The applicants propose to utilize the feline immunodeficiency virus (FIV) cat animal model for AIDS to develop a better understanding of the pathogenesis of lentivirus-mediated thymic involution and thymic impairment, and the contribution of thymic lymphopoiesis to immune homeostasis in lentivirus-infected subjects. The pediatric FIV model shows lymph node and thymic lesions similar to those reported in human pediatric AIDS. FIV-infected pediatric and adult cats also have loss of recall antigen responses. Work in their laboratory suggest that in pediatric cats antiviral drug therapy during the acute stage of infection can prevent the loss of T-cells possibly by protecting thymic lymphopoiesis during early life. Further they have evidence from preliminary studies in FIV-infected adults cats, that antiviral therapy stimulates thymic hematopoiesis in a pattern compatible with restoration of thymic T-cell processing. For this proposal, they submit the following specific aims: 1. To measure the contribution of thymic lymphopoiesis to a) the maintenance of peripheral blood T-lymphocyte homeostasis; b) replenishment of T-helper cells depleted by FIV infection and c) regeneration of recall antigen responses lost during FIV infection. 2) To determine if antiviral therapy can: a) prevent thymic involution and loss of thymic lymphopoiesis in FIV-infected pediatric cats; b) allow for reestablishment of thymic lymphopoiesis and restoration of the recall antigen T-cell response in FIV-infected adult cats.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI040855-03
Application #
2882218
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Program Officer
Litterst, Charles L
Project Start
1997-03-01
Project End
2001-02-28
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Ohio State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Hayes, Kathleen A; Koksoy, Sadi; Phipps, Andrew J et al. (2005) Lentivirus-specific cytotoxic T-lymphocyte responses are rapidly lost in thymectomized cats infected with feline immunodeficiency virus. J Virol 79:8237-42
Francke, Sabine; Orosz, Charles G; Hsu, Jason et al. (2002) Immunomodulatory effect of zidovudine (ZDV) on cytotoxic T lymphocytes previously exposed to ZDV. Antimicrob Agents Chemother 46:2865-71
Koksoy, S; Phipps, A J; Hayes, K A et al. (2001) SV40 Immortalization of feline fibroblasts as targets for MHC-restricted cytotoxic T-cell assays. Vet Immunol Immunopathol 79:285-95
Hayes, K A; Phipps, A J; Francke, S et al. (2000) Antiviral therapy reduces viral burden but does not prevent thymic involution in young cats infected with feline immunodeficiency virus. Antimicrob Agents Chemother 44:2399-405
Francke, S; Orosz, C G; Hayes, K A et al. (2000) Effect of zidovudine on the primary cytolytic T-lymphocyte response and T-cell effector function. Antimicrob Agents Chemother 44:1900-5
Phipps, A J; Hayes, K A; Buck, W R et al. (2000) Neurophysiologic and immunologic abnormalities associated with feline immunodeficiency virus molecular clone FIV-PPR DNA inoculation. J Acquir Immune Defic Syndr 23:16-Aug