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Journal of virology1991; 65(11); 6242-6251; doi: 10.1128/JVI.65.11.6242-6251.1991

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

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 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

ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 65
Issue: 11
Pages: 6242-6251

Researcher Affiliations

Clabough, D L
  • Department of Microbiology, Pathology and Parasitology, North Carolina State University College of Veterinary Medicine, Raleigh 27606.
Gebhard, D
    Flaherty, M T
      Whetter, L E
        Perry, S T
          Coggins, L
            Fuller, F J

              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

              References

              This article includes 41 references
              1. Casey JM, Kim Y, Andersen PR, Watson KF, Fox JL, Devare SG. Human T-cell lymphotropic virus type III: immunologic characterization and primary structure analysis of the major internal protein, p24.. J Virol 1985 Aug;55(2):417-23.
                pubmed: 2410630doi: 10.1128/JVI.55.2.417-423.1985google scholar: lookup
              2. Edington N, Bridges CG, Patel JR. Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: equine stroke.. Arch Virol 1986;90(1-2):111-24.
                pubmed: 3015074doi: 10.1007/BF01314149google scholar: lookup
              3. Zucker-Franklin D, Cao YZ. Megakaryocytes of human immunodeficiency virus-infected individuals express viral RNA.. Proc Natl Acad Sci U S A 1989 Jul;86(14):5595-9.
                pubmed: 2748605doi: 10.1073/pnas.86.14.5595google scholar: lookup
              4. Karpatkin S, Nardi MA, Hymes KB. Immunologic thrombocytopenic purpura after heterosexual transmission of human immunodeficiency virus (HIV).. Ann Intern Med 1988 Aug 1;109(3):190-3.
                pubmed: 3389601doi: 10.7326/0003-4819-109-3-190google scholar: lookup
              5. Lazarchick J, Hall SA. Platelet-associated IgG assay using flow cytometric analysis.. J Immunol Methods 1986 Mar 13;87(2):257-65.
                pubmed: 3512726doi: 10.1016/0022-1759(86)90540-5google scholar: lookup
              6. Bel-Ali Z, Dufour V, Najean Y. Platelet kinetics in human immunodeficiency virus induced thrombocytopenia.. Am J Hematol 1987 Dec;26(4):299-304.
                pubmed: 3687929doi: 10.1002/ajh.2830260402google scholar: lookup
              7. Axthelm MK, Krakowka S. Canine distemper virus-induced thrombocytopenia.. Am J Vet Res 1987 Aug;48(8):1269-75.
                pubmed: 3631719
              8. Neiman JC, Mant MJ, Shnitka TK. Phagocytosis of platelets by Kupffer cells in immune thrombocytopenia.. Arch Pathol Lab Med 1987 Jun;111(6):563-5.
                pubmed: 3579514
              9. . Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 46-1985. A 32-year-old woman with a cystic hepatic mass.. N Engl J Med 1985 Nov 14;313(20):1275-82.
                pubmed: 4058508doi: 10.1056/NEJM198511143132007google scholar: lookup
              10. Landonio G, Galli M, Nosari A, Lazzarin A, Cipriani D, Crocchiolo P, Voltolin L, Giannelli F, Irato L, De Cataldo F. HIV-related severe thrombocytopenia in intravenous drug users: prevalence, response to therapy in a medium-term follow-up, and pathogenetic evaluation.. AIDS 1990 Jan;4(1):29-34.
                pubmed: 2156528
