Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice

Michael L. Freeman, Claire E. Burkum, Kathleen G. Lanzer, Alan D. Roberts, Mykola Pinkevych, Asako Itakura, Lawrence W. Kummer, Frank M. Szaba, Miles P. Davenport, Owen McCarty, David L. Woodland, Stephen T. Smiley, Marcia A. Blackman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Human herpesviruses establish lifelong latency. Viral recrudescence can lead to the development of cancers, immunoproliferative disorders, transplantation complications, and thrombocytopenia. Although platelet-specific autoantibodies have been reported in patients infected with the Epstein-Barr virus (EBV), the mechanisms by which thrombocytopenia is induced remain unclear, as do the relative contributions of lytic viral replication and latent viral gene expression. The human gammaherpesviruses are tightly restricted in their ability to infect other mammals, so they are difficult to study in live animal models. Here we show that infection of mice with murine gammaherpesvirus-68 (γHV68), a rodent-specific pathogen closely related to EBV, induces the production of platelet-binding antibodies and causes thrombocytopenia. Infection of antibody-deficient mice does not lead to thrombocytopenia, indicating the platelet decrease is mediated by antibody. Additionally, infection with a latency-null recombinant γHV68 does not induce thrombocytopenia, suggesting factors associated with viral latency drive the infection-induced antibody-mediated thrombocytopenia. These studies describe an important animal model of gammaherpesvirus-induced autoimmune thrombocytopenia and demonstrate that this pathology is mediated by antibody and dependent on viral latency. This model will allow studies of the underlying mechanisms of disease progression and the testing of therapeutic strategies for the alleviation of virus-induced thrombocytopenia.

Original languageEnglish (US)
Pages (from-to)71-79
Number of pages9
JournalJournal of Autoimmunity
Volume42
DOIs
StatePublished - May 2013

Fingerprint

Thrombocytopenia
Antibodies
Virus Latency
Blood Platelets
Infection
Human Herpesvirus 4
Immunoproliferative Disorders
Animal Models
Idiopathic Thrombocytopenic Purpura
Viral Genes
Herpesviridae
Autoantibodies
Disease Progression
Mammals
Rodentia
Transplantation
Pathology
Viruses
Gene Expression
Recurrence

Keywords

  • Gammaherpesvirus
  • Thrombocytopenia
  • Viral latency

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Freeman, M. L., Burkum, C. E., Lanzer, K. G., Roberts, A. D., Pinkevych, M., Itakura, A., ... Blackman, M. A. (2013). Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice. Journal of Autoimmunity, 42, 71-79. https://doi.org/10.1016/j.jaut.2012.11.005

Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice. / Freeman, Michael L.; Burkum, Claire E.; Lanzer, Kathleen G.; Roberts, Alan D.; Pinkevych, Mykola; Itakura, Asako; Kummer, Lawrence W.; Szaba, Frank M.; Davenport, Miles P.; McCarty, Owen; Woodland, David L.; Smiley, Stephen T.; Blackman, Marcia A.

In: Journal of Autoimmunity, Vol. 42, 05.2013, p. 71-79.

Research output: Contribution to journalArticle

Freeman, ML, Burkum, CE, Lanzer, KG, Roberts, AD, Pinkevych, M, Itakura, A, Kummer, LW, Szaba, FM, Davenport, MP, McCarty, O, Woodland, DL, Smiley, ST & Blackman, MA 2013, 'Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice', Journal of Autoimmunity, vol. 42, pp. 71-79. https://doi.org/10.1016/j.jaut.2012.11.005
Freeman ML, Burkum CE, Lanzer KG, Roberts AD, Pinkevych M, Itakura A et al. Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice. Journal of Autoimmunity. 2013 May;42:71-79. https://doi.org/10.1016/j.jaut.2012.11.005
Freeman, Michael L. ; Burkum, Claire E. ; Lanzer, Kathleen G. ; Roberts, Alan D. ; Pinkevych, Mykola ; Itakura, Asako ; Kummer, Lawrence W. ; Szaba, Frank M. ; Davenport, Miles P. ; McCarty, Owen ; Woodland, David L. ; Smiley, Stephen T. ; Blackman, Marcia A. / Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice. In: Journal of Autoimmunity. 2013 ; Vol. 42. pp. 71-79.
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