Journal article
Astrocytes as potential source of cell-free Tax during human T cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis
Journal of neurovirology, Vol.13, pp.91-91
01 Jan 2007
Abstract
The mechanism of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis is heavily reliant on the viral transcriptional transactivator protein Tax. The presence of cell-free Tax has been demonstrated in the cerebrospinal fluid of HAM/TSP and the effects of extracellular Tax has been reported in a number of cell types including microglia and neurons. Since astrocytes are the primary glial cells within the brain and are known to be infected with HTLV-1, we hypothesized that HTLV-1-infected astrocytes could play a critical role in HAM/TSP pathogenesis by releasing Tax. In the study reported herein, astrocytes were transduced with lentivirus vector expressing green fluorescent protein labeled Tax (Tax-GFP), and were observed under fluorescent microscopy to determine localization of the protein. Tax was found to be present in high concentrations within cytoplasm, with very little or no Tax being found in the nucleus, 48-hr post-transduction. Subsequently, both cell lysate and supernatant were collected from the transduced cells and analyzed for the presence of Tax via western immunoblot analysis. Results indicated that Tax is released by astrocytes within 48 hr of transduction, in accordance with visual confirmation of Tax presence in the cytoplasm. A cytokine array analyses was also performed to monitor the changes in selected cytokine levels within astrocytes in response to Tax. The Tax-mediated induction of proinflammatory cytokines and chemokines was observed indicating activation of astrocytes and alteration in their function. Future experimentation will determine the effect of Tax-transduced astrocytes on neuronal damage to correlate these observations with HAM/TSP pathogenesis.
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Details
- Title
- Astrocytes as potential source of cell-free Tax during human T cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis
- Creators
- Z KhanP JainV LepoutreK QuannB Wigdahl
- Publication Details
- Journal of neurovirology, Vol.13, pp.91-91
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170340004721