Human Cytomegalovirus Infection Suppresses CD34+ Progenitor Cell Engraftment in Humanized Mice

被引:6
作者
Crawford, Lindsey B. [1 ]
Tempel, Rebecca [1 ]
Streblow, Daniel N. [1 ]
Yurochko, Andrew D. [2 ]
Goodrum, Felicia D. [3 ]
Nelson, Jay A. [1 ]
Caposio, Patrizia [1 ]
机构
[1] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA
[2] Louisiana State Univ, Dept Microbiol & Immunol, Hlth Sci Ctr, Shreveport, LA 71130 USA
[3] Univ Arizona, BIO5 Inst, Dept Immunobiol, Tucson, AZ 85719 USA
基金
美国国家卫生研究院;
关键词
human cytomegalovirus; progenitor cell; hematopoietic stem cell transplant; myelosuppression; hematopoiesis; humanized mice; CORD BLOOD TRANSPLANTATION; BONE-MARROW; SINGLE-CENTER; LATENCY; GRAFT;
D O I
10.3390/microorganisms8040525
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human cytomegalovirus (HCMV) infection is a serious complication in hematopoietic stem cell transplant (HSCT) recipients due to virus-induced myelosuppression and impairment of stem cell engraftment. Despite the clear clinical link between myelosuppression and HCMV infection, little is known about the mechanism(s) by which the virus inhibits normal hematopoiesis because of the strict species specificity and the lack of surrogate animal models. In this study, we developed a novel humanized mouse model system that recapitulates the HCMV-mediated engraftment failure after hematopoietic cell transplantation. We observed significant alterations in the hematopoietic populations in peripheral lymphoid tissues following engraftment of a subset of HCMV+ CD34(+) hematopoietic progenitor cells (HPCs) within the transplant, suggesting that a small proportion of HCMV-infected CD34(+) HPCs can profoundly affect HPC differentiation in the bone marrow microenvironment. This model will be instrumental to gain insight into the fundamental mechanisms of HCMV myelosuppression after HSCT and provides a platform to assess novel treatment strategies.
引用
收藏
页数:9
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