title: Monocytes contribute to differential immune pressure on R5 versus X4 HIV through the adipocytokine visfatin/NAMPT.
abstract: BACKGROUND
  The immune system exerts a diversifying selection pressure on HIV through cellular, humoral and innate mechanisms. This pressure drives viral evolution throughout infection. A better understanding of the natural immune pressure on the virus during infection is warranted, given the clinical interest in eliciting and sustaining an immune response to HIV which can help to control the infection. We undertook to evaluate the potential of the novel HIV-induced, monocyte-derived factor visfatin to modulate viral infection, as part of the innate immune pressure on viral populations.
  
  
  RESULTS
  We show that visfatin is capable of selectively inhibiting infection by R5 HIV strains in macrophages and resting PBMC in vitro, while at the same time remaining indifferent to or even favouring infection by X4 strains. Furthermore, visfatin exerts a direct effect on the relative fitness of R5 versus X4 infections in a viral competition setup. Direct interaction of visfatin with the CCR5 receptor is proposed as a putative mechanism for this differential effect. Possible in vivo relevance of visfatin induction is illustrated by its association with the dominance of CXCR4-using HIV in the plasma.
  
  
  CONCLUSIONS
  As an innate factor produced by monocytes, visfatin is capable of inhibiting infections by R5 but not X4 strains, reflecting a potential selective pressure against R5 viruses.
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: Sébastien
authors.initials: S
authors.lastname: Morin
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Sass
authors.forename: Stephan
authors.initials: S
authors.lastname: Grzesiek
authors.forename: Marc
authors.initials: M
authors.lastname: Vekemans
authors.forename: Eric
authors.initials: E
authors.lastname: Florence
authors.forename: Huyen Thanh Thi
authors.initials: HT
authors.lastname: Tran
authors.forename: Rosina Gabriel
authors.initials: RG
authors.lastname: Imiru
authors.forename: Leo
authors.initials: L
authors.lastname: Heyndrickx
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.forename: Geert
authors.initials: G
authors.lastname: Raes
mesh_terms: D002478:Cells, Cultured; D006678:HIV / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology / Q000821:virology; D054409:Nicotinamide Phosphoribosyltransferase / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism*; D012641:Selection, Genetic; D013045:Species Specificity; D020349:Surface Plasmon Resonance; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics / Q000276:immunology
chemical_list: D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D054409:Nicotinamide Phosphoribosyltransferase