The mechanisms operative in production of the thrombocytopenia that is a characteristic feature of equine infectious anemia (EIA) will be studied using genetically immunodeficient CID foals. The main questions revolve around the relative roles of direct viral damage compared to immunologic injury in the thrombocytopenia of this lentiviral infection. The questions this research will answer are: 1) Is the platelet deficiency a result of immunologic damage or a direct effect of viral activity? 2) Is the basis of the thrombocytopenia a lack of production or shortened platelet survival? 3) If the mechanism is immunologic in nature, what are the target antigens involved? and 4) Is the immunologic damage mediated solely by antibody? CID foals are fully susceptible to the EIA lentivirus but lack the ability to mount any immune responses to the agent. They provide a uniquely powerful model system that can generate unequivocal answers to these important questions. The experimental design uses groups of five age-matched foals: Immunocompetent infected and uninfected, and immunodeficient infected and uninfected. The animals will be infected and the effects on the platelet system examined in a number of ways. Kinetic studies using radioisotope tracers will measure platelet production and life spans. The presence or absence of viral antigens and immunoglobulin on platelets will be determined. The specificity of any immunoglobulin present on the platelet surface will be examined. With regard to megakaryocytes, their numbers, ultrastructural changes, and presence of viral antigen and immunoglobulin will be followed. If immunologic mechanisms are implicated by early experiments, passive antibody transfer experiments will be performed to prove that the humoral arm of the immune response is responsible.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL046651-02
Application #
3365757
Study Section
Special Emphasis Panel (SRC (JI))
Project Start
1991-03-10
Project End
1993-12-31
Budget Start
1992-01-15
Budget End
1992-12-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Washington State University
Department
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
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Crawford, T B; Wardrop, K J; Tornquist, S J et al. (1996) A primary production deficit in the thrombocytopenia of equine infectious anemia. J Virol 70:7842-50
Wardrop, K J; Baszler, T V; Reilich, E et al. (1996) A morphometric study of bone marrow megakaryocytes in foals infected with equine infectious anemia virus. Vet Pathol 33:222-7
Wiler, R; Leber, R; Moore, B B et al. (1995) Equine severe combined immunodeficiency: a defect in V(D)J recombination and DNA-dependent protein kinase activity. Proc Natl Acad Sci U S A 92:11485-9