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Background:  Neural progenitor cells are critical for neurogenesis and response to brain injury. We therefore asked the question whether these cells are a target for HIV-1. We had previously shown that cell cultures of multipotential human fetal brain-derived, nestin (+), neural progenitor cells are permissive for HIV infection, and that differentiation from a nestin (+), gfap (–) neural progenitor state to a gfap (+) astrocytic, but not neuronal phenotype, is associated with increased production of virus. We now report evidence for HIV-1 infection of neural progenitor cells in pediatric brain tissue archived from 1986 to 1995.

Methods:  Immunohistochemical staining for nestin and in situ hybridization to detect HIV-1 RNA were performed on formalin-fixed, paraffin-embedded archival periventricular, basal gangliar, deep frontal, and cerebellar brain tissue from 5 HIV-1⁺ and 1 HIV-uninfected control pediatric patients using polyclonal antiserum raised against human nestin at 1:200 dilution, followed by a ³⁵S-labeled riboprobe representative of more than 90% of the full length HIV-1 genome. After autoradiographic exposure, the slides were developed, counterstained, and analyzed visually.

Results:  Single-label in situ hybridization and immunohistochemical staining were first performed on blocks from all patients to identify those with the highest frequency of HIV⁺ cells and nestin expression. A total of 50 slides were then taken from the 2 patients with the strongest individual HIV-1 and nestin signals. Of the HIV⁺ cells, several from periventricular tissue obtained from a 4-year-old female with neuro-AIDS were double positive for both HIV RNA and nestin.

Conclusions:  This is an ongoing study of archival pediatric brain tissue to identify neural progenitor cells as targets for HIV-1, as suggested by cell culture data. The pathophysiological consequences of HIV-1 infection of neural progenitor cells in the developing pediatric brain must be determined because it is possible that HIV-associated alterations in neural progenitor cell function could contribute to the unique neuropathology of pediatric AIDS, including decreased brain growth, cognitive impairment, and poorly modulated responses to HIV-associated inflammatory brain injury.

Keywords: progenitor; HIV-1; pediatric