This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mendez, E. Articles by Jacobson, S. Search for Related Content PubMed PubMed Citation Articles by Mendez, E. Articles by Jacobson, S.

 Previous Article  |  Next Article 

J. Virol., Dec 1997, 9143-9149, Vol 71, No. 12
Copyright © 1997, American Society for Microbiology

Astrocyte-specific expression of human T-cell lymphotropic virus type 1 (HTLV-1) Tax: induction of tumor necrosis factor alpha and susceptibility to lysis by CD8+ HTLV-1-specific cytotoxic T cells

E Mendez, T Kawanishi, K Clemens, H Siomi, SS Soldan, P Calabresi, J Brady and S Jacobson
Neuroimmunology Branch, National Institute of Neurologic Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.

Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with a chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraperesis (HAM/TSP). Although the pathogenesis of this disease remains to be elucidated, the evidence suggests that immunopathological mechanisms are involved. Since HTLV-1 tax mRNA was colocalized with glial acidic fibrillary protein, a marker for astrocytes, we developed an in vitro model to assess whether HTLV-1 infection activates astrocytes to secrete cytokines or present viral immunodominant epitopes to virus-specific T cells. Two human astrocytic glioma cell lines, U251 and U373, were transfected with the 3' portion of the HTLV-1 genome and with the HTLV-1 tax gene under astrocyte- specific promoter control. In this study, we report that Tax-expressing astrocytic glioma transfectants activate the expression of tumor necrosis factor alpha mRNA in vitro. Furthermore, these Tax-expressing glioma transfectants can serve as immunological targets for HTLV-1- specific cytotoxic T lymphocytes (CTL). We propose that these events could contribute to the neuropathology of HAM/TSP, since infected astrocytes can become a source for inflammatory cytokines upon HTLV-1 infection and serve as targets for HTLV-1-specific CTL, resulting in parenchymal damage by direct lysis and/or cytokine release.

This article has been cited by other articles:

• Banerjee, P., Rochford, R., Antel, J., Canute, G., Wrzesinski, S., Sieburg, M., Feuer, G. (2007). Proinflammatory Cytokine Gene Induction by Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Tax in Primary Human Glial Cells. J. Virol. 81: 1690-1700 [Abstract] [Full Text]  
• Mogensen, T. H., Paludan, S. R. (2001). Molecular Pathways in Virus-Induced Cytokine Production. Microbiol. Mol. Biol. Rev. 65: 131-150 [Abstract] [Full Text]  
• Szymocha, R., Akaoka, H., Dutuit, M., Malcus, C., Didier-Bazes, M., Belin, M.-F., Giraudon, P. (2000). Human T-Cell Lymphotropic Virus Type 1-Infected T Lymphocytes Impair Catabolism and Uptake of Glutamate by Astrocytes via Tax-1 and Tumor Necrosis Factor Alpha. J. Virol. 74: 6433-6441 [Abstract] [Full Text]  
• Walz, R., Portela, L. V. C., Tort, A. B. L., Neto, E. C., Fernandes, L. N. T., Goncalves, C. A., Souza, D. O. (2000). Serum S100B levels in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. Neurology 54: 2021-2022 [Full Text]