Abstract

.) While serious CMV infections can involve a number of host tissues, the lungs are frequently involved in lethal CMV infections. In these experiments several murine models of CMV infection will be utilized in order to explore the cytokines, TNF-a and lymphotoxin (TNF-b), as mediators of tissue damage. The role of TNF-a and b in acute MCMV infection following sublethal and lethal virus challenge will be examined. Using a model of acute CMV infection, the amount of TNF expressed in tissue during lethal and sublethal virus challenge will be compared and the effect of exogenous TNF on acute CMV infection will be monitored. The effects of passive transfer of antibody to TNF on virus replication will be determined. To explore the role of TNF in lung injury, a murine model of pneumocystis associated MCMV and graft-versus-host disease will be used, comparing the levels of TNF during MCMV lung infection and pneumocystis. The production of TNF by lung cells during pneumocystis will be examined and it will be determined if production is antigen-specific or MHC-restricted. The effects of passive transfer of antibody to TNF and lymphotoxin on MCMV pneumocystis will also be determined.
The Specific Aims of this project are: to determine the role of TNF-a and lymphotoxin in acute MCMV infection; and to determine the role of TNF-a and lymphotoxin in the pathogenesis of pneumocystis associated with combined MCMV infection and GVH disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL034813-05A1
Application #
3348185
Study Section
Pathology A Study Section (PTHA)
Project Start
1986-04-01
Project End
1993-11-30
Budget Start
1990-12-15
Budget End
1991-11-30
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Connecticut
Department
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030

  Publications

Almeida-Porada, G; Porada, C D; Shanley, J D et al. (1997) Altered production of GM-CSF and IL-8 in cytomegalovirus-infected, IL-1-primed umbilical cord endothelial cells. Exp Hematol 25:1278-85
Shanley, J D; Biegel, D; Pachter, J S (1996) A rapid and sensitive radioimmunoassay for the detection of human cytomegalovirus binding and infection of human fibroblasts. J Virol Methods 58:121-9
Wu, Q H; Ascensao, J; Almeida, G et al. (1994) The effect of short-chain fatty acids on the susceptibility of human umbilical vein endothelial cells to human cytomegalovirus infection. J Virol Methods 47:37-50
Wu, Q H; Trymbulak, W; Tatake, R J et al. (1994) Replication of human cytomegalovirus in cells deficient in beta 2-microglobulin gene expression. J Gen Virol 75 ( Pt 10):2755-9
Shanley, J D; Korngold, R; Forman, S J (1993) The effect of graft-versus-host disease in response to minor histocompatibility antigens on acute murine cytomegalovirus infection. Transplantation 56:487-9
Shanley, J D; Biczak, L; Forman, S J (1993) Acute murine cytomegalovirus infection induces lethal hepatitis. J Infect Dis 167:264-9
Shanley, J D (1990) In vivo administration of monoclonal antibody to the NK 1.1 antigen of natural killer cells: effect on acute murine cytomegalovirus infection. J Med Virol 30:58-60
Erlich, K S; Mills, J; Shanley, J D (1989) Effects of L3T4+ lymphocyte depletion on acute murine cytomegalovirus infection. J Gen Virol 70 ( Pt 7):1765-71
Shanley, J D; Debs, R J (1989) The folate antagonist, methotrexate, is a potent inhibitor of murine and human cytomegalovirus in vitro. Antiviral Res 11:99-106
Shanley, J D; Pomeroy, C; Via, C S et al. (1988) Interstitial pneumonitis during murine cytomegalovirus infection and graft-versus-host reaction: effect of ganciclovir therapy. J Infect Dis 158:1391-4

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