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March 01, 1994; 44 (3 Part 1) Articles

Overexpression of nef as a marker for restricted HIV‐1 infection of astrocytes in postmortem pediatric central nervous tissues

Y. Saito, L. R. Sharer, L. G. Epstein, J. Michaels, M. Mintz, M. Louder, K. Golding, T. A. Cvetkovich, B. M. Blumberg
First published March 1, 1994, DOI: https://doi.org/10.1212/WNL.44.3_Part_1.474
Y. Saito
MD
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L. R. Sharer
MD
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L. G. Epstein
MD
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J. Michaels
MD
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M. Mintz
MD
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M. Louder
MD
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K. Golding
BA
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T. A. Cvetkovich
MD
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B. M. Blumberg
PhD
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Citation
Overexpression of nef as a marker for restricted HIV‐1 infection of astrocytes in postmortem pediatric central nervous tissues
Y. Saito, L. R. Sharer, L. G. Epstein, J. Michaels, M. Mintz, M. Louder, K. Golding, T. A. Cvetkovich, B. M. Blumberg
Neurology Mar 1994, 44 (3 Part 1) 474; DOI: 10.1212/WNL.44.3_Part_1.474

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Abstract

In previous studies, using polymerase chain reaction amplification of HIV-1 genes directly from pathologic tissues of children who died with AIDS encephalopathy, we showed that the reading frame of the HIV-1 regulatory nef gene is open, suggesting that the nef protein was expressed. We now show, using immunocytoehemistry and in situ hybridization with nef-specific probes in postmortem pediatric CNS tissues, that nef mRNA and protein are present in up to 20% of astrocytes in tissue sections selected for extensive histopathology. By contrast, HIV-1 structural proteins such as gag and their coding mRNAs are present in multinucleated giant cells that harbor productive infection and are the hallmark of HIV-1 infection in the CNS. These findings are consistent with the nonproductive infection of glial cells observed in vitro, and imply that HIV-1 infection of astrocytes is restricted to early regulatory gene products, of which nef is the best target as it is expressed at high levels and is membrane-anchored. In developing central nervous tissues of children, restricted and latent HIV-1 infection of astrocytes may be extensive and contribute significantly to HIV-1 neuropathogenesis.

  • © 1994 by the American Academy of Neurology

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