Many ocular diseases of cytomegalovirus (CMV) in humans are opportunistic infections of the eye and occur predominantly in immunosuppressed individuals. As the number of immunosuppressed patients increases in recent years due largely to acquired immunodeficiency syndrome (AIDS), CMV has become the causal agent for an important eye disease. Yet, the pathogenesis of CMV eye infection is poorly understood at present. In view of ten serious nature of CMV eye infection and even increasing incidence of CMV eye infection among AIDS patients, a critical assessment of the role of CMV in human eye infection as well as a comprehensive study of the nature of the disease are urgently needed. Our preliminary studies on murine CMV (MCMV) eye infection clearly showed that as in humans, the intact host cellular immunity is an important factor for the protection of the mouse from the infection and recurrence of MCMV. Therefore, as our initial efforts to evaluate the effect of host cellular immunity on the pathogenesis of CMV eye infection, the following series of experiments is proposed: 1) Roles of various cellular immune components of the mouse, namely helper T cells (L3T4+ cells), suppressor T cells (Lyt-2+ cells), natural killer cells and macrophages in the induction of viremia and primary eye infection during systemic infection of MCMV will be studied. 2) The establishment of latency of MCMV in the eye and macrophages following primary infection will be examined, and the location of the virus genomes in the eye tissues will be determined by means of co-culture method and DNA-DNA hybridization techniques with MCMV-DNA probes. 3) Cellular immune components which may be responsible for in vivo reactivation of latent MCMV in the eye will be identified by evaluating the effect of selective depletion of each immune component on the reactivation of the latent virus. The proposed study will provide us hitherto unavailable information on CMV eye infection which will shed some light on our understanding of pathogenesis of the disease and also will assist us in the search for effective means for the prevention and treatment of CMV infections in humans.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008037-03
Application #
3265146
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1989-05-01
Project End
1994-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Inoue, Y; Minasi, P; Oh, J O (1993) The role of natural killer cells in murine cytomegalovirus eye infection. Invest Ophthalmol Vis Sci 34:1954-62
Inoue, Y; Oh, J O; Minasi, P (1991) Protective effect of anti-glycoprotein D antibody on herpetic chorioretinitis in newborn rabbits. Curr Eye Res 10 Suppl:159-65
Rabinovitch, T; Oh, J O; Minasi, P (1990) In vivo reactivation of latent murine cytomegalovirus in the eye by immunosuppressive treatment. Invest Ophthalmol Vis Sci 31:657-63