Analysis of nonproductive human immunodeficiency virus type 1 infection of human fetal dorsal root ganglia glial cells.
Direct infection of glia by human immunodeficiency virus type 1 (HIV-1) has been suggested as one of several mechanisms responsible for the severe neurologic complications observed in both neonates and adults with the acquired immunodeficiency syndrome. We have demonstrated by protein immunoblotting analysis that HIV-1 infection of human fetal glial cells isolated from the dorsal root ganglia (DRG) of the developing human peripheral nervous system results in viral gag antigen expression with little, if any, detectable env gene products. No cytopathogenicity was evident in the infected cell population. Blot hybridization analyses indicate transient expression of the HIV-1 genome with maximum levels of virus-specific RNA being observed between 2 and 3 days postinfection and decreasing below the limits of detection by 16 days postinfection. To determine whether infection of the human fetal DRG glial cell population culminates in the production and release of infectious HIV-1, cocultivation and reverse transcriptase assays were performed. Direct assay of HIV-1-infected neural cell supernatants as well as exposure of permissive SupT1 cells to these HIV-1-infected neural cell supernatants resulted in no demonstrable reverse transcriptase activity in either the HIV-1-infected DRG glial cell supernatants or the SupT1 cell supernatants. Although transmission electron microscopy analyses have suggested the absence of intracellular viral particles, highly electron-dense inclusions in the cytoplasm of HIV-1-infected DRG glial cells were observed. The nature of the intracellular cytoplasmic inclusions is under current investigation. Cumulatively, these data suggest that the interaction of HIV-1 with human fetal DRG neural cells results in transient expression of the HIV genome culminating in a nonproductive infection.
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey 17033.
C
C
Kunsch
B
B
Wigdahl
D002478:Cells, Cultured; D005333:Fetus; D005727:Ganglia, Spinal / Q000382:microbiology* / Q000648:ultrastructure; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015488:HIV Antigens / Q000096:biosynthesis / Q000235:genetics; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000254:growth & development* / Q000648:ultrastructure; D006801:Humans; D015151:Immunoblotting; D009457:Neuroglia / Q000382:microbiology* / Q000648:ultrastructure; D012367:RNA, Viral / Q000032:analysis; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism
D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D012367:RNA, Viral; D014758:Viral Core Proteins; D012194:RNA-Directed DNA Polymerase