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 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.
Publication Date: 1991-11-01 PubMed ID: 1717720PubMed Central: PMC250322DOI: 10.1128/JVI.65.11.6242-6251.1991Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research article investigates the cause of low platelet count in horses that’s associated with fever, during an infection known as Equine Infectious Anemia Virus (EIAV). The study suggests that this reduction in platelet count is a result of an immune response, potentially involving the creation of immune complexes on platelets, rather than direct viral attack.
Problem description
- The problem investigated in this study is the depressive effect on platelet count (a condition known as thrombocytopenia) in horses during episodes of fever in an infection of Equine Infectious Anemia Virus (EIAV).
- The researchers noticed a cyclical pattern where the lowest platelet count (nadir) coincided with the maximum fever (peak febrile responses).
Methodology
- To delve deeper into this phenomenon, the researchers experimented on four adult horses, infecting them with the wild-type Wyoming strain of EIAV.
- The effects of the infection on the platelet count and rectal temperature was monitored.
- Moreover, the researchers assessed the serum reverse transcriptase activity, a marker of viral replication, and checked for an EIAV-specific immune response through a Western immunoblot, a technique used to detect specific proteins in a sample.
- The researchers pointedly examined increases in platelet-associated immunoglobulins G and M, as they could indicate an immune response. This was done through a direct fluorescent-antibody test and flow cytometric assay, both tools for identifying and measuring physical and chemical characteristics of a population of cells or particles.
- Notably, the researchers also examined the bone marrow megakaryocytes (cells involved in platelet production) for viral replication using in situ hybridization, a technique for localizing specific DNA or RNA sequences in portions of cells or tissues.
Findings
- The study found that there was indeed a decrease in platelet count as rectal temperature increased in the horses infected with EIAV.
- There was also an increase in serum reverse transcriptase activity which coincided with a rise in rectal temperature.
- By day 10 post-infection, all horses developed an EIAV-specific immune response and a detectable increase in platelet-associated immunoglobulins G and M.
- Conversely, viral replication was not detected in the bone marrow megakaryocytes.
- These results suggest that the thrombocytopenia observed in EIAV-infected horses is immune-mediated rather than being directly caused by viral replication within platelet-producing cells.
Proposed mechanism
- The researchers propose that the thrombocytopenia and fever cycle is related to the deposition of immune complexes on platelets, even though they could not directly identify virion particles in association with platelet-bound antibody.
- These immune complexes may be cleared by hepatic Kupffer cells and splenic macrophages, which are components of the body’s immune system capable of phagocytosis, or cell “eating”.
- The targeting and clearance of these immune complexes could inadvertently aid the spread of the virus within the body by targeting virus particles to the host cells that are most susceptible to virus replication.
Cite This Article
APA
Clabough DL, Gebhard D, Flaherty MT, Whetter LE, Perry ST, Coggins L, Fuller FJ.
(1991).
Immune-mediated thrombocytopenia in horses infected with equine infectious anemia virus.
J Virol, 65(11), 6242-6251.
https://doi.org/10.1128/JVI.65.11.6242-6251.1991 Publication
Researcher Affiliations
- Department of Microbiology, Pathology and Parasitology, North Carolina State University College of Veterinary Medicine, Raleigh 27606.
MeSH Terms
- Animals
- Biomarkers / blood
- Blood Platelets / physiology
- Blotting, Western
- Bone Marrow / microbiology
- Bone Marrow / pathology
- Cloning, Molecular
- Equine Infectious Anemia / blood
- Equine Infectious Anemia / immunology
- Equine Infectious Anemia / microbiology
- Fluorescent Antibody Technique
- Genes, gag
- Horses
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / isolation & purification
- Nucleic Acid Hybridization
- Platelet Count
- RNA Probes
- RNA-Directed DNA Polymerase / blood
- Restriction Mapping
- Thrombocytopenia / immunology
Grant Funding
- 1K11-AI00963 / NIAID NIH HHS
- R01-AI24904 / NIAID NIH HHS
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