Feline leukemia pathogenesis presents a well characterized model of retrovirus-mediated disease resulting in either a progressive chronic viremia with immune suppression and malignancy or a regressive disease without apparent retroviral damage. Factors other than virus inoculum, strain and age related susceptibility which lead to viral persistence in the host are obscure. In this multifaceted study, we propose to examine the critical immunological and nonspecific events which predispose the host to disease progression.
The specific aims are: to examine the role of cell membrane FeLV-induced changes on cell function and cell-cell recognition interactions necessary for developing adequate host protection; to compare the immune response in progressor and regressor cats by studying phagocytic and intracellular killing mechanisms, production of immune modulators such as interferon and prostaglandins, and examining the role of immune complex formation on pathogenesis and immunomodulation; and last to ascertain whether transient or latent undetectable FeLV infection in cats produces long term hemolymphatic defects which may become evident during subsequent concomitant disease or immunosuppressive drug treatment. Methods for studying these parameters include: Percoll separation of hemolymphatic cells; antibody-ELISA on cells for identification or retroviral-induced cell membrane changes; cell affinity chromatographic separation of altered cells for functional studies; detection of Ia-like antigen expression and subsequent changes after infection by use of the feline MLR; titration of prostaglandin production and cellular levels of cAMP and cGMP by RIA; C1q ELISA assay for detection of circulating immune complexes; and the use of Staph Protein A columns for isolation of CIC for analysis and in vitro cell function assay, lymphocyte blast transformation and phagocytosis assays.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA030338-06
Application #
3169224
Study Section
Experimental Immunology Study Section (EI)
Project Start
1981-09-01
Project End
1988-03-31
Budget Start
1986-07-01
Budget End
1988-03-31
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Veterinary Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Williams, L L; Lewis, M G; Olsen, R G et al. (1993) Chronic feline leukemia virus infection alters arachidonic acid proportions in vivo and in vitro. Proc Soc Exp Biol Med 202:239-45
Dezzutti, C S; Lafrado, L J; Lewis, M G et al. (1990) Inhibition of phorbol ester-induced neutrophil chemiluminescence by FeLV. Arch Virol 111:75-85
Lafrado, L J; Mathes, L E; Zack, P M et al. (1990) Biological effects of staphylococcal protein A immunotherapy in cats with induced feline leukemia virus infection. Am J Vet Res 51:482-6
Copelan, E A; Waddell, K S; Johnson, S C et al. (1990) Purine metabolism in feline lymphomas. Vet Pathol 27:117-21
Dezzutti, C S; Wright, K A; Lewis, M G et al. (1989) FeLV-induced immunosuppression through alterations in signal transduction: down regulation of protein kinase C. Vet Immunol Immunopathol 21:55-67
Lafrado, L J; Dezzutti, C S; Lewis, M G et al. (1989) Immunodeficiency in latent feline leukemia virus infections. Vet Immunol Immunopathol 21:39-46
Lewis, M G; Lafrado, L J; Haffer, K et al. (1988) Feline leukemia virus vaccine: new developments. Vet Microbiol 17:297-308
Bauer, R M; Olsen, R G (1988) Parameters of production and partial characterization of feline interleukin 2. Vet Immunol Immunopathol 19:173-83
Lewis, M G; Wright, K A; Lafrado, L J et al. (1987) Saliva as a source of feline leukemia virus antigen for diagnosis of disease. J Clin Microbiol 25:1320-2
Olsen, R G; Lewis, M G; Lafrado, L J et al. (1987) Feline leukemia virus: current status of the feline induced immune depression and immunoprevention. Cancer Metastasis Rev 6:243-60

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