title: Human immunodeficiency virus type 1 infection of human brain-derived progenitor cells.
abstract: Although cells of monocytic lineage are the primary source of human immunodeficiency virus type 1 (HIV-1) in the brain, other cell types in the central nervous system, including astrocytes, can harbor a latent or persistent HIV-1 infection. In the present study, we examined whether immature, multipotential human brain-derived progenitor cells (nestin positive) are also permissive for infection. When exposed to IIIB and NL4-3 strains of HIV-1, progenitor cells and progenitor-derived astrocytes became infected, with peak p24 levels of 100 to 500 pg/ml at 3 to 6 days postinfection. After 10 days, virus production was undetectable but could be stimulated by the addition of tumor necrosis factor alpha (TNF-alpha). To bypass limitations to receptor entry, we compared the fate of infection in these cell populations by transfection with the infectious HIV-1 clone, pNL4-3. Again, transfected progenitors and astrocytes produced virus for 7 days but diminished to low levels beyond 8 days posttransfection. During the nonproductive phase, TNF-alpha stimulated virus production from progenitors as late as 5 weeks posttransfection. Astrocytes produced 5- to 20-fold more infectious virus (27 ng of p24/10(6) cells) than progenitors at the peak of 3 days posttransfection. Differentiation of infected progenitors toward an astrocyte phenotype increased virus production to levels consistent with infected astrocytes, suggesting a phenotypic difference in viral replication. Using this cell culture system of multipotential human brain-derived progenitor cells, we provide evidence that progenitor cells may be a reservoir for HIV-1 in the brains of AIDS patients.
authors.affiliation: Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Diane M P
authors.initials: DM
authors.lastname: Lawrence
authors.forename: Linda C
authors.initials: LC
authors.lastname: Durham
authors.forename: Lynnae
authors.initials: L
authors.lastname: Schwartz
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.forename: Eugene O
authors.initials: EO
authors.lastname: Major
mesh_terms: D001253:Astrocytes / Q000821:virology; D001921:Brain / Q000166:cytology / Q000821:virology*; D002478:Cells, Cultured; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D009474:Neurons / Q000821:virology; D019718:Receptors, CXCR4 / Q000378:metabolism; D013234:Stem Cells / Q000821:virology*; D014162:Transfection
chemical_list: D019718:Receptors, CXCR4