Overexpression of nef as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues.
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 immunocytochemistry 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.
Saito
Y
Y
Department of Neurology, University of Rochester Medical Center, NY 14642.
Sharer
L R
LR
Epstein
L G
LG
Michaels
J
J
Mintz
M
M
Louder
M
M
Golding
K
K
Cvetkovich
T A
TA
Blumberg
B M
BM
D000368:Aged; D001253:Astrocytes / Q000382:microbiology*; D001921:Brain / Q000382:microbiology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015967:Gene Expression Regulation, Viral; D015754:Genes, nef; D015658:HIV Infections / Q000382:microbiology* / Q000473:pathology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D008297:Male; D008875:Middle Aged; D013116:Spinal Cord / Q000382:microbiology* / Q000473:pathology; D013997:Time Factors