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HIV-1 infection of subcortical astrocytes in the pediatric central nervous system

Section on Molecular Therapeutics (Drs. Tornatore and Major), Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; the Department of Pathology (Dr. Chandra), Children's National Medical Center, Washington, DC; and the Department of Neurology (Dr. Berger), University of Miami School of Medicine, Miami, FL.

Early reports of pediatric HIV-1-associated neuropathology described the presence of viral particles in some astrocytes, implicating direct infection of the immature nervous system as a contributing factor to the observed neuropathology. Several recent reports suggest that in those astrocytes infected with HIV-1, the level of antigenic expression of the proviral genome is below the sensitivity limits of conventional histochemical techniques. Identification of these astrocytes would instead require the use of a highly sensitive radiolabeled DNA or RNA probe for in situ hybridization to detect the persistent viral nucleic acids. To test this hypothesis, we examined autopsy tissue from 12 infants and children with AIDS-associated encephalopathy for the presence of HIV-1-infected astrocytes using combined isotopic in situ hybridization for the detection of viral-specific nucleic acids and immunohistochemistry for the identification of astrocytes. We detected HIV-1 nucleic acids in astrocytes in subcortical white matter from four pediatric patients with moderate to extensive leukoencephalitis. While gp41 was detectable only on macrophages and multinucleated giant cells, HIV-1 Nef protein was present in cells morphologically identified as astrocytes in two of these patients, further suggesting that HIV-1 establishes a persistent rather than a productive infection in astrocytes. Subcortical astrocytes may therefore be an unrecognized reservoir for HIV-1 in the developing nervous system of some children with AIDS-associated leukoencephalitis.

Address correspondence and reprint requests to Dr. Carlo Tornatore, Section on Molecular Therapeutics, Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Received May 13, 1993. Accepted for publication in final form August 20, 1993

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