title: Transcriptome analysis of monocyte-HIV interactions.
abstract: BACKGROUND
  During HIV infection and/or antiretroviral therapy (ART), monocytes and macrophages exhibit a wide range of dysfunctions which contribute significantly to HIV pathogenesis and therapy-associated complications. Nevertheless, the molecular components which contribute to these dysfunctions remain elusive. We therefore applied a parallel approach of genome-wide microarray analysis and focused gene expression profiling on monocytes from patients in different stages of HIV infection and/or ART to further characterise these dysfunctions.
  
  
  RESULTS
  Processes involved in apoptosis, cell cycle, lipid metabolism, proteasome function, protein trafficking and transcriptional regulation were identified as areas of monocyte dysfunction during HIV infection. Individual genes potentially contributing to these monocyte dysfunctions included several novel factors. One of these is the adipocytokine NAMPT/visfatin, which we show to be capable of inhibiting HIV at an early step in its life cycle. Roughly half of all genes identified were restored to control levels under ART, while the others represented a persistent dysregulation. Additionally, several candidate biomarkers (in particular CCL1 and CYP2C19) for the development of the abacavir hypersensitivity reaction were suggested.
  
  
  CONCLUSIONS
  Previously described areas of monocyte dysfunction during HIV infection were confirmed, and novel themes were identified. Furthermore, individual genes associated with these dysfunctions and with ART-associated disorders were pinpointed. These genes form a useful basis for further functional studies concerning the contribution of monocytes/macrophages to HIV pathogenesis. One such gene, NAMPT/visfatin, represents a possible novel restriction factor for HIV.
authors.affiliation: Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium. rvdbergh@vub.ac.be
authors.forename: Rafael
authors.initials: R
authors.lastname: Van den Bergh
authors.forename: Eric
authors.initials: E
authors.lastname: Florence
authors.forename: Erika
authors.initials: E
authors.lastname: Vlieghe
authors.forename: Tom
authors.initials: T
authors.lastname: Boonefaes
authors.forename: Johan
authors.initials: J
authors.lastname: Grooten
authors.forename: Erica
authors.initials: E
authors.lastname: Houthuys
authors.forename: Huyen Thi Thanh
authors.initials: HT
authors.lastname: Tran
authors.forename: Youssef
authors.initials: Y
authors.lastname: Gali
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.forename: Geert
authors.initials: G
authors.lastname: Raes
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology* / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D009000:Monocytes / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D019380:Anti-HIV Agents