HCMV infection of humanized mice after transplantation of G-CSF-mobilized peripheral blood stem cells from HCMV-seropositive donors

Biol Blood Marrow Transplant. 2014 Jan;20(1):132-5. doi: 10.1016/j.bbmt.2013.10.019. Epub 2013 Oct 23.

Abstract

Human cytomegalovirus (HCMV) infection, including primary infection resulting from transmission from a seropositive donor to a seronegative recipient (D(+)/R(-)), remains a significant problem in the setting of peripheral blood stem cell transplantation (PBSCT). The lack of a suitable animal model for studying HCMV transmission after PBSCT is a major barrier to understanding this process and, consequently, developing novel interventions to prevent HCMV infection. Our previous work demonstrated that human CD34(+) progenitor cell-engrafted NOD-scid IL2Rγc(null) (NSG) mice support latent HCMV infection after direct inoculation and reactivation after treatment with granulocyte colony-stimulating factor. To more accurately recapitulate HCMV infection in the D(+)/R(-) PBSCT setting, granulocyte colony-stimulating factor-mobilized peripheral blood stem cells from seropositive donors were used to engraft NSG mice. All recipient mice demonstrated evidence of HCMV infection in liver, spleen, and bone marrow. These findings validate the NSG mouse model for studying HCMV transmission during PBSCT.

Keywords: Cytomegalovirus; Latency; NSG mouse model; Stem cell transplantation; Transmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Bone Marrow / virology
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • Liver / immunology
  • Liver / pathology
  • Liver / virology
  • Mice
  • Mice, Transgenic
  • Peripheral Blood Stem Cell Transplantation*
  • Spleen / immunology
  • Spleen / pathology
  • Spleen / virology
  • Transplantation, Heterologous
  • Viral Load
  • Virus Activation
  • Virus Replication

Substances

  • Granulocyte Colony-Stimulating Factor