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Cell type-specific expression of JC virus T antigen in primary and established cell lines from transgenic mice
A H Beggs1, J H Miner, G A Scangos
1Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218.
Abstract:
The highly restricted host range of JC virus (JCV) has made it difficult to study the biology of this common human papovavirus. To increase our understanding of the tissue specificity of this virus, we have examined the expression of the T antigen (T-Ag) in primary and established cell lines from various tissues of transgenic mice containing the JCV early region. In contrast to earlier results from a simian virus 40-containing transgenic mouse, there was no T-Ag expression in mesenchymal fibroblasts derived from two lines of JCV-transgenic mice. Instead, we isolated T-Ag-positive (T-Ag+) cells that had characteristics consistent with a neural crest origin. Furthermore, primary brain cultures contained many T-Ag+ astrocytes, but no expression was detected in macrophages, epithelial cells, neuronal cells nor, surprisingly, in oligodendrocytes. Continued passage of these cultures resulted in vigorously growing glial fibrillary acidic protein-positive, T-Ag+ astrocytes. Thus, the strict tissue specificity of JCV expression was maintained, despite the fact that the viral genome pre-existed in every tissue of these transgenic mice and these constraints on expression were preserved even when cells were explanted in vitro.
Insights
JC virus (JCV) T-antigen expression is restricted to neural crest-derived cells, specifically astrocytes, in transgenic mice. This tissue specificity is maintained even in vitro, offering insights into JCV biology.
Area of Science:
- Virology
- Molecular Biology
- Neuroscience
Background:
- JC virus (JCV), a common human papovavirus, exhibits a highly restricted host range, complicating biological studies.
- Understanding JCV's tissue specificity is crucial for elucidating its pathogenesis and host interactions.
Purpose of the Study:
- To investigate the tissue-specific expression of the JC virus T-antigen (T-Ag) in transgenic mice.
- To explore the cellular origins and characteristics of T-Ag expressing cells.
Main Methods:
- Generation and analysis of transgenic mice containing the JCV early region.
- Examination of T-Ag expression in primary and established cell lines from various tissues.
- Cellular characterization using markers for neural crest, astrocytes, macrophages, epithelial, neuronal, and oligodendrocytes.
Main Results:
- T-Ag expression was absent in mesenchymal fibroblasts but detected in cells of neural crest origin.
- Primary brain cultures showed T-Ag expression predominantly in astrocytes, with no expression in macrophages, epithelial cells, neurons, or oligodendrocytes.
- T-Ag-positive astrocytes maintained glial fibrillary acidic protein expression and proliferated in vitro, preserving JCV's tissue specificity.
Conclusions:
- JC virus T-Ag expression demonstrates strict tissue specificity, primarily occurring in cells of neural crest origin, particularly astrocytes.
- These findings highlight intrinsic cellular constraints governing JCV replication and pathogenesis, even when the viral genome is present ubiquitously.
- The study provides a valuable model for investigating JCV biology and its cell-type-specific interactions.