Background:  HIV-1 infection of the central nervous system in infants and children is associated with impaired brain growth, developmental delays, and deficits in memory and language development. Neural progenitor cells are critical for neurogenesis and support of maturing neurons. We have shown previously in cell culture that human, nestin⁺ neural progenitor are permissive for HIV-1 infection, and in tissue by in situ hybridization, that HIV-1 was present in a nestin⁺ periventricular cell from archived pediatric brain. We now report HIV-1 gag sequences in DNA extracted from nestin⁺ neural progenitors excised by laser capture microdissection from paraffin-embedded pediatric hippocampal tissue.

Methods:  Nestin⁺ neural progenitors in formalin-fixed, paraffin-embedded archival hippocampal and periventricular tissue from a 19-month-old female with neuroAIDS, and 2 uninfected infants were identified by tyramide signal-amplified fluorescence immunohistochemistry. After cell capture by laser microdissection, DNA was extracted, polymerase chain reaction (PCR) amplified, visualized by gel electrophoresis, and sequenced. Results were displayed and identified using a basic local alignment search tool (BLAST).

Results:  Nestin⁺ cells were identified and harvested from hippocampal and periventricular tissue. The HIV-1 gag sequence was identified in DNA extracted from nestin⁺ cells dissected from the hippocampus of the HIV-1-infected patient. No such sequences were identified in negative control cells from culture or archived human tissue from uninfected infants.

Conclusions:  HIV-1 gag DNA was found in nestin⁺ cells harvested from archived hippocampal tissue from a vertically infected child with neuroAIDS. This finding, along with our previously reported cell culture and periventricular in situ hybridization data, provides strong evidence that neural progenitors are a target for HIV-1 infection in vivo. HIV-1-infected neural progenitors have now been found in 2 anatomic regions of the pediatric brain, raising the possibility that HIV-1-infected neural progenitors in the developing brain may migrate from the periventricular region to the hippocampus. Because neural progenitors are critical for brain development and response to injury, HIV-1 infection of progenitors within the hippocampus might adversely affect those functions, thereby contributing to the developmental delays, and the cognitive, language, and memory impairments seen in HIV-1-infected infants and children.