Detection of JC polyomavirus DNA sequences and cellular localization of T-antigen and agnoprotein in oligodendrogliomas.
OBJECTIVE
Productive infection of the human neurotropic polyomavirus JCPyV in oligodendrocytes leads to the development of progressive multifocal leukoencephalopathy, a fatal demyelinating disorder of the central nervous system. In addition to its role in viral infection, JCPyV T-antigen can transform cells in vitro and induce tumors in experimental animals in the absence of viral DNA replication and late gene expression. The goal of this study is to examine the presence of JCPyV DNA sequences and viral antigens in a series of human oligodendrogliomas.


METHODS
A total of 20 well-characterized oligodendrogliomas were examined for detection of the JCPyV genome by PCR and immunohistochemistry for expression of viral proteins.


RESULTS
Gene amplification has revealed the presence of JCPyV DNA sequences corresponding to the NH2-terminal of T-antigen in 15 of 20 samples. DNA sequences corresponding to late regions, which are responsible for production of the capsid protein, VP1, were detected in 14 of 20 samples. Sequencing of the viral control region determined the presence of JCPyV Mad-4 or JCPyV(CY) in these tumors. By immunohistochemistry, T-antigen expression was detected in the nuclei of tumor cells from 10 samples that also contained corresponding DNA sequences by PCR. Eleven of 20 tumors exhibited immunoreactivity for the late auxiliary gene product, agnoprotein. None of the samples showed immunoreactivity for the capsid proteins, ruling out productive infection of neoplastic cells by JCPyV.


CONCLUSIONS
Collectively, these observations provide new evidence in support of the association of the oncogenic human neurotropic JCPyV and oligodendrogliomas.
Del Valle
Luis
L
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.
Enam
Sahnila
S
Lara
César
C
Ortiz-Hidalgo
Carlos
C
Katsetos
Christos D
CD
Khalili
Kamel
K
D000328:Adult; D000368:Aged; D000957:Antigens, Viral, Tumor / Q000096:biosynthesis*; D001483:Base Sequence; D015139:Blotting, Southern; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D036022:Capsid Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009837:Oligodendroglioma / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D010940:Plant Proteins; D016133:Polymerase Chain Reaction; D011120:Polyomavirus / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis*; D054334:Viral Regulatory and Accessory Proteins; D000086082:Viroporin Proteins
D000957:Antigens, Viral, Tumor; D036022:Capsid Proteins; D004268:DNA-Binding Proteins; D010940:Plant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins