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Regulation of the host range of human papovavirus JCV
Abstract:
Human papovavirus JCV is associated with the human demyelinating disorder progressive multifocal leukoencephalopathy. In tissue culture, the virus is largely restricted to growth in primary human fetal glial cell. In this study, we demonstrate two levels of regulation of the viral host range. Expression of the early JCV mRNA, which encodes the essential viral protein, large tumor antigen (T antigen), depends on recognition of the early enhancer/promoter elements by tissue-specific factors found in both human and rodent glial cells. In the presence of JCV T antigen, viral DNA replication requires a species-specific factor, presumably a component of DNA polymerase, which is found in a wide range of primate cells. We further demonstrate that simian virus 40 T antigen has sufficient homology to efficiently substitute for the analogous JCV protein in initiating viral DNA replication.
Insights
Human papovavirus JCV causes progressive multifocal leukoencephalopathy. Its host range is regulated by glial cell factors for early gene expression and primate-specific factors for DNA replication.
Area of Science:
- Virology
- Neuroscience
- Molecular Biology
Background:
- Human papovavirus JCV is linked to progressive multifocal leukoencephalopathy (PML), a human demyelinating disease.
- JCV replication in cell culture is primarily restricted to human fetal glial cells.
Purpose of the Study:
- To investigate the regulatory mechanisms governing the host range of human papovavirus JCV.
- To identify factors essential for JCV gene expression and DNA replication.
Main Methods:
- Analysis of JCV early mRNA expression in glial cells.
- Investigation of JCV DNA replication in the presence of JCV T antigen.
- Comparative studies using simian virus 40 T antigen.
Main Results:
- JCV early gene expression is regulated by tissue-specific factors in glial cells (human and rodent).
- Viral DNA replication necessitates a species-specific factor present in primate cells.
- Simian virus 40 T antigen can substitute for JCV T antigen in initiating viral DNA replication.
Conclusions:
- JCV host range is controlled by distinct regulatory mechanisms at the levels of gene expression and DNA replication.
- These findings provide insights into the molecular basis of JCV pathogenesis and host-virus interactions.