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

摘要

Human cytomegalovirus (HCMV) infection remains a significant problem in the setting of peripheral blood stem cell transplant (PBSCT), including primary infection resulting from transmission from a seropositive donor to a seronegative recipient (D+/R−). The lack of an animal model suitable for studying HCMV transmission after PBSCT is a major barrier in understanding this process and, consequently, the development of 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 G-CSF. To more accurately recapitulate HCMV infection in the D+/R− PBSCT setting, granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) from seropositive donors were used to engraft NSG mice. All recipient mice demonstrated evidence of HCMV infection in liver, spleen, and bone marrow. These observations validate the NSG mouse model as a means to study HCMV transmission during PBSCT.