Cell Survival; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000097:blood* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000097:blood; D012333:RNA, Messenger / Q000097:blood; D012372:ROC Curve; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger