title: Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia.
abstract: Astrocyte infection with human immunodeficiency virus (HIV) is considered rare, so astrocytes are thought to play a secondary role in HIV neuropathogenesis. By combining double immunohistochemistry, laser capture microdissection, and highly sensitive multiplexed polymerase chain reaction to detect HIV DNA in single astrocytes in vivo, we showed that astrocyte infection is extensive in subjects with HIV-associated dementia, occurring in up to 19% of GFAP+ cells. In addition, astrocyte infection frequency correlated with the severity of neuropathological changes and proximity to perivascular macrophages. Our data indicate that astrocytes can be extensively infected with HIV, and suggest an important role for HIV-infected astrocytes in HIV neuropathogenesis.
authors.affiliation: Centre for Virology, The Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia. churchil@burnet.edu.au
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Churchill
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wesselingh
authors.forename: Daniel
authors.initials: D
authors.lastname: Cowley
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pardo
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Brew
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
mesh_terms: D015526:AIDS Dementia Complex / Q000473:pathology / Q000821:virology*; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000821:virology*; D004279:DNA, Viral; D018792:Encephalitis, Viral / Q000473:pathology / Q000821:virology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006678:HIV / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008264:Macrophages / Q000502:physiology; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009474:Neurons / Q000821:virology; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004279:DNA, Viral; D005904:Glial Fibrillary Acidic Protein; C067980:CD68 antigen, human; D000097382:CD68 Molecule