Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia.
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.
Churchill
Melissa J
MJ
Centre for Virology, The Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia. churchil@burnet.edu.au
Wesselingh
Steven L
SL
Cowley
Daniel
D
Pardo
Carlos A
CA
McArthur
Justin C
JC
Brew
Bruce J
BJ
Gorry
Paul R
PR
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
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004279:DNA, Viral; D005904:Glial Fibrillary Acidic Protein; C067980:CD68 antigen, human; D000097382:CD68 Molecule