Immune-mediated thrombocytopenia in horses infected with equine infectious anemia virus

Abstract

An adult horse infected with a virulent, cell culture-adapted strain of equine infectious anemia virus (EIAV) developed cyclical thrombocytopenia in which the nadir of platelet counts coincided with peak febrile responses. In order to investigate the mechanism of thrombocytopenia during acute febrile episodes, four adult horses were experimentally infected with the wild-type Wyoming strain of EIAV. Platelet counts decreased from baseline as rectal temperature increased. Serum reverse transcriptase activity increased above background levels in all horses, coincident with increase in rectal temperature. All horses developed an EIAV-specific immune response detectable by Western immunoblot by postinfection day 10. Increases in platelet-associated immunoglobulins G and M were detectable by direct fluorescent-antibody test and flow cytometric assay. Viral replication in bone marrow megakaryocytes was not detectable by in situ hybridization. Results suggest an immune-mediated mechanism of thrombocytopenia in horses infected with EIAV. Despite an inability to identify virion particles in association with platelet-bound antibody, the cyclical nature of the thrombocytopenia and the occurrence of a marked cell-free viremia concomitant with fever and thrombocytopenia suggest immune complex deposition on platelets. We propose that clearance of virus and antibodycoated platelets from the peripheral circulation by hepatic Kupifer cells and splenic macrophages may target infectious virus particles, in the form of immune complexes, to host cells most permissive for in vivo viral replication. * Corresponding author. and for platelet-associated virus. We have also examined bone marrow for the presence of viral replication in megakaryocytes or megakaryocyte depletion.

The immunopathogenesis of equine infectious anemia virus

“…During thrombocytopenia, circulating platelets have increased quantities of platelet-bound IgG and IgM (Clabough et al, 1991). Viral replication in bone marrow megakaryocytes is not detectable by in situ hybridization (Clabough et al, 1991). These results suggest that immune complexes are deposited on platelets, facilitating their removal from circulation by mononuclear phagocytes of the spleen and liver.…”

“…Hemorrhage and edema have been attributed to vascular changes, especially in vascular mesenchymal tissues (Konno and Ya-mamoto, 1970). Severe thrombocytopenia during febrile episodes may also contribute to petechial and ecchymotic hemorrhages (Clabough et al, 1991).…”

“…Thrombocytopenia is the earliest and most consistent laboratory abnormality observed in febrile horses (Clabough et al, 1991). Platelet counts start to decline prior to any increase in rectal temperature.…”

“…Sequential febrile episodes are associated with cyclical thrombocytopenia in which the nadir of platelet counts coincides with peak febrile responses. During thrombocytopenia, circulating platelets have increased quantities of platelet-bound IgG and IgM (Clabough et al, 1991). Viral replication in bone marrow megakaryocytes is not detectable by in situ hybridization (Clabough et al, 1991).…”

Equine Infectious Anemia

“…In some horses experimentally infected with virulent virus, a decrease in circulating platelet count is the only abnormality noted d uring the initial viremic episode. Thrombocytopenia recurs with subsequent febrile episodes, generally persists throughout the viremic period, and may become severe enough to cause hemorrhage, especially epistaxis or petechial hemorrhages of mucous membranesY, 13,44 Platelet counts usually rebound rapidly fo llowing resolution of viremiaY Decreases in packed cell volume and total erythrocyte count may become evident as early as 3 to 5 days postinfection and may become severe during the initial febrile episodes. 83 It is more common, however, for severe anemia to be seen in horses undergoing multiple febrile episodes.…”