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Journal of Virology, December 2001, p. 12339-12346, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12339-12346.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Small Tumor Virus Genomes Are Integrated near Nuclear Matrix Attachment Regions in Transformed Cells

Katherine A. Shera,1 Christopher A. Shera,2,3 and James K. McDougall1,*

Cancer Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-10241; Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 021142; and Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 021153

Received 5 July 2001/Accepted 21 September 2001

More than 15% of human cancers have a viral etiology. In benign lesions induced by the small DNA tumor viruses, viral genomes are typically maintained extrachromosomally. Malignant progression is often associated with viral integration into host cell chromatin. To study the role of viral integration in tumorigenesis, we analyzed the positions of integrated viral genomes in tumors and tumor cell lines induced by the small oncogenic viruses, including the high-risk human papillomaviruses, hepatitis B virus, simian virus 40, and human T-cell leukemia virus type 1. We show that viral integrations in tumor cells lie near cellular sequences identified as nuclear matrix attachment regions (MARs), while integrations in nonneoplastic cells show no significant correlation with these regions. In mammalian cells, the nuclear matrix functions in gene expression and DNA replication. MARs play varied but poorly understood roles in eukaryotic gene expression. Our results suggest that integrated tumor virus genomes are subject to MAR-mediated transcriptional regulation, providing insight into mechanisms of viral carcinogenesis. Furthermore, the viral oncoproteins serve as invaluable tools for the study of mechanisms controlling cellular growth. Similarly, our demonstration that integrated viral genomes may be subject to MAR-mediated transcriptional effects should facilitate elucidation of fundamental mechanisms regulating eukaryotic gene expression.

* Corresponding author. Mailing address: Cancer Biology Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-105, Seattle, WA 98109-1024. Phone: (206) 667-4498. Fax: (206) 667-5815. E-mail: jmcdouga{at}fhcrc.org.

Journal of Virology, December 2001, p. 12339-12346, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12339-12346.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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