Oral ulcerative lesions are an important cause of morbidity among HIV- infected individuals, often causing serious difficulties in complying with therapeutic regimens and sufficient nutrient and fluid intake. Some of these ulcers represent aphthous stomatitis which usually responds well to corticosteroid treatment, while data from a number of laboratories suggest that human cytomegalovirus (HCMV), and possibly herpes simplex virus (HSV), are involved in the pathogenesis of other persistent oral ulcerations. In addition, necrotizing stomatitis, gingivitis and periodontitis are ulcerative lesions that not only have a bacterial component but also may demonstrate concurrent infection with HCMV and HSV. Unfortunately, the reports of these persistent oral ulcers, published to date, have involved relatively small numbers of patients. The research proposed in this project will attempt to determine the role of HCMV and other factors (e.g., HSV) in the development and progression of persistent oral ulcers. Sections from surgical specimens of chronic oral ulcerations which have not responded to empirical drug therapy will be examined for virus-induced cytopathic changes and the presence of virus-specific components by immunohistochemical methods, in situ hybridization, and the multiplex polymerase chain reaction (PCR) to identify the specific cell types and virus(es) that are involved in these lesions. Saliva from individuals afflicted with persistent oral lesions and from those without these lesions will be monitored for human herpesviruses by culture and by quantitative PCR. Individuals with demonstrated involvement of HCMV in their persistent oral ulcers will be treated with ganciclovir to evaluate the potential of this therapeutic approach to manage these lesions. The contribution of several mechanisms of cellular injury associated with HCMV infection to the development and progression of persistent oral ulcers will be examined in an effort to begin to better characterize the pathogenesis of these lesions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE011389-01
Application #
2132684
Study Section
Special Emphasis Panel (ZDE1-YS (33))
Project Start
1994-09-30
Project End
1998-09-29
Budget Start
1994-09-30
Budget End
1995-09-29
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Chen, Zhenping; Knutson, Eugene; Wang, Shuo et al. (2007) Stabilization of p53 in human cytomegalovirus-initiated cells is associated with sequestration of HDM2 and decreased p53 ubiquitination. J Biol Chem 282:29284-95
Deng, Cheng Z; Fons, Michael P; Rosenblatt, Judah et al. (2006) Nickel potentiates the genotoxic effect of benzo[a]pyrene in Chinese hamster lung V79 cells. Environ Mol Mutagen 47:150-61
Albrecht, Thomas; Deng, Cheng Zong; Abdel-Rahman, Sherif Z et al. (2004) Differential mutagen sensitivity of peripheral blood lymphocytes from smokers and nonsmokers: effect of human cytomegalovirus infection. Environ Mol Mutagen 43:169-78
Chen, Z; Knutson, E; Kurosky, A et al. (2001) Degradation of p21cip1 in cells productively infected with human cytomegalovirus. J Virol 75:3613-25
Bresnahan, W A; Albrecht, T; Thompson, E A (1998) The cyclin E promoter is activated by human cytomegalovirus 86-kDa immediate early protein. J Biol Chem 273:22075-82
Bresnahan, W A; Thompson, E A; Albrecht, T (1997) Human cytomegalovirus infection results in altered Cdk2 subcellular localization. J Gen Virol 78 ( Pt 8):1993-7
Boldogh, I; Bui, T K; Szaniszlo, P et al. (1997) Novel activation of gamma-interferon in nonimmune cells during human cytomegalovirus replication. Proc Soc Exp Biol Med 215:66-73
Bresnahan, W A; Boldogh, I; Chi, P et al. (1997) Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication. Virology 231:239-47
Bresnahan, W A; Boldogh, I; Ma, T et al. (1996) Cyclin E/Cdk2 activity is controlled by different mechanisms in the G0 and G1 phases of the cell cycle. Cell Growth Differ 7:1283-90
Boldogh, I; Szaniszlo, P; Bresnahan, W A et al. (1996) Kaposi's sarcoma herpesvirus-like DNA sequences in the saliva of individuals infected with human immunodeficiency virus. Clin Infect Dis 23:406-7

Showing the most recent 10 out of 11 publications