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Journal of Virology, February 2001, p. 1996-2001, Vol. 75, No. 4
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.4.1996-2001.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mad-1 Is the Exclusive JC Virus Strain Present in the Human Colon, and Its Transcriptional Control Region Has a Deleted 98-Base-Pair Sequence in Colon Cancer Tissues

Luigi Ricciardiello, Dong K. Chang, Luigi Laghi, Ajay Goel, Christina L. Chang, and C. Richard Boland*

Department of Medicine and Cancer Center, University of California, San Diego, La Jolla, California 92093-0688

Received 28 August 2000/Accepted 6 November 2000

JC virus (JCV), along with other members of the polyomavirus family, encodes a class of highly conserved proteins, T antigens, that are capable of inducing aneuploidy in cultured cells. We have previously isolated T-antigen DNA variants of JCV from both colon cancer tissues and the corresponding nonneoplastic gastrointestinal tissues, raising new questions about the role of JCV in the development of chromosomal instability of the colon. Based on the sequence of the transcriptional control region (TCR), JCV can be classified as archetype or tandem repeat variants. Among the latter, Mad-1, the prototype virus first isolated from a patient with progressive multifocal leukoencephalopathy, is characterized by lacking the 23- and 66-bp sequences that are present in the archetype and by duplication of a 98-bp sequence. In this study, we evaluated differences in the TCR of JCV isolated from colon cancer tissues and nonneoplastic epithelium. To characterize JCV variants, we first treated eight pairs of DNA samples from colon cancers and noncancerous tissue with topoisomerase I and then amplified and cloned the JCV TCR. We obtained 285 recombinant clones from the JCV TCR, 157 from nonneoplastic samples, and 128 from colon cancer tissues. Of these clones, 262 spanned the length of the JCV Mad-1 TCR: 99.3% from nonneoplastic samples and 82.8% from colon cancer tissues. In sequencing 54 clones in both directions, we did not find archetype JCV either in the nonneoplastic tissue or in the cancer samples. From all colon cancer tissues, 18 clones had a deletion of one 98-bp tandem repeat. This deleted strain was not detected in any of the nonneoplastic tissues (14 versus 0% [chi 2 = 23.6; P < 0.001]). Our study demonstrates that the only JCV strain present in the human colon is Mad-1, and the variant with a single 98-bp sequence is found exclusively in the cancer tissues. This strain may be involved in the development of chromosomal instability.

* Corresponding author. Mailing address: Department of Medicine and Cancer, University of California, San Diego, 4028 Basic Science Building, 9500 Gilman Dr., La Jolla, CA 92093-0688. Phone: (858) 822-0300. Fax: (858) 822-0301. E-mail: crboland{at}ucsd.edu.

Journal of Virology, February 2001, p. 1996-2001, Vol. 75, No. 4
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.4.1996-2001.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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