Molecular Biology of Polyomavirus-Cell Interactions
Our laboratory studies the molecular biology of the small DNA tumor virus, BK polyomavirus. BKPyV is a ubiquitous human pathogen that establishes a subclinical, persistent infection of the urinary tract during early childhood. In healthy individuals, the virus is excreted periodically into the urine but does not cause disease, but in renal and bone marrow transplant patients, the virus can cause severe and sometimes life threatening illnesses. We are interested in the interplay between viral and host factors that determine whether the virus will persist or replicate in the cell. On the host cell side, our current efforts are focused on nuclear factors with which the virus interacts during infection. The first of these are called promyelocytic leukemia nuclear bodies (PML-NBs), which have been reported to play various roles in the biology of the cell. In the context of BKPyV infection, PML-NBs seems to be mainly anti-viral, although some of our data indicate that they facilitate early steps in the viral life cycle. The second is the DNA damage response, which the cell normally uses to detect and repair damaged DNA. Our evidence indicates that BKPyV both induces and requires a DNA damage response for its replication. We are currently investigating why the virus interacts with the damage response machinery. On the virus side, we are uncovering the genetic determinants on the viral chromosome that regulate the switch between persistence and active replication. Since there are no effective antiviral drugs with which to treat transplant patients, we are hopeful that these studies will lead to the identification of new therapeutic targets.
Abend, J.A., Low, J.A., and Imperiale, M.J. (2010). Global effects of BKV infection on gene expression in human primary kidney epithelial cells. Virology 397:73-79.
Swimm, A.I., Bornmann, W, Jiang, M., Imperiale, M.J., Lukacher, A.E., and Kalman, D. (2010). Abl-family tyrosine kinases regulate sialylated ganglioside receptors for polyomavirus. J. Virol. 84:4243-4251.
Casadevall, A. and Imperiale, M.J. (2010). Destruction of microbial collections in response to select agent and toxin list regulations. Biosecur. Bioterror. 8:151-154.
Broekema, N.M., Abend, J.R., Bennett, S.M., Butel, J.S., Vanchiere, J.A., and Imperiale, M.J. (2010). A system for the analysis of BKV non-coding control regions: application to clinical isolates from an HIV/AIDS patient. Virology 407:368â€“373.
Jiang, M., Entezami, P., Gamez, M., Stamminger, T., and Imperiale, M.J. (2011). Functional reorganization of promyelocytic leukemia nuclear bodies during BK virus infection. mBio 2(1):e00281-10. doi:10.1128/mBio.00281-10.
Imperiale, M.J. and Enquist, L.W. (2011). What's in a name? J. Virol. 85:5245.
Norkin, L.C., Johne, R., Buck, C. Allander, T., Atwood, W., Garcea, R., Imperiale, M., Major, E., and Ramqvist, T. (2011). Taxonomical developments in the family Polyomaviridae. Arch. Virol. 156:1627-1634.
Imperiale, M.J. and Casadevall, A. (2011). Bioterrorism: Lessons learned since the anthrax mailings. mBio, mBio 2(6):e00232-11. doi:10.1128/mBio.00232-11.
Broekema, N.M. and Imperiale, M.J. (2012). Efficient propagation of archetype BK and JC polyomaviruses. Virology 422:235-241.
Berns, K.I., Casadevall, A., Cohen, M.L., Ehrlich, S.A., Enquist, L.W., Fitch, J.P., Franz, D.R., Fraser-Liggett, C.M., Grant, C.M., Imperiale, M.J., Kanabrocki, J., Keim, P.S., Lemon, S.M., Levy, S.B., Lumpkin, J.R., Miller, J.F., Murch, R., Nance, M.E., Osterholm, M.T., Relman, D.A., Roth, J.A., and Vidaver, A.K. (2012). Policy: adaptations of avian flu virus are a cause for concern. Nature 482:153-154; Science 335:660-661.
Jiang, M. and Imperiale, M.J. (2012). Design stars: how small DNA viruses remodel the host nucleus, Future Virol., in press.
Imperiale, M.J. and Hanna, M.G. III. (2012). Biosafety considerations of mammalian-transmissible H5N1 influenza. mBio 3(2):e00043-12. doi:10.1128/mBio.00043-12.
Bennett, S.M., Broekema, N.B., and Imperiale, M.J. (2012). BK polyomavirus: emerging pathogen. Microbes Infect., in press.
Imperiale, M.J. (2012). Dual-use research after the avian influenza controversy. B. Atom. Sci. http://thebulletin.org/web-edition/op-eds/dual-use-research-after-the-avian-influenza-controversy.
Jiang, M., Zhao, L., Gamez, M., and Imperiale, M.J. (2012). Roles of ATM and ATR-mediated DNA damage responses during lytic BK polyomavirus infection. PLoS Pathog. 8(8): e1002898. doi:10.1371/journal.ppat.1002898.
Christensen, J.B., Ewing, S.G., and Imperiale, M.J. (2012). Identification and characterization of a DNA binding domain on the adenovirus IVa2 protein. Virology 433:124–130.
Broekema, N.M. and Imperiale, M.J. (2013). miRNA regulation of BK polyomavirus replication during early infection. Proc. Natl. Acad. Sci. USA 110:8200-8205.
Bennett, S.M., Jiang, M., and Imperiale, M.J. (2013). Role of cell type-specific ER-associated degradation in polyomavirus trafficking. J. Virol. 87:8843-8852.