Faculty
 |
Michael J. Imperiale |
Molecular Biology of Tumor Virus-Cell Interactions
Our laboratory studies the molecular biology of the small DNA tumor viruses. We are particularly interested in how these viruses assemble, how they deregulate normal cell growth control, and how they interact with the host immune system.
One major area of study is the interaction of the human polyomavirus, BKV, with the host cell. BKV is a DNA virus that establishes a subclinical, persistent infection of the urinary tract. In healthy individuals, the virus does not cause disease, but in renal and bone marrow transplant patients, the virus can reactivate and cause life threatening illness. We are interested in the interplay between viral and host factors that allow the virus to persist in the presence of a healthy immune system, as well as those that drive lytic replicatio when the immune system is suppressed. We have demonstrated that interferon-g can inhibit viral transcription in renal proximal tubular epithelial cells, the natural host cell for the virus. Our current efforts are aimed at determining the mechanism of inhibition, which may involve nuclear structures called PML nuclear bodies. These have been shown to be involved in the interferon response to other DNA viruses.
Another project involves assembly of adenovirus, a virus that is a major cause of upper respiratory and ocular infections in children, and that also can cause serious illness in the transplant setting. We have identified two viral proteins, the L1 52/55 kDa protein and the IVa2 protein, that are required for packaging of the viral genome into capsids. Moreover, it appears that the IVa2 protein is required for capsid assembly. We are currently attempting to elucidate the mechanism by which these two proteins function to allow the virus to encapsidate its DNA. These studies will enhance our knowledge of how the virus carries out this important step in its life cycle.
Selected Publications:
Imperiale, M.J. and Major, E.O. (2007). Polyomaviruses. In: D.M. Knipe, P.M. Howley, D.E. Griffin, R.A. Lamb, M.A. Martin, B. Roizman, and S.E. Straus (eds.): Fields Virology, 5th Edition, Lippincott Williams & Wilkins, Philadelphia.
McConnell, M.J., Hanna, P.C., and Imperiale, M.J. (2007). Adenovirus-based prime-boost immunization for rapid vaccination against anthrax. Mol. Ther. 15:203-210.
Abend, J.R., Low, J.A., and Imperiale, M.J. (2007). Inhibitory effect of gamma interferon on BK virus gene expression and replication. J. Virol. 81:272-279.
Tyler, R.E., Ewing, S. G., and Imperiale, M.J. (2007). Formation of a multiple protein complex on the adenovirus packaging sequence by the IVa2 protein. J. Virol. 81:3447-3454.
Imperiale, M.J. (2007). Gene therapy and biosecurity. Mol. Ther. 15:648-649.
Ewing, S.G., Byrd, S.A., Christensen, J.B., Tyler, R.E., and Imperiale, M.J. (2007) Ternary complex formation on the adenovirus packaging sequence by the IVa2 and L4 22 kDa proteins. J. Virol. 81:12450-12457.
Das, D., Wojno, K., and Imperiale, M.J. (2008). BKV as a cofactor in the etiology of prostate cancer in its early stages. J. Virol. 82:2705-2714.
Imperiale, M.J. (2008). Keeping adenovirus away from the liver. Cell Host Microbe 3:119-120.
Abend, J.R. and Imperiale, M.J. (2008). Transforming growth factor beta-mediated regulation of BK virus gene expression. Virology 378:6-12.
Christensen, J.B., Byrd, S.A., Walker, A.K., Strahler, J.R., Andrews, P.C., and Imperiale, M.J. (2008). Presence of the adenovirus IVa2 protein at a single vertex of the mature virion. J. Virol. 82:9086-9093.
Casadevall, A., Ehrlich, S.A., Franz, D.R., Imperiale, M.J., and Keim, P.S. (2008). Biodefense research: a win-win challenge. Biosecur. Bioterror. 6:291-292.
Das, D. and Imperiale, M.J. (2009). Transformation by polyomaviruses. In: B. Damania and J.M. Pipas (eds.): DNA Tumor Viruses, Springer, New York, pp. 25-52.
Jiang, M., Abend, J.R., Tsai, B., and Imperiale, M.J. (2009). Early events during BK virus entry and disassembly. J. Virol. 83:1350-1358.
Jiang, M., Abend, J.R., Johnson, S.F., and Imperiale, M.J. (2009). The role of polyomaviruses in human disease. Virology 384:266-273.
Mahon, C., Liang, B., Tikhanovich, I., Abend, J.R., Imperiale, M.J., Nasheuer. H.P., and Folk, W.R. (2009) Restriction of human polyomavirus BKV DNA replication in murine cells and extracts. J. Virol. 83:5708-5717.
Abend, J.R., Joseph, A.E., Das, D., Campbell-Cecen, D.B., and Imperiale, M.J. (2009). A truncated T antigen expressed from an alternatively spliced BK virus early mRNA. J. Gen. Virol. 90:1238-1245.
Editors of the Journal of Virology. (2009). Virology in the 21st century. J. Virol. 83:5296-5308.
Abend, J.R., Jiang, M., and Imperiale, M.J. (2009). BK virus and human cancer: Innocent until proven guilty. Sem. Cancer Biol. 19:252-260.
