Children born with congenital HIV-1 infection show abnormalities in behavior, cognition, and neurodevelopment. These clinical observations have been correlated with pathological changes in the CNS. The main hypothesis to be tested is that HIV-1 exposure leads directly to alterations in astroglial and neuronal metabolism. Such alterations serve as the biochemical correlates of developmental aberrations in the CNS. In vitro studies have demonstrated HIV-1 infection in astrocytes. However, these studies have not correlated with any in vivo studies of specific biochemical dysfunctions. A series of in vivo and in vitro experiments are planned that will elucidate cell-type specific responses to HIV-1 infection. Glial fibrillary acidic protein (GFAP), a protein specific to astrocytes, will be used as the measure of astrocytic responses and the 66 KD neurofilament protein (NF-66) for neuronal responses. The effect of HIV-1 infection on the specific markers for these two cell types will be investigated in three systems shared by other components of the Program Project. Double labelling methods (double immunocytochemistry or immunocytochemistry) combined with in situ hybridization will be used to simultaneously visualize the localization of HSP-70, GFAP, NF-66, or viral components, proteins or mRNAs.
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