Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model.
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 IL2Rγ(c)(null)-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.
Smith
M Shane
MS
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA.
Goldman
Devorah C
DC
Bailey
Alexis S
AS
Pfaffle
Dana L
DL
Kreklywich
Craig N
CN
Spencer
Doran B
DB
Othieno
Florence A
FA
Streblow
Daniel N
DN
Garcia
J Victor
JV
Fleming
William H
WH
Nelson
Jay A
JA
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000097:blood; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000821:virology; D006801:Humans; D008264:Macrophages / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000821:virology; D014775:Virus Activation; D017735:Virus Latency
D018952:Antigens, CD34; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor