Internalization of exogenous human immunodeficiency virus-1 protein, Tat, by KG-1 oligodendroglioma cells followed by stimulation of DNA replication initiated at the JC virus origin.
JC virus (JCV) is the etiological agent of an opportunistic brain infection, progressive multifocal leukoencephalopathy (PML), in AIDS. PML is fatal in approximately 4% of HIV-infected individuals, and although the overall incidence has fallen due to highly aggressive antiretroviral therapy (HAART), this percent has remained steady. It has been shown that the Tat protein of human immunodeficiency virus-1 (HIV-1) interacts in cells with cellular protein Puralpha. This interaction can stimulate transcription of both HIV-1 and JCV genes. HIV-1, however, infects primarily microglia and astrocytes in the brain, whereas JCV infects primarily oligodendrocytes. Although HIV-1 has been shown capable of infecting oligodendrocytes in vitro (Albright et al., 1996), no instance of viral coinfection of such cells with JCV has been reported. Tat is known to be secreted from cells in which it is made. Here we ask whether such exogenous Tat can influence JCV replication in oligodendrocytes. We find that glial cells infected with either HIV-1 or JCV are in proximity at the outer edge of PML lesions. Exogenous Tat is avidly incorporated into cultured KG-1 oligodendroglioma cells over a 72-h period and is colocalized with endogenous Puralpha both nuclear and juxtanuclear. At concentrations in the medium well below the pM range, Tat stimulates several-fold the replication in vivo of DNA initiated at the JCV origin. These results define a pathway by which a protein made by HIV-1 can directly affect the course of infection by another disease-causing virus.
Daniel
Dianne C
DC
Department of Pathology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Kinoshita
Yayoi
Y
Khan
M Aamir
MA
Del Valle
Luis
L
Khalili
Kamel
K
Rappaport
Jay
J
Johnson
Edward M
EM
D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000276:immunology / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins; D015696:Gene Products, tat / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000502:physiology*; D008856:Microscopy, Fluorescence; D009837:Oligodendroglioma / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors; D014779:Virus Replication
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D015696:Gene Products, tat; C501130:PURA protein, human; D014157:Transcription Factors