title: Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells.
abstract: BACKGROUND
  Microglia are one of the main cell types to be productively infected by HIV-1 in the central nervous system (CNS). Leukotriene B4 (LTB4) and cysteinyl-leukotrienes such as LTC4 are some of the proinflammatory molecules produced in infected individuals that contribute to neuroinflammation. We therefore sought to investigate the role of leukotrienes (LTs) in HIV-1 infection of microglial cells.
  
  
  METHODS
  To evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis) were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2) or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  We report in this study that virus replication is reduced upon treatment of MDMis with LTB4 and LTC4. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5) surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C.
  
  
  CONCLUSIONS
  These data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS.
authors.affiliation: Centre de Recherche en Infectiologie, RC709, Centre Hospitalier Universitaire de Québec-CHUL, 2705 Boul, Laurier, Québec, QC G1V 4G2, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bertin
authors.forename: Corinne
authors.initials: C
authors.lastname: Barat
authors.forename: Dave
authors.initials: D
authors.lastname: Bélanger
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015658:HIV Infections / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000821:virology*; D013373:Substance P / Q000378:metabolism; D014162:Transfection
chemical_list: D007975:Leukotriene B4; D013373:Substance P