Immune-mediated thrombocytopenia in horses infected with equine infectious anemia virus.
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 antibody-coated platelets from the peripheral circulation by hepatic Kupffer 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.
Clabough
D L
DL
Department of Microbiology, Pathology and Parasitology, North Carolina State University College of Veterinary Medicine, Raleigh 27606.
Gebhard
D
D
Flaherty
M T
MT
Whetter
L E
LE
Perry
S T
ST
Coggins
L
L
Fuller
F J
FJ
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000502:physiology; D015153:Blotting, Western; D001853:Bone Marrow / Q000382:microbiology / Q000473:pathology; D003001:Cloning, Molecular; D004859:Equine Infectious Anemia / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D005455:Fluorescent Antibody Technique; D015750:Genes, gag; D006736:Horses; D004860:Infectious Anemia Virus, Equine / Q000235:genetics / Q000302:isolation & purification*; D009693:Nucleic Acid Hybridization; D010976:Platelet Count; D015347:RNA Probes; D012194:RNA-Directed DNA Polymerase / Q000097:blood; D015183:Restriction Mapping; D013921:Thrombocytopenia / Q000276:immunology*
D015415:Biomarkers; D015347:RNA Probes; D012194:RNA-Directed DNA Polymerase