| Name: |
| Elizabeth Ann (Lee) Fortunato |
| Title: |
| Associate Professor |
| Degree: |
| Ph.D., 1995, University of California, San Diego |
| Phone: |
| (208) 885-6966 |
| Fax: |
| (208) 885-6518 |
| Email: |
| lfort@uidaho.edu |
| Lab/Office Location: |
| Gibb Hall, Room 126 |
| Lab Phone: |
| (208) 885-9237 |
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| Research Interests: |
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The long-term goal of our work is to understand the mechanism behind the development of morbidity and mortality in infants
congenitally infected with human cytomegalovirus (HCMV). In the last 5 years we have shown that HCMV interacts with the key cell
cycle regulatory protein p53 and sequesters it from its normal cellular partners, thereby disabling its capacity to control cell
cycle arrest and apoptosis in the infected cell. This sequestration into the viral replication centers is not unique for p53, but
also occurs for several proteins of the DNA repair machinery. We have also recently shown that specific breaks are induced on
chromosome 1q in the permissive host cell when infection is initiated during S-phase. This damage does not require de novo viral
protein expression, which has tremendous implications for infection of semi- to non-permissive cell types like those in the
developing brain. Our results, when coupled with the existing literature, highlight the genotoxic effects of HCMV. Our objective is
to study the importance of both the timing of infection and the permissivity of the host cell on the interaction of HCMV with the
host cell's DNA and DNA repair machinery.
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Two main projects are progressing in the lab at this time. The first deals with the interaction of HCMV with the key cell cycle
regulatory protein p53. We are interested in the initial upregulation of the protein by viral infection. We wish to determine the
mechanism of stabilization of the protein and of its sequestration into the viral replication centers once they are formed. In
addition, we wish to determine the role (if any) of the p53 in maintaining the fidelity of viral replication and repair. The second
main project is studying the ability of virus-infected cells to repair insult to the cellular DNA (either virus or externally
imposed). Can a cell that is damaged specifically at the chromosome 1 sites repair that damage? If not, does the damage get passed
on to subsequent daughter populations? Also, once viral replication centers are set up within the virus-infected nucleus, is there a
preferential repair of viral over cellular DNA due to sequestration of the cellular components of the DNA repair machinery into the
viral replication centers?
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| Selected Publications: |
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Nystad M, Fagerheim T, Brox V, Fortunato E.A. and O. Nilssen. 2008. Human cytomegalovirus (HCMV) and hearing impairment: Infection of fibroblast cells with HCMV induces chromosome breaks at 1q23.3, between loci DFNA7 and DFNA49-Both involved in dominantly inherited, sensorineural, hearing impairment. Mut Res. 637: 56-65.
Luo MH and E.A. Fortunato. 2007. Long-term infection and virus shedding of human cytomegalovirus, in T98G glioblastoma cells. J Virol. 81: 10424-36
M. H. Luo, K. Rosenke, K. Czornak and E.A. Fortunato. 2007 Human cytomegalovirus disrupts both ATM and ATR-mediated DNA damage responses during lytic infection. J. Virol. 81:1934-50.
M. H. Luo, K. Rosenke, K. Czornak and E.A. Fortunato. 2007 Human cytomegalovirus disrupts both ATM and ATR-mediated DNA damage responses during lytic infection. J. Virol. 81:1934-50.
N. C. Casavant, M.H. Luo, K. Rosenke,T. Winegardner, A. Zurawska and E.A. Fortunato. 2006. Potential Role for p53 in the Permissive Life Cycle of Human Cytomegalovirus. J. Virol. 80:8390-401.
K. Rosenke, M. A. Samuel, E. T. McDowell, M. A. Toerne and E. A. Fortunato. 2006. An intact sequence-specific DNA binding domain is required for human cytomegalovirus-mediated sequestration of p53 and may promote in vivo binding to the viral genome during infection. Virology 348: 19-34.
Rosenke, K. and E.A. Fortunato. 2004. Bromodeoxyuridine-labeled viral particles as a tool for visualization of the immediate-early events of human cytomegalovirus infection. J Virol. 78: 7818-22.
Fortunato, E.A., V. Sanchez, J. Yen and D.H. Spector. 2002. Infection of cells with human cytomegalovirus during S phase results in a blockade to immediate-early gene expression that can be overcome by inhibition of the proteasome. J. Virol.76:5369-79
Fortunato, E.A., A.K. McElroy, V. Sanchez and D.H. Spector. 2000. Exploitation of cellular signaling and regulatory pathways by human cytomegalovirus. Trends in Microbio. 8: 111-19.
Fortunato, E. A., M. L. Dell'Aquila and D. H. Spector. 2000. Specific chromosome 1 breaks induced by human cytomegalovirus. Proc. Natl. Acad. Sci. USA 97: 853-58.
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