title: Differential type 1 interferon-regulated gene expression in the brain during AIDS: interactions with viral diversity and neurovirulence.
abstract: The lentiviruses, human and feline immunodeficiency viruses (HIV-1 and FIV, respectively), infect the brain and cause neurovirulence, evident as neuronal injury, inflammation, and neurobehavioral abnormalities with diminished survival. Herein, different lentivirus infections in conjunction with neural cell viability were investigated, concentrating on type 1 interferon-regulated pathways. Transcriptomic network analyses showed a preponderance of genes involved in type 1 interferon signaling, which was verified by increased expression of the type 1 interferon-associated genes, Mx1 and CD317, in brains from HIV-infected persons (P<0.05). Leukocytes infected with different strains of FIV or HIV-1 showed differential Mx1 and CD317 expression (P<0.05). In vivo studies of animals infected with the FIV strains, FIV(ch) or FIV(ncsu), revealed that FIV(ch)-infected animals displayed deficits in memory and motor speed compared with the FIV(ncsu)- and mock-infected groups (P<0.05). TNF-α, IL-1β, and CD40 expression was increased in the brains of FIV(ch)-infected animals; conversely, Mx1 and CD317 transcript levels were increased in the brains of FIV(ncsu)-infected animals, principally in microglia (P<0.05). Gliosis and neuronal loss were evident among FIV(ch)-infected animals compared with mock- and FIV(ncsu)-infected animals (P<0.05). Lentiviral infections induce type 1 interferon-regulated gene expression in microglia in a viral diversity-dependent manner, representing a mechanism by which immune responses might be exploited to limit neurovirulence.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Polyak
authors.forename: Pornpun
authors.initials: P
authors.lastname: Vivithanaporn
authors.forename: Ferdinand G
authors.initials: FG
authors.lastname: Maingat
authors.forename: John G
authors.initials: JG
authors.lastname: Walsh
authors.forename: William
authors.initials: W
authors.lastname: Branton
authors.forename: Eric A
authors.initials: EA
authors.lastname: Cohen
authors.forename: Rick
authors.initials: R
authors.lastname: Meeker
authors.forename: Christopher
authors.initials: C
authors.lastname: Power
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000821:virology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002415:Cats; D002460:Cell Line; D002478:Cells, Cultured; D016181:Feline Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000821:virology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009043:Motor Activity / Q000276:immunology; D064547:Myxovirus Resistance Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014774:Virulence / Q000276:immunology; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D019204:GTP-Binding Proteins; D007370:Interferon Type I; D064547:Myxovirus Resistance Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2
keywords: BST-2; CD317; FIV; HIV-1; microglia; tetherin; type 1 interferon