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  • Infectivity spectrum of MMTV
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• Research Documentation

Indik/Günzburg: Infectivity spectrum of MMTV

A large body of scientific evidence accumulated over several decades suggests that Mouse Mammary Tumour Virus (MMTV) or a very close relative is etiologically involved in sporadically occurring breast cancer.  Recently, several independent laboratories have detected sequences very closely related to MMTV in 30 to 40% human breast cancer samples but not in non-cancerous tissue. Our laboratory has also recently demonstrated that MMTV can not only productively infect a variety of human cell lines but also spreads rapidly in these cells. This evidence supports the hypothesis put forward by others that MMTV may be zoonotically transferred from mice to humans.

In a preliminary pilot study we have been able to detect both the presence of MMTV sequences, as well as its integration site in about 10% of Austrian human breast cancer patients. In the course of the proposed project we would like to extend the study in humans as well as analysing canine and feline mammary carcinomas. Further we intend to clone full length proviruses from the identified integration sites and demonstrate the infectivity of these cloned proviruses both in vitro as well as in vivo. Additionally, we plan to follow the reactivity of human, feline and canine mammary tumour patient sera with MMTV viral proteins. We have previously shown that human cells are permissive for infection with MMTV carrying Env protein derived from the GR (European) strain of MMTV. Using hybrid viruses based on our infectious EGFP-tagged molecular clone of MMTV we will also check whether the American strain of MMTV (C3H) is also able to infect other species.

Publication List

1. Saller, R.M., Öztürk-Winder, F., Salmons, B. and Günzburg, W.H. (1998) Construction and characterization of a hybrid mouse mammary tumor virus/murine leukemia virus based retroviral vector. J. Virol. 72, 1699-1703
2. Casper, C., Leib-Mösch, C., Salmons, B., Günzburg, W.H., Hoefler, H., Erfle, V. and Atkinson, M.J. (1998) Mapping of a mouse mammary tumor virus integration site by retroviral LTR-arbitrary primed polymerase chain reaction. Virus Res. 54, 207-215
3. Salmons, B., Miethke, T., Wintersperger, S., Müller, M., Brem, G. and Günzburg, W.H. (2000) Superantigen expression is driven by both MMTV LTR promoters in transgenic mice. J. Virol. 74, 2900-2902
4. Indik, S., Günzburg, W.H., Salmons, B. and Rouault, F. (2005) A novel, mouse mammary tumor virus encoded protein with Rev-like properties. Virology 337, 1-6
5. Indik, S., Günzburg, W.H., Salmons, B. and Rouault, F. (2005) Mouse mammary tumor virus productively infects human cells. Cancer Research 65, 6651-6659
6. Rungaldier, S., Badihi Nejad Asl, S., Günzburg, W.H., Salmons, B. and Rouault, F. (2005) Abundant authentic MMTV-Env production from a provirus lacking the major LTR promoter. Virology 342, 201-214
7. Metzner, C., Salmons, B., Günzburg, W.H., Gemeiner, M., Miller, I., Gesslbauer, B., Kungl, A. and Dangerfield, J.A. (2006) MMTV accessory factor Naf affects cellular gene expression. Virology 346, 139-150.
8. Günzburg, W.H., Hlavaty, J., Indik, S., Tabotta, W., Walter, I., Hohenadl, C., Brandtner, E.M., Rouault, F., Renner, M. and Salmons, B. (2006) New generations of retroviral vector for safe, efficient and targeted gene therapy. Gene Therapy and Molecular Biology 10, 185-192
9. Rouault, F., Badihi Nejad Asl, S., Rungaldier, S., Fuchs, E., Salmons, B. and Günzburg, W.H. (2007) Promoter complex in the central region of the MMTV. Journal of Virology 81, 12572-12581
10. Indik, S., Günzburg, W.H., Kulich, P., Salmons, B. and Rouault, F. (2007) Rapid spread of mouse mammary tumor virus in cultured human breast cells. Retrovirology 4, 73
11. Faschinger, A., Rouault, F. Sollner, J., Lukas, A., Salmons, B., Günzburg, W.H. and Indik, S. (2008) Mouse mammary tumor virus integration site selection in human and mouse genomes. Journal of Virology 82, 1360-1367
12. Klein, R., Ruttkowski, B., Schwab, S., Peterbauer, T. Salmons, B., Günzburg, W.H.  and Hohenadl, C. (2008) Mouse mammary tumor virus (MMTV) promoter-containing retroviral promoter conversion (ProCon) vectors for gene-directed enzyme prodrug therapy are functional in vitro and in vivo. Journal of Biomedicine and Biotechnology, 2008:683505
13. Müllner, M., Günzburg, W.H., Salmons, B. and Indik, S. (2008) Identification of the Rem responsive element of mouse mammary tumor virus. Nucleic Acids Research 36, 6284-6294