The overall goal of this proposal is to characterize hematologic abnormalities in the feline acquired immunodeficiency syndrome (FAIDS) that is associated with the feline T-lymphotropic virus (FTLV) infection. FTLV is a newly described lentivirus that is structurally and biologically similar to, but antigenically distinct from, the human immunodeficiency virus (HIV). Cats infected with FTLV develop recurrent infections, diarrhea, neurological abnormalities, lymphopenia, neutropenia and anemia. We will study the interaction of FTLV and hematopoietic progenitors in vitro and in vivo. We will determine if progenitor cells (BFU-E or CFU- GM) are infected with FTLV, if they differentiate appropriately in culture, and if a serum factor or accessory cell inhibits in vitro hematopoiesis. In additional studies, cats with FTLV infection will be treated with trimethoprimsulfamethoxazole (TMP/SMX), azido-deoxythymidine (AZT) or other drugs, and we will determine the mechanism of marrow suppression should cytopenia develop. Finally, we will develop a long-term feline marrow culture system to study the interactions of progenitors, FTLV, and/or drugs in vitro. Our intent is to establish an animal model of the hematologic abnormalities in AIDS. Because blood and marrow samples can be obtained repeatedly from, cats, our model should allow prospective and longitudinal studies. In addition, as FTLV does not infect human cells or cell lines, these studies involve less biohazard than cell culture studies with blood or marrow from AIDS patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK041934-02
Application #
3242916
Study Section
Special Emphasis Panel (SRC (DB))
Project Start
1988-12-20
Project End
1993-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Linenberger, M L; Beebe, A M; Pedersen, N C et al. (1995) Marrow accessory cell infection and alterations in hematopoiesis accompany severe neutropenia during experimental acute infection with feline immunodeficiency virus. Blood 85:941-51
Shelton, G H; Linenberger, M L; Persik, M T et al. (1995) Prospective hematologic and clinicopathologic study of asymptomatic cats with naturally acquired feline immunodeficiency virus infection. J Vet Intern Med 9:133-40
Linenberger, M L; Abkowitz, J L (1995) Haematological disorders associated with feline retrovirus infections. Baillieres Clin Haematol 8:73-112
Linenberger, M L; Abkowitz, J L (1992) Studies in feline long-term marrow culture: hematopoiesis on normal and feline leukemia virus infected stromal cells. Blood 80:651-62
Shelton, G H; Linenberger, M L; Abkowitz, J L (1991) Hematologic abnormalities in cats seropositive for feline immunodeficiency virus. J Am Vet Med Assoc 199:1353-7
Linenberger, M L; Shelton, G H; Persik, M T et al. (1991) Hematopoiesis in asymptomatic cats infected with feline immunodeficiency virus. Blood 78:1963-8
Shelton, G H; Grant, C K; Linenberger, M L et al. (1990) Severe neutropenia associated with griseofulvin therapy in cats with feline immunodeficiency virus infection. J Vet Intern Med 4:317-9
Shelton, G H; Linenberger, M L; Grant, C K et al. (1990) Hematologic manifestations of feline immunodeficiency virus infection. Blood 76:1104-9