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[Molecular-pathology analysis of regulatory region and transformation in JC virus]
1Second Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Abstract:
JC virus, an agent that causes a human demyelinating disease, progressive multifocal leukoencephalopathy (PML), is known to induce brain tumors in hamsters. The regulatory region of the virus reported to be implicated in its tissue specificity and to be highly variable among different isolates. In a study of the regulatory region, first we isolated the JC virus genome directly from the brain of a patient with suspected PML. We amplified the regulatory region of the virus by using the polymerase chain reaction, and we compared with three JC viruses which had been isolated previously (MAD-1, MAD-2, and TKY-1). The brain tissue was shown to be infected with JC virus, as confirmed by the presence of viral antigen on immunohistochemical testing and by the demonstration of viral nucleic acids upon in situ hybridization. Southern blot analysis of the regulatory region disclosed that the isolate from our patient, which was designated as NYS-1, was roughly homologous in all three types of JC viruses, with preservation of the constant regions. However, the cut site for PvuII in NYS-1 was different from that in MAD-1 and MAD-2, and a pair of cut sites, for Nco I-PvuII, was unique to TKY-1 and absent in NYS-1; this showed that NYS-1 was a new type of JC virus. Second, we compared the regulatory regions of TKY-1 and its viral DNA integrated in a hamster brain tumor cell line (I-23) induced by TKY-1. We found no great difference between these two genomes.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Researchers identified a new type of JC virus, NYS-1, from a patient with progressive multifocal leukoencephalopathy (PML). This discovery advances understanding of JC virus diversity and its role in neurological diseases.
Area of Science:
- Virology
- Neuroscience
- Oncology
Context:
- JC virus (JCV) is a human polyomavirus linked to progressive multifocal leukoencephalopathy (PML), a demyelinating disease.
- JCV is known to induce brain tumors in hamsters, suggesting oncogenic potential.
- The regulatory region of JCV is crucial for tissue specificity and exhibits significant variability among isolates.
Purpose:
- To characterize the regulatory region of a novel JC virus isolate (NYS-1) from a PML patient.
- To compare the NYS-1 regulatory region with previously identified JCV strains (MAD-1, MAD-2, TKY-1).
- To analyze the regulatory region of TKY-1 and its counterpart in a hamster brain tumor cell line (I-23).
Summary:
- A new JC virus type, NYS-1, was isolated from PML patient brain tissue, confirmed by viral antigen and nucleic acid detection.
- Southern blot analysis revealed NYS-1 shares homology with other JCV strains but possesses unique PvuII and Nco I-PvuII restriction sites, distinguishing it as a novel type.
- Comparison of TKY-1 and its integrated form in the I-23 cell line showed minimal genomic differences in their regulatory regions.
Impact:
- Identifies a new JC virus strain, expanding the known genetic diversity of JCV.
- Provides insights into the molecular variations within JCV regulatory regions, potentially influencing pathogenicity and tissue tropism.
- Contributes to understanding the mechanisms of JCV-induced diseases, including PML and oncogenesis.