Persistent productive infection of human glial cells by human immunodeficiency virus (HIV) and by infectious molecular clones of HIV

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Abstract
The nature of the interaction between human immunodeficiency virus (HIV) and human cells of astrocytic origin was studied in vitro with cultured glial cells and intact HIV of infections molecular clones of the virus. Infection of glial cells with intact HIV was characterized by low-level expression of viral transcripts as detected by Northern blotting and in situ hybridization (< 10 copies of HIV RNA per cell), transient virus replication, absence of viral antigens detectable by immunofluorescence, and complete lack of cytopathic effects. However, the HIV-infected glial cells persistently expressed HIV tatIII gene activity as detected by a chloramphenicol acetyltransferase assay, and HIV transcripts could be detected by in situ hybridization in 20 to 30% of cells up to 4 months after infection, suggesting that the lack of cytopathicity in HIV-exposed cells was not due to transient viral infection. To evaluate whether increased expression and replication of HIV in glial cells would have any effect on cell growth and viability, we established HIV-positive glial cells lines by cotransfection of cells with infectious molecular clones of HIV DNA and a selectable marker gene. Three clones were isolated which produced high levels of viral particles, were strongly positive for HIV antigens by immunofluorescence, and contained > 1,000 copies of HIV RNA per cell. These cell lines showed no cytopathic changes (lysis, fusion), and their growth kinetics were similar to HIV- controls, but significant morphological changes were detected (cytoplasmic swelling; increased numbers of rounded, presumably detaching cells). Our results show that astrocytic cells can support a persistent, replicative HIV infection with limited pathogenic effects.