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

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

Morgan Hakki  1 , Devorah C Goldman  2 , Daniel N Streblow  3 , Kimberly L Hamlin  2 , Craig N Krekylwich  3 , William H Fleming  2 , Jay A Nelson  4
Affiliations

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

Morgan Hakki et al. Biol Blood Marrow Transplant. 2014 Jan.

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.

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Conflict of interest statement

Conflict-of-interest disclosure: the authors declare no competing financial interests

Figures

Figure 1
Figure 1. Engraftment of NSG mice after transplantation of G-CSF mobilized PBSCs
(A) Representative donor lineage analysis in xenografts. Flow cytometry of splenocytes from a mouse transplanted with PBSCs from donor 2 is shown. (B-D) Peripheral blood (B), bone marrow (C), and splenocytes (D) from mice transplanted with PBSCs from donors 2, 3, and 4 were analyzed at the time of tissue harvest for engraftment of human cell populations. Donor 1 human CD45+ engraftment was <0.5% in all mice.
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