HIV-1 INFECTION OF SUBCORTICAL ASTROCYTES IN THE PEDIATRIC CENTRAL-NERVOUS-SYSTEM

Early reports of pediatric HIV-1-associated neuropathology described t he presence of viral particles in some astrocytes, implicating direct infection of the immature nervous system as a contributing factor to t he observed neuropathology. Several recent reports suggest that in tho se astrocytes infected with HIV-1, the level of antigenic expression o f the proviral genome is below the sensitivity limits of conventional histochemical techniques. Identification of these astrocytes would ins tead require the use of a highly sensitive radiolabeled DNA or RNA pro be for in situ hybridization to detect the persistent viral nucleic ac ids. To test this hypothesis, we examined autopsy tissue from 12 infan ts and children with AIDS-associated encephalopathy for the presence o f HIV-1-infected astrocytes using combined isotopic in situ hybridizat ion for the detection of viral-specific nucleic acids and immunohistoc hemistry for the identification of astrocytes. We detected HIV-1 nucle ic acids m astrocytes m subcortical white matter from four pediatric p atients with moderate to extensive leukoencephalitis. While gp41 was d etectable only on macrophages and multinucleated giant cells, HIV-1 Ne f protein was present in cells morphologically identified as astrocyte s in two of these patients, further suggesting that HIV-1 establishes a persistent rather than a productive infection in astrocytes. Subcort ical astrocytes may therefore be an unrecognized reservoir for HIV-1 i n the developing nervous system of some children with AIDS-associated leukoencephalitis.