title: Lymphocyte migration through the blood-brain barrier (BBB) in feline immunodeficiency virus infection is significantly influenced by the pre-existence of virus and tumour necrosis factor (TNF)-alpha within the central nervous system (CNS): studies using an in vitro feline BBB model.
abstract: OBJECTIVE
  In human immunodeficiency virus infection, macrophage-tropic and lymphotropic viruses exist in the host. Central nervous system (CNS) infection is an early and ongoing event, important to understand when developing strategies to treat infection. Some knowledge exists on macrophage-tropic virus interactions with the blood-brain barrier (BBB), and the aim of this study was to investigate lymphotropic lentivirus interactions with the BBB.
  
  
  METHODS
  Interactions of the lymphotropic feline immunodeficiency virus (FIV) with an in vitro model of the feline BBB were evaluated in scenarios to mimic in vivo infections.
  
  
  RESULTS
  Cell-free FIV crossed the BBB in very low quantities, and in the presence of tumour necrosis factor (TNF)-alpha, BBB integrity was unaffected. However, cell-associated FIV readily crossed the BBB, but BBB integrity was not significantly altered. Transmigration of uninfected and infected lymphocytes increased in response to TNF-alpha, accompanied by a moderate disruption of barrier integrity and an upregulation of vascular cell adhesion molecule-1 rather than intercellular adhesion molecule-1. Significant enhancement of migration and disruption of BBB tight junctions occurred when infected cells and TNF-alpha were added to the brain side of the BBB and this enhancement was not mediated through additional TNF-alpha production.
  
  
  CONCLUSIONS
  Small quantities of virus in the brain together with TNF-alpha have the potential to stimulate greater cell and viral entry into the CNS and this is likely to involve important factors other than further TNF-alpha production. Lymphotropic lentivirus entry to the CNS is governed by many factors similar to macrophage-tropic strains.
authors.affiliation: University College Dublin, Ireland. nicola.fletcher@ucd.ie
authors.forename: N F
authors.initials: NF
authors.lastname: Fletcher
authors.forename: M G
authors.initials: MG
authors.lastname: Bexiga
authors.forename: D J
authors.initials: DJ
authors.lastname: Brayden
authors.forename: B
authors.initials: B
authors.lastname: Brankin
authors.forename: B J
authors.initials: BJ
authors.lastname: Willett
authors.forename: M J
authors.initials: MJ
authors.lastname: Hosie
authors.forename: J-M
authors.initials: JM
authors.lastname: Jacque
authors.forename: J J
authors.initials: JJ
authors.lastname: Callanan
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001812:Blood-Brain Barrier / Q000503:physiopathology* / Q000821:virology*; D001921:Brain / Q000503:physiopathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology*; D002415:Cats; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D016181:Feline Acquired Immunodeficiency Syndrome / Q000503:physiopathology* / Q000821:virology*; D016089:Immunodeficiency Virus, Feline / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008213:Lymphocyte Activation; D019108:Tight Junctions / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1