Premium
Localization of HIV‐1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry
Author(s) -
Takahashi Kiyomi,
Wesselingh Steven L.,
Griffin Diane E.,
McArthur Justin C.,
Johnson Richard T.,
Glass Jonathan D.
Publication year - 1996
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410390606
Subject(s) - microglia , in situ hybridization , immunocytochemistry , dementia , biology , polymerase chain reaction , immunology , virology , pathology , neuroglia , medicine , central nervous system , disease , neuroscience , inflammation , gene , gene expression , genetics
Human immunodeficiency virus type 1 (HIV‐1) infects the brains of a majority of patients with the acquired immunodeficiency syndrome (AIDS), and has been linked to the development of a progressive dementia termed “HIV‐associated dementia.” This disorder results in severe cognitive, behavioral, and motor deficits. Despite this neurological dysfunction, HIV‐1 infection of brain cells does not occur significantly in neurons, astrocytes, or oligodendrocytes, but is restricted to brain macrophages and microglia. To identify possible low‐level or latent infection of other brain cells, we combined the techniques of the polymerase chain reaction with in situ hybridization for the detection of HIV DNA, and used immunocytochemistry to identify the HIV‐expressing cells. In the 21 adult brains studied (15 AIDS and 6 seronegative control brains), we found that polymerase chain reaction/in situ hybridization was both sensitive and specific for identifying HIV‐infected cells. In all brains, the majority of infected cells were macrophages and microglia. In several brains, however, a substantial minority of cells harboring HIV DNA were identified as astrocytes. Neurons, oligodendrocytes, and endothelial cells were not infected with HIV, even in cases with HIV‐associated dementia. These findings confirm previous data regarding the importance of macrophage/microglial infection, and essentially exclude neuronal infection in pathogenetic models of HIV‐associated neurological disease. These data also demonstrate that latent or low‐level infection of astrocytes occurs in AIDS, a finding that may be of importance in understanding HIV neuropathogenesis.