AEGiS-15IAC: HIV-1 infection of human brain-derived neural progenitor cells.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

HIV-1 infection of human brain-derived neural progenitor cells.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrA1182)

Schwartz L, Lawrence DM, Seth P, Durham L, Major EO
National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, United States

BACKGROUND: HIV-1 infected adults and children may develop CNS disease, but clinical and pathologic manifestations differ. Microglial cells are productively infected in both, but up to 20% of pediatric subcortical astrocytes may also contain virus, a finding not reported in adults. To investigate this observation, we examined archival HIV-1 pediatric brain, and tested infection of neural progenitors and progenitor-derived astrocytes in a unique culture system derived from human fetal brain.

METHODS: Periventricular tissue was tested for HIV-1 mRNA by in situ hybridization, and for p24 and nestin expression by immunohistochemistry. Cultures of undifferentiated nestin (+) progenitors and progenitor-derived GFAP (+) astrocytes were infected with HIV-1 strains IIIB and PNL4-3, or transfected with pNL4-3 DNA. Supernatant p24 was measured by ELISA. Immunofluorescence for GFAP, nestin and p24 was assessed by confocal microscopy. p24 production was determined in infected progenitors and astrocytes, cells exposed to TNF-α, and in astrocytes differentiated from progenitors immediately after transfection.

RESULTS: Regional colocalization of HIV-1 mRNA and p24 protein with nestin was seen in periventicular tissue. Neural progenitors in culture were successfully infected, or transfected with HIV-1. Differentiation of transfected progenitors towards an astrocytic phenotype increased virus production 5-fold. TNF-α stimulated virus production in both populations.

CONCLUSIONS: Nestin-rich periventricular tissue may harbor HIV-1. In vitro studies support the possibility that human neural progenitor cells can be infected with HIV-1. Differentiation into an astrocytic phenotype is associated with higher viral titer, as is stimulation with TNF-α. Progenitor cells may be an additional reservoir of HIV-1 in the pediatric brain.

Keywords: AEGIS, HIV Infections, HIV-1, Hominidae, Stem Cells, Brain, Astrocytes, Glial Fibrillary Acidic Protein, Microglia, Intermediate Filament Proteins, In Situ Hybridization, Immunohistochemistry, nestin, Humans, Animal, Adult, Child, In Vitro

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TuOrA1182