              11. Sthoeger D, Nardi M, Travis S, Karpatkin M, Karpatkin S. Micromethod for demonstrating increased platelet surface immunoglobulin G: findings in acute, chronic, and human immunodeficiency virus-1-related immunologic thrombocytopenias.. Am J Hematol 1990 Aug;34(4):275-82.
                pubmed: 2368694doi: 10.1002/ajh.2830340408google scholar: lookup
              12. Zucker-Franklin D, Seremetis S, Zheng ZY. Internalization of human immunodeficiency virus type I and other retroviruses by megakaryocytes and platelets.. Blood 1990 May 15;75(10):1920-3.
                pubmed: 2337668
              13. Montelaro RC, Parekh B, Orrego A, Issel CJ. Antigenic variation during persistent infection by equine infectious anemia virus, a retrovirus.. J Biol Chem 1984 Aug 25;259(16):10539-44.
                pubmed: 6206055
              14. Payne SL, Salinovich O, Nauman SM, Issel CJ, Montelaro RC. Course and extent of variation of equine infectious anemia virus during parallel persistent infections.. J Virol 1987 Apr;61(4):1266-70.
              15. Salinovich O, Payne SL, Montelaro RC, Hussain KA, Issel CJ, Schnorr KL. Rapid emergence of novel antigenic and genetic variants of equine infectious anemia virus during persistent infection.. J Virol 1986 Jan;57(1):71-80.
                pubmed: 3001367doi: 10.1128/JVI.57.1.71-80.1986google scholar: lookup
              16. Stephens RM, Casey JW, Rice NR. Equine infectious anemia virus gag and pol genes: relatedness to visna and AIDS virus.. Science 1986 Feb 7;231(4738):589-94.
                pubmed: 3003905doi: 10.1126/science.3003905google scholar: lookup
              17. Sentsui H, Kono Y. Phagocytosis of horse erythrocytes treated with equine infectious anemia virus by cultivated horse leukocytes.. Arch Virol 1987;95(1-2):67-77.
                pubmed: 3036046doi: 10.1007/BF01311335google scholar: lookup
              18. Sentsui H, Kono Y. Complement-mediated hemolysis of horse erythrocytes treated with equine infectious anemia virus.. Arch Virol 1987;95(1-2):53-66.
                pubmed: 3036045doi: 10.1007/BF01311334google scholar: lookup
              19. Takeda A, Tuazon CU, Ennis FA. Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry.. Science 1988 Oct 28;242(4878):580-3.
                pubmed: 2972065doi: 10.1126/science.2972065google scholar: lookup
              20. Ault KA. Flow cytometric measurement of platelet-associated immunoglobulin.. Pathol Immunopathol Res 1988;7(5):395-408.
                pubmed: 3068668doi: 10.1159/000157132google scholar: lookup
              21. Kemeny LJ, Mott LO, Pearson JE. Titration of equine infectious anemia virus. Effect of dosage on incubation time and clinical signs.. Cornell Vet 1971 Oct;61(4):687-95.
                pubmed: 4330637
              22. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.. Nature 1970 Aug 15;227(5259):680-5.
                pubmed: 5432063doi: 10.1038/227680a0google scholar: lookup
              23. McGuire TC, Henson JB, Quist SE. Impaired bone marrow response in equine infectious anemia.. Am J Vet Res 1969 Dec;30(12):2099-104.
                pubmed: 5389416
              24. McGuire TC, Henson JB, Quist SE. Viral-induced hemolysis in equine infectious anemia.. Am J Vet Res 1969 Dec;30(12):2091-7.
                pubmed: 5389415
              25. Orrego A, Issel CJ, Montelaro RC, Adams WV Jr. Virulence and in vitro growth of a cell-adapted strain of equine infectious anemia virus after serial passage in ponies.. Am J Vet Res 1982 Sep;43(9):1556-60.
                pubmed: 6293349
