Abstract
The state and expression of the hamster polyomavirus genome in a large panel of virus-induced lymphomas have been investigated. The viral genome is present within tumor cells either as abundant nonrandomly deleted extrachromosomal copies or as a single copy integrated into cellular DNA. We show that these two physical states are likely to be functionally equivalent: first, deletion and integration of the viral genome both inactivate the late coding region; second, the amount of viral early RNAs yielded by a single integrated copy appears to be very similar to that associated with several thousands of extrachromosomal copies of the viral genome. These data underline two essential requisites for hamster polyomavirus to become lymphomagenous: suppression of the late coding functions of the viral genome and expression of the viral oncogenes above a threshold level.
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- Bastien C., Feunteun J. The hamster polyomavirus transforming properties. Oncogene. 1988 Feb;2(2):129–135. [PubMed] [Google Scholar]
- Berebbi M., Dandolo L., Hassoun J., Bernard A. M., Blangy D. Specific tissue targeting of polyoma virus oncogenicity in athymic nude mice. Oncogene. 1988 Feb;2(2):149–156. [PubMed] [Google Scholar]
- Bikel I., Montano X., Agha M. E., Brown M., McCormack M., Boltax J., Livingston D. M. SV40 small t antigen enhances the transformation activity of limiting concentrations of SV40 large T antigen. Cell. 1987 Jan 30;48(2):321–330. doi: 10.1016/0092-8674(87)90435-1. [DOI] [PubMed] [Google Scholar]
- Braun L., Mikumo R., Mark H. F., Lauchlan S. Analysis of the growth properties and physical state of the human papillomavirus type 16 genome in cell lines derived from primary cervical tumors. Am J Pathol. 1993 Sep;143(3):832–844. [PMC free article] [PubMed] [Google Scholar]
- Bullock P., Champoux J. J., Botchan M. Association of crossover points with topoisomerase I cleavage sites: a model for nonhomologous recombination. Science. 1985 Nov 22;230(4728):954–958. doi: 10.1126/science.2997924. [DOI] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Choo K. B., Cheung W. F., Liew L. N., Lee H. H., Han S. H. Presence of catenated human papillomavirus type 16 episomes in a cervical carcinoma cell line. J Virol. 1989 Feb;63(2):782–789. doi: 10.1128/jvi.63.2.782-789.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cullen A. P., Reid R., Campion M., Lörincz A. T. Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. J Virol. 1991 Feb;65(2):606–612. doi: 10.1128/jvi.65.2.606-612.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delmas V., Bastien C., Scherneck S., Feunteun J. A new member of the polyomavirus family: the hamster papovavirus. Complete nucleotide sequence and transformation properties. EMBO J. 1985 May;4(5):1279–1286. doi: 10.1002/j.1460-2075.1985.tb03773.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delmas V., de La Roche Saint André C., Gardes M., Goutebroze L., Feunteun J. Early gene expression in lymphoma-associated hamster polyomavirus viral genomes. Oncogene. 1992 Feb;7(2):295–302. [PubMed] [Google Scholar]
- Graffi A., Bender E., Schramm T., Graffi I., Bierwolf D. Studies on the hamster papilloma and the hamster virus lymphoma. Bibl Haematol. 1970;(36):293–303. doi: 10.1159/000391720. [DOI] [PubMed] [Google Scholar]
- Matsukura T., Koi S., Sugase M. Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers. Virology. 1989 Sep;172(1):63–72. doi: 10.1016/0042-6822(89)90107-4. [DOI] [PubMed] [Google Scholar]
- Mazur S., Goodhardt M., Feunteun J., de La Roche Saint André C. In vivo replication of the hamster polyomavirus genome and generation of specific deletions in the process of lymphomagenesis. J Virol. 1994 Sep;68(9):5629–5637. doi: 10.1128/jvi.68.9.5629-5637.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rösl F., Westphal E. M., zur Hausen H. Chromatin structure and transcriptional regulation of human papillomavirus type 18 DNA in HeLa cells. Mol Carcinog. 1989;2(2):72–80. doi: 10.1002/mc.2940020205. [DOI] [PubMed] [Google Scholar]
- Scherneck S., Delmas V., Vogel F., Feunteun J. Induction of lymphomas by the hamster papovavirus correlates with massive replication of nonrandomly deleted extrachromosomal viral genomes. J Virol. 1987 Dec;61(12):3992–3998. doi: 10.1128/jvi.61.12.3992-3998.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwab M. E., Thoenen H. Selective binding, uptake, and retrograde transport of tetanus toxin by nerve terminals in the rat iris. An electron microscope study using colloidal gold as a tracer. J Cell Biol. 1978 Apr;77(1):1–13. doi: 10.1083/jcb.77.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sellins K. S., Cohen J. J. Polyomavirus DNA is damaged in target cells during cytotoxic T-lymphocyte-mediated killing. J Virol. 1989 Feb;63(2):572–578. doi: 10.1128/jvi.63.2.572-578.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spence R. P., Murray A., Banks L., Kelland L. R., Crawford L. Analysis of human papillomavirus sequences in cell lines recently derived from cervical cancers. Cancer Res. 1988 Jan 15;48(2):324–328. [PubMed] [Google Scholar]
- Talmage D. A., Freund R., Dubensky T., Salcedo M., Gariglio P., Rangel L. M., Dawe C. J., Benjamin T. L. Heterogeneity in state and expression of viral DNA in polyoma virus-induced tumors of the mouse. Virology. 1992 Apr;187(2):734–747. doi: 10.1016/0042-6822(92)90476-6. [DOI] [PubMed] [Google Scholar]
- Yee C., Krishnan-Hewlett I., Baker C. C., Schlegel R., Howley P. M. Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. Am J Pathol. 1985 Jun;119(3):361–366. [PMC free article] [PubMed] [Google Scholar]
- de La Roche Saint André C., Mazur S., Feunteun J. Viral genomes maintained extrachromosomally in hamster polyomavirus-induced lymphomas display a cell-specific replication in vitro. J Virol. 1993 Dec;67(12):7172–7180. doi: 10.1128/jvi.67.12.7172-7180.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de la Roche Saint André C., Harper F., Feunteun J. Analysis of the hamster polyomavirus infection in vitro: host-restricted productive cycle. Virology. 1990 Aug;177(2):532–540. doi: 10.1016/0042-6822(90)90518-v. [DOI] [PubMed] [Google Scholar]
- zur Hausen H. Human papillomaviruses in the pathogenesis of anogenital cancer. Virology. 1991 Sep;184(1):9–13. doi: 10.1016/0042-6822(91)90816-t. [DOI] [PubMed] [Google Scholar]
- zur Hausen H. Viruses in human cancers. Science. 1991 Nov 22;254(5035):1167–1173. doi: 10.1126/science.1659743. [DOI] [PubMed] [Google Scholar]