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Journal of virology1996; 70(11); 7842-7850; doi: 10.1128/JVI.70.11.7842-7850.1996

A primary production deficit in the thrombocytopenia of equine infectious anemia.

Abstract: The purpose of this study was to identify the mechanisms responsible for the thrombocytopenia that develops following infection of horses by the lentivirus equine infectious anemia virus (EIAV). Immunocompetent Arabian foals and Arabian foals with severe combined immunodeficiency (SCID), which lack functional B and T lymphocytes, were experimentally infected with EIAV. Levels of viremia and a number of clinical and hematologic parameters were examined prior to and following infection. Thrombocytopenia was not dependent on the immune response: SCID foals were affected as severely as immunocompetent foals. Production of platelets, measured by metabolic incorporation of radioactive label, was significantly reduced. The decrease ranged from 35 to 89% in three SCID and two immunocompetent foals examined. Platelet survival, measured by 51Cr labeling, also declined following infection in both SCID and immunocompetent foals: 51 and 68%, respectively, relative to the preinfection life spans. The difference between immunocompetent and immunodeficient foals was not statistically significant. The number of megakaryocytes (MK) per square millimeter of bone marrow, determined by digitizing morphometry, was not significantly altered in either SCID or immunocompetent thrombocytopenic foals. Numbers of denuded MK nuclei per unit area increased, but the elevation was not statistically significant. No evidence for viral replication in MK was found. Three different parameters of intravascular coagulation (activated prothombin time, fibrin degradation products, and one-step prothombin time) remained normal until after platelet numbers had declined significantly, arguing against an important role for disseminated intravascular coagulation. The findings indicate that EIAV induces thrombocytopenia principally through an indirect, noncytocidal suppressive effect on platelet production, the mechanism of which is unknown. A shortening of platelet life span apparently contributes moderately to the platelet deficit as well. The shortening of platelet life span is multifactorial in origin, including both mechanisms that depend on an active immune response and those that do not.
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Publication Date: 1996-11-01 PubMed ID: 8892906PubMed Central: PMC190855DOI: 10.1128/JVI.70.11.7842-7850.1996Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research study examines the decline in platelet production in horses after infection by the virus equine infectious anemia virus (EIAV). It concludes that the virus causes this decrease primarily through a non-lethal suppressive effect on platelet production rather than an active immune response.

Objectives of the Study

  • The aim of the research was to understand why there is a reduction in platelets (thrombocytopenia) after horses are infected by EIAV.

Methodology

  • Healthy Arabian foals and Arabian foals with severe combined immunodeficiency (SCID) – meaning they lack functional B and T lymphocytes – were infected with EIAV.
  • Levels of viremia and various clinical and hematologic parameters were measured before and after infection.
  • Platelet production was assessed by metabolic incorporation of radioactive label while platelet survival was evaluated using 51Cr labeling.
  • The number of megakaryocytes (MK), the platelet-forming cells in bone marrow, was determined via digitizing morphometry.
  • Different indicators of intravascular coagulation were also monitored.

Findings

  • The study found that thrombocytopenia was not dependent on the immune response as both SCID and healthy foals were affected to a similar degree.
  • Post-infection, platelet production was considerably decreased, ranging from a 35 to 89% reduction in different foals examined.
  • Moreover, platelet survival also fell following infection.
  • The number of MKs was not significantly altered, neither was the number of denuded MK nuclei per unit area.
  • No signs of viral replication in MKs were detected. Intravascular coagulation parameters remained normal until the drop in platelet numbers was significant, suggesting intravascular coagulation did not play a major role in the process.

Conclusion

  • The findings suggest that EIAV leads to thrombocytopenia mainly through a non-killing suppressive impact on platelet production. The reason behind this mechanism remains unknown.
  • A shortening of the platelet life span also contributes moderately to the reduction in platelets. This shortening is due to a variety of reasons, some of which depend on an active immune response and those that do not.

Cite This Article

APA
Crawford TB, Wardrop KJ, Tornquist SJ, Reilich E, Meyers KM, McGuire TC. (1996). A primary production deficit in the thrombocytopenia of equine infectious anemia. J Virol, 70(11), 7842-7850. https://doi.org/10.1128/JVI.70.11.7842-7850.1996

Publication

Journal of virology
ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 70
Issue: 11
Pages: 7842-7850

Researcher Affiliations

Crawford, T B
  • Department of Veterinary Microbiology, Washington State University, Pullman 99164-7040, USA. crawford@vetmed.wsu.edu.
Wardrop, K J
    Tornquist, S J
      Reilich, E
        Meyers, K M
          McGuire, T C

            MeSH Terms

            • Animals
            • Antigens, Viral / analysis
            • Blood Coagulation Factors
            • Blood Platelets / physiology
            • Blood Platelets / ultrastructure
            • Bone Marrow Cells
            • Equidae
            • Equine Infectious Anemia / blood
            • Equine Infectious Anemia / physiopathology
            • Equine Infectious Anemia / virology
            • Infectious Anemia Virus, Equine / growth & development
            • Infectious Anemia Virus, Equine / immunology
            • Megakaryocytes / ultrastructure
            • Platelet Count
            • Severe Combined Immunodeficiency
            • Thrombocytopenia / physiopathology
            • Thrombocytopenia / veterinary
            • Viremia

            Grant Funding

            • 2-T32-AI07025 / NIAID NIH HHS
            • HL 46651 / NHLBI NIH HHS

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            Citations

            This article has been cited 13 times.
            1. Taylor SD, Leib SR, Wu W, Nelson R, Carpenter S, Mealey RH. Protective effects of broadly neutralizing immunoglobulin against homologous and heterologous equine infectious anemia virus infection in horses with severe combined immunodeficiency. J Virol 2011 Jul;85(13):6814-8.
              doi: 10.1128/JVI.00077-11pubmed: 21543497google scholar: lookup
            2. Taylor SD, Leib SR, Carpenter S, Mealey RH. Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses. J Virol 2010 Jul;84(13):6536-48.
              doi: 10.1128/JVI.00218-10pubmed: 20392850google scholar: lookup
            3. Johns JL, Macnamara KC, Walker NJ, Winslow GM, Borjesson DL. Infection with Anaplasma phagocytophilum induces multilineage alterations in hematopoietic progenitor cells and peripheral blood cells. Infect Immun 2009 Sep;77(9):4070-80.
              doi: 10.1128/IAI.00570-09pubmed: 19564373google scholar: lookup
            4. Mealey RH, Littke MH, Leib SR, Davis WC, McGuire TC. Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: lack of correlation between in vitro activity and in vivo efficacy. Vet Immunol Immunopathol 2008 Jan 15;121(1-2):8-22.
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            5. Mealey RH, Sharif A, Ellis SA, Littke MH, Leib SR, McGuire TC. Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes. Virology 2005 Aug 15;339(1):110-26.
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            6. Mealey RH, Leib SR, Pownder SL, McGuire TC. Adaptive immunity is the primary force driving selection of equine infectious anemia virus envelope SU variants during acute infection. J Virol 2004 Sep;78(17):9295-305.
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            7. Mealey RH, Zhang B, Leib SR, Littke MH, McGuire TC. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus. Virology 2003 Sep 1;313(2):537-52.
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