              26. Walsh CM, Nardi MA, Karpatkin S. On the mechanism of thrombocytopenic purpura in sexually active homosexual men.. N Engl J Med 1984 Sep 6;311(10):635-9.
                pubmed: 6540841doi: 10.1056/NEJM198409063111004google scholar: lookup
              27. Issel CJ, Coggins L. Equine infectious anemia: current knowledge.. J Am Vet Med Assoc 1979 Apr 1;174(7):727-33.
                pubmed: 218920
              28. Sentsui H, Kono Y. Hemagglutination by equine infectious anemia virus.. Infect Immun 1976 Aug;14(2):325-31.
                pubmed: 9361doi: 10.1128/iai.14.2.325-331.1976google scholar: lookup
              29. Gonda MA, Charman HP, Walker JL, Coggins L. Scanning and transmission electron microscopic study of equine infectious anemia virus.. Am J Vet Res 1978 May;39(5):731-40.
                pubmed: 215061
              30. Perryman LE, McGuire TC, Banks KL, Henson JB. Decreased C3 levels in a chronic virus infection: equine infectious anemia.. J Immunol 1971 Apr;106(4):1074-8.
                pubmed: 4101772
              31. McGuire TC, Crawford TB, Henson JB. Equine infectious anemia: detection of infections virus-antibody complexes in the serum.. Immunol Commun 1972;1(6):545-51.
                pubmed: 4141690doi: 10.3109/08820137209022963google scholar: lookup
              32. McGuire TC, Henson JB, Burger D. Complement (C'3)-coated red blood cells following infection with the virus of equine infectious anemia.. J Immunol 1969 Aug;103(2):293-9.
                pubmed: 4184824
              33. Banks KL, Henson JB, McGuire TC. Immunologically mediated glomerulitis of horses. I. Pathogenesis in persistent infection by equine infectious anemia virus.. Lab Invest 1972 Jun;26(6):701-7.
                pubmed: 4337973
              34. Sakaguchi M, Sato T, Groopman JE. Human immunodeficiency virus infection of megakaryocytic cells.. Blood 1991 Feb 1;77(3):481-5.
                pubmed: 1991165
              35. Bourinbaiar AS, Phillips DM. Transmission of human immunodeficiency virus from monocytes to epithelia.. J Acquir Immune Defic Syndr (1988) 1991;4(1):56-63.
                pubmed: 1984056
              36. Whetter L, Archambault D, Perry S, Gazit A, Coggins L, Yaniv A, Clabough D, Dahlberg J, Fuller F, Tronick S. Equine infectious anemia virus derived from a molecular clone persistently infects horses.. J Virol 1990 Dec;64(12):5750-6.
              37. Visentin GP, Wolfmeyer K, Newman PJ, Aster RH. Detection of drug-dependent, platelet-reactive antibodies by antigen-capture ELISA and flow cytometry.. Transfusion 1990 Oct;30(8):694-700.
              38. Karpatkin S, Nardi M, Lennette ET, Byrne B, Poiesz B. Anti-human immunodeficiency virus type 1 antibody complexes on platelets of seropositive thrombocytopenic homosexuals and narcotic addicts.. Proc Natl Acad Sci U S A 1988 Dec;85(24):9763-7.
                pubmed: 3200854doi: 10.1073/pnas.85.24.9763google scholar: lookup
              39. Savona S, Nardi MA, Lennette ET, Karpatkin S. Thrombocytopenic purpura in narcotics addicts.. Ann Intern Med 1985 Jun;102(6):737-41.
                pubmed: 2986504doi: 10.7326/0003-4819-102-6-737google scholar: lookup
              40. Perryman LE, O'Rourke KI, McGuire TC. Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection.. J Virol 1988 Aug;62(8):3073-6.
              41. Corapi WV, French TW, Dubovi EJ. Severe thrombocytopenia in young calves experimentally infected with noncytopathic bovine viral diarrhea virus.. J Virol 1989 Sep;63(9):3934-43.

              Citations

              This article has been cited 21 times.
              1. Romo-Sáenz CI, Tamez-Guerra P, Olivas-Holguin A, Ramos-Zayas Y, Obregón-Macías N, González-Ochoa G, Zavala-Díaz de la Serna FJ, Rodríguez-Padilla C, Tamez-Guerra R, Gomez-Flores R. Molecular detection of equine infectious anemia virus in clinically normal, seronegative horses in an endemic area of Mexico. J Vet Diagn Invest 2021 Jul;33(4):758-761.
                doi: 10.1177/10406387211006195pubmed: 33797316google scholar: lookup
              2. Satué K, Gardon JC, Muñoz A. Clinical and laboratorial description of the differential diagnoses of hemostatic disorders in the horse. Iran J Vet Res 2020 Winter;21(1):1-8.
                pubmed: 32368218
              3. Durand S, Cimarelli A. The inside out of lentiviral vectors. Viruses 2011 Feb;3(2):132-159.
                doi: 10.3390/v3020132pubmed: 22049307google scholar: lookup
              4. Hines R, Sorensen BR, Shea MA, Maury W. PU.1 binding to ets motifs within the equine infectious anemia virus long terminal repeat (LTR) enhancer: regulation of LTR activity and virus replication in macrophages. J Virol 2004 Apr;78(7):3407-18.
              5. Rue SM, Roos JW, Amzel LM, Clements JE, Barber SA. Hydrogen bonding at a conserved threonine in lentivirus capsid is required for virus replication. J Virol 2003 Jul;77(14):8009-18.
              6. Overholser ED, Coleman GD, Bennett JL, Casaday RJ, Zink MC, Barber SA, Clements JE. Expression of simian immunodeficiency virus (SIV) nef in astrocytes during acute and terminal infection and requirement of nef for optimal replication of neurovirulent SIV in vitro. J Virol 2003 Jun;77(12):6855-66.
              7. Barber SA, Bruett L, Douglass BR, Herbst DS, Zink MC, Clements JE. Visna virus-induced activation of MAPK is required for virus replication and correlates with virus-induced neuropathology. J Virol 2002 Jan;76(2):817-28.
                doi: 10.1128/jvi.76.2.817-828.2002pubmed: 11752171google scholar: lookup
              8. Bruett L, Clements JE. Functional murine leukemia virus vectors pseudotyped with the visna virus envelope show expanded visna virus cell tropism. J Virol 2001 Dec;75(23):11464-73.
              9. Nunez R, Gomes-Keller MA, Schwarzwald C, Feige K. Assessment of Equine Autoimmune Thrombocytopenia (EAT) by flow cytometry. BMC Blood Disord 2001;1(1):1.
                doi: 10.1186/1471-2326-1-1pubmed: 11313001google scholar: lookup
              10. Maury W, Oaks JL, Bradley S. Equine endothelial cells support productive infection of equine infectious anemia virus. J Virol 1998 Nov;72(11):9291-7.
              11. Flaherty MT, Hauer DA, Mankowski JL, Zink MC, Clements JE. Molecular and biological characterization of a neurovirulent molecular clone of simian immunodeficiency virus. J Virol 1997 Aug;71(8):5790-8.
              12. Maury W, Perryman S, Oaks JL, Seid BK, Crawford T, McGuire T, Carpenter S. Localized sequence heterogeneity in the long terminal repeats of in vivo isolates of equine infectious anemia virus. J Virol 1997 Jul;71(7):4929-37.
              13. Crawford TB, Wardrop KJ, Tornquist SJ, Reilich E, Meyers KM, McGuire TC. A primary production deficit in the thrombocytopenia of equine infectious anemia. J Virol 1996 Nov;70(11):7842-50.
              14. Sellon DC, Walker KM, Russell KE, Perry ST, Covington P, Fuller FJ. Equine infectious anemia virus replication is upregulated during differentiation of blood monocytes from acutely infected horses. J Virol 1996 Jan;70(1):590-4.
                doi: 10.1128/JVI.70.1.590-594.1996pubmed: 8523576google scholar: lookup
              15. Sellon DC. Equine infectious anemia. Vet Clin North Am Equine Pract 1993 Aug;9(2):321-36.
                doi: 10.1016/s0749-0739(17)30399-1pubmed: 8395326google scholar: lookup
              16. McGuire TC, Tumas DB, Byrne KM, Hines MT, Leib SR, Brassfield AL, O'Rourke KI, Perryman LE. Major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes from horses with equine infectious anemia virus recognize Env and Gag/PR proteins. J Virol 1994 Mar;68(3):1459-67.
              17. Maury W. Monocyte maturation controls expression of equine infectious anemia virus. J Virol 1994 Oct;68(10):6270-9.
              18. Sellon DC, Fuller FJ, McGuire TC. The immunopathogenesis of equine infectious anemia virus. Virus Res 1994 May;32(2):111-38.
                doi: 10.1016/0168-1702(94)90038-8pubmed: 8067050google scholar: lookup
              19. Sellon DC, Perry ST, Coggins L, Fuller FJ. Wild-type equine infectious anemia virus replicates in vivo predominantly in tissue macrophages, not in peripheral blood monocytes. J Virol 1992 Oct;66(10):5906-13.
              20. Perry ST, Flaherty MT, Kelley MJ, Clabough DL, Tronick SR, Coggins L, Whetter L, Lengel CR, Fuller F. The surface envelope protein gene region of equine infectious anemia virus is not an important determinant of tropism in vitro. J Virol 1992 Jul;66(7):4085-97.
              21. Zhang Z, Guo K, Chu X, Liu M, Du C, Hu Z, Wang X. Development and evaluation of a test strip for the rapid detection of antibody against equine infectious anemia virus. Appl Microbiol Biotechnol 2024 Dec;108(1):85.
                doi: 10.1007/s00253-023-12980-9pubmed: 38189948google scholar: lookup