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JC virus T′135, T′136 and T′165 proteins interact with cellular p107 and p130 in vivo and influence viral transformation potential

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Abstract

The JC virus (JCV) regulatory proteins, large T antigen, small t antigen, T′135, T′136, and T′165, are encoded by five transcripts alternatively spliced from the viral early precursor mRNA. T antigen and the T′ proteins share N-terminal amino acid sequences that include the L × C × E and J domains, motifs in SV40 T antigen known to mediate binding to the retinoblastoma (Rb) proteins and Hsc70, respectively. In this study, G418-resistant cell lines were created that express wild-type or mutant JCV T antigen and T′ proteins individually or in combination. These cell lines were used to evaluate the ability of each viral protein to bind p107 and p130 in vivo, and to influence cellular growth characteristics. Differences were observed in the abilities of individual T′ proteins to bind p107 and p130 and to alter their phosphorylation status. The T′ proteins were also found to localize to the cell’s nucleus and to be phosphorylated in a cell cycle-dependent manner. JCV T antigen and T′ proteins expressed from a cytomegalovirus promoter failed to induce dense focus formation in Rat2 cells, but they did cooperate with a mutant Ras protein to overcome cellular senescence and immortalize rat embryo fibroblasts. These data indicate that, despite their sequence similarities, JCV early proteins exhibit unique activities that, in combination, effect the inactivation of cell cycle regulators, a requirement for polyomavirus-induced transformation.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA

    Brigitte Bollag, Lisa H. Kilpatrick, Shiva K. Tyagarajan & Richard J. Frisque

  2. Department of Microbiology and Immunology, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA

    Mary J. Tevethia

Authors
  1. Brigitte Bollag
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  2. Lisa H. Kilpatrick
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  3. Shiva K. Tyagarajan
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  4. Mary J. Tevethia
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  5. Richard J. Frisque
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Correspondence to Richard J. Frisque.

Additional information

This work was supported by U.S. Public Health Service grants from the National Institute of Neurological Disorders and Stroke (S11 NS41833) and the National Cancer Institute (CA-115771 to RJF; CA-24694 to MJT), and by a grant from the Pennsylvania Department of Health using Tobacco Settlement Funds. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions.

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Bollag, B., Kilpatrick, L.H., Tyagarajan, S.K. et al. JC virus T′135, T′136 and T′165 proteins interact with cellular p107 and p130 in vivo and influence viral transformation potential. Journal of NeuroVirology 12, 428–442 (2006). https://doi.org/10.1080/13550280601009553

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  • DOI: https://doi.org/10.1080/13550280601009553

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