Viral opportunistic infections in Mauritian cynomolgus macaques undergoing allogeneic stem cell transplantation mirror human transplant infectious disease complications

Helen L. Wu, Whitney C. Weber, Christine Shriver-Munsch, Tonya Swanson, Mina Northrup, Heidi Price, Kimberly Armantrout, Mitchell Robertson-LeVay, Jason S. Reed, Katherine B. Bateman, Eisa Mahyari, Archana Thomas, Stephanie L. Junell, Theodore R. Hobbs, Lauren D. Martin, Rhonda MacAllister, Benjamin N. Bimber, Mark K. Slifka, Alfred W. Legasse, Cassandra MoatsMichael K. Axthelm, Jeremy Smedley, Anne D. Lewis, Lois Colgin, Gabrielle Meyers, Richard T. Maziarz, Benjamin J. Burwitz, Jeffrey J. Stanton, Jonah B. Sacha

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) and xenotransplantation are accompanied by viral reactivations and virus-associated complications resulting from immune deficiency. Here, in a Mauritian cynomolgus macaque model of fully MHC-matched allogeneic HSCT, we report reactivations of cynomolgus polyomavirus, lymphocryptovirus, and cytomegalovirus, macaque viruses analogous to HSCT-associated human counterparts BK virus, Epstein-Barr virus, and human cytomegalovirus. Viral replication in recipient macaques resulted in characteristic disease manifestations observed in HSCT patients, such as polyomavirus-associated hemorrhagic cystitis and tubulointerstitial nephritis or lymphocryptovirus-associated post-transplant lymphoproliferative disorder. However, in most cases, the reconstituted immune system, alone or in combination with short-term pharmacological intervention, exerted control over viral replication, suggesting engraftment of functional donor-derived immunity. Indeed, the donor-derived reconstituted immune systems of two long-term engrafted HSCT recipient macaques responded to live attenuated yellow fever 17D vaccine (YFV 17D) indistinguishably from untransplanted controls, mounting 17D-targeted neutralizing antibody responses and clearing YFV 17D within 14 days. Together, these data demonstrate that this macaque model of allogeneic HSCT recapitulates clinical situations of opportunistic viral infections in transplant patients and provides a pre-clinical model to test novel prophylactic and therapeutic modalities.

Original languageEnglish (US)
Article numbere12578
JournalXenotransplantation
Volume27
Issue number4
DOIs
StatePublished - Jul 1 2020

Keywords

  • Mauritian cynomolgus macaques
  • cytomegalovirus
  • hematopoietic stem cell transplantation
  • lymphocryptovirus
  • non-human primates
  • opportunistic infections
  • polyomavirus
  • transplant complications
  • yellow fever virus

ASJC Scopus subject areas

  • Immunology
  • Transplantation

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