Faculty

 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 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 replication when the immune system is suppressed. In addition, BKV is a known oncogenic virus in rodents, and viral sequences have recently been identified in human tumors, making it a potential co-factor in cancer. We have been examining prostate tumors for the presence and expression of the BKV genome, and find that the viral oncoprotein, large T antigen, is expressed in early stages of prostate cancer.

   Another project involves assembly 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 52/55K 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 Kochanek, S. (2004). Adenovirus vectors: biology, design, and production. In: W. Doerfler and P. Böhm (eds.): Adenoviruses: Model and Vectors in Virus-Host Interactions (Springer, Berlin), Curr. Topics Microbiol. Immunol. 273:335-357.

Noordmans, A.J., Song, D.K., Noordmans, C.J., Garrity-Moses, M., During, M.J., Fitzsimons, H.L., Imperiale, M.J., and Boulis, N.M. (2004). Adeno-associated viral glutamate decarboxylase expression in the lateral nucleus of the rat hypothalamus reduces feeding behavior. Gene Ther. 11:797-804.

Low, J., Humes, H.D., Szczypka, M., and Imperiale, M.J. (2004). BKV and SV40 infection of human kidney tubular epithelial cells in vitro. Virology 323:182-188.

Das, D., Shah, R.B., and Imperiale, M.J. (2004). Detection and expression of human BK virus sequences in neoplastic prostate tissues. Oncogene 23:7031-7046.

McConnell, M.J. and Imperiale, M.J. (2004). Biology of adenovirus and its use as a vector for gene therapy. Hum. Gene Ther. 15:1022-1033.

Perez-Romero, P., Tyler, R.E., Abend, J.R., Dus, M., and Imperiale, M.J. (2005). Analysis of the interaction of the adenovirus L1 52/55 kDa and IVa2 proteins with the packaging sequence in vivo and in vitro. J. Virol. 79:2366-2374.

Liu, J.K., Teng, Q., Garrity-Moses, M., Federici, T., Tanase, D., Imperiale, M.J., and Boulis, N.M. (2005). A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting. Neurobiol. Dis. 19:407-418.

McCabe. M.T., Low, J.A., Daignault, S., Imperiale, M.J., Wojno, K.J., and Day, M.L. (2006). Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer. Cancer Res. 66:385-392.

McConnell, M.J., Hanna, P.C., and Imperiale, M.J. (2006). Cytokine response and survival in mice immunized with an adenovirus expressing B. anthracis protective antigen domain 4. Infect. Immun. 74:1009-1015.

Low, J.A., Magnuson, B., Tsai, B., and Imperiale, M.J. (2006). Identification of gangliosides GD1b and GT1b as receptors for BK virus. J. Virol. 80:1361-1366.

Perez-Romero, P. Gustin, K.E., and Imperiale, M.J. (2006). Dependence of the encapsidation function of the adenovirus L1 52/55 kDa protein on its ability to bind the packaging sequence. J. Virol. 80:1965-1971.

McCabe. M.T., Low, J.A., Imperiale, M.J., and Day, M.L.(2006). Human polyomavirus BKV transcriptionally activates DNA methyltransferase 1 through the pRb/E2F pathway.  Oncogene, in press.

McConnell, M.J., Danthinne, X., and Imperiale, M.J. (2006). Characterization of a permissive epitope insertion site in adenovirus hexon. J. Virol. 80:5361-5370.

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.