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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

336 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)474-481
Number of pages8
JournalNeurology
Volume44
Issue number3
DOIs
StatePublished - Mar 1994

ASJC Scopus subject areas

  • Clinical Neurology

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