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American Journal of Pathology, Vol 142, 25-31, Copyright © 1993 by American Society for Investigative Pathology

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Detection of a neuron-specific 9.0-kb transcript which shares homology with antisense transcripts of HIV-1 gag gene in patients with and without HIV-1 infection

TC Wu, MD Kanayama, RH Hruban, W Whitehead and NB Raj
Department of Pathology, Johns Hopkins Medical Institution, Baltimore, Maryland.

The pathogenesis of the neurologic abnormalities associated with the acquired immune deficiency syndrome (AIDS) is poorly understood. Although human immunodeficiency virus type 1 (HIV-1) transcripts have been detected in endothelial cells and macrophages of the central nervous system in patients with AIDS, infection of neuronal cells by HIV-1 has not been established. The purpose of this study was to localize HIV-1 transcripts in the central nervous system. 3H and digoxigenin-UTP-labeled riboprobes generated from a 942-bp fragment of DNA from the 5' end of the HIV-1 gag sequence were used for in situ hybridization. The antisense riboprobe hybridized to lymphoid cells in the sections of kidney and spleen obtained from patients with AIDS, as well as to the HIV-1-infected A3.01 cell line. The control sense probe did not hybridize to these same cells. In contrast, no detectable hybridization was observed to neuronal cells when the antisense probe was applied to sections of brain obtained from patients with and without AIDS. To our surprise, however, specific hybridization was observed to neuronal cells when the control sense probe was applied. This hybridization with the control sense probe was seen in both patients with and without HIV-1 infection. Northern blot analysis confirmed the in situ hybridization results; a unique 9.0-kb transcript was detected exclusively in brain tissue. These data suggest that there is a neuron-specific 9.0-kb transcript that shares extensive homology with antisense gag HIV-1 sequences and that this transcript is expressed in neuronal cells of both HIV-1-infected and noninfected individuals. The biological significance of this 9.0-kb transcript is unknown, but it may play an important role in the interactions of HIV-1 with neuronal cells.