Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations.
The cellular reservoir for latent human cytomegalovirus (HCMV) in the hematopoietic compