title: HCMV infection of humanized mice after transplantation of G-CSF-mobilized peripheral blood stem cells from HCMV-seropositive donors.
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.
authors.affiliation: Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon.
authors.forename: Morgan
authors.initials: M
authors.lastname: Hakki
authors.affiliation: Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon.
authors.forename: Devorah C
authors.initials: DC
authors.lastname: Goldman
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Streblow
authors.affiliation: Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Hamlin
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Krekylwich
authors.affiliation: Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon.
authors.forename: William H
authors.initials: WH
authors.lastname: Fleming
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon. Electronic address: nelsonj@ohsu.edu.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Nelson
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology / Q000821:virology; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D036102:Peripheral Blood Stem Cell Transplantation; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology; D014183:Transplantation, Heterologous; D019562:Viral Load; D014775:Virus Activation; D014779:Virus Replication
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: Cytomegalovirus; Latency; NSG mouse model; Stem cell transplantation; Transmission