Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model

M. Shane Smith, Devorah Goldman, Alexis S. Bailey, Dana L. Pfaffle, Craig N. Kreklywich, Doran B. Spencer, Florence A. Othieno, Daniel Streblow, J. Victor Garcia, William Fleming, Jay Nelson

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Human cytomegalovirus (HCMV) is a significant cause of morbidity and mortality in organ transplant recipients. The use of granulocyte-colony stimulating factor (G-CSF)-mobilized stem cells from HCMV seropositive donors is suggested to double the risk of late-onset HCMV disease and chronic graft-versus-host disease in recipients when compared to conventional bone marrow transplantation with HCMV seropositive donors, although the etiology of the increased risk is unknown. To understand mechanisms of HCMV transmission in patients receiving G-CSF-mobilized blood products, we generated a NOD-scid IL2Rγcnull-humanized mouse model in which HCMV establishes latent infection in human hematopoietic cells. In this model, G-CSF induces the reactivation of latent HCMV in monocytes/macrophages that have migrated into organ tissues. In addition to establishing a humanized mouse model for systemic and latent HCMV infection, these results suggest that the use of G-CSF mobilized blood products from seropositive donors pose an elevated risk for HCMV transmission to recipients.

Original languageEnglish (US)
Pages (from-to)284-291
Number of pages8
JournalCell Host and Microbe
Volume8
Issue number3
DOIs
Publication statusPublished - Sep 16 2010

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ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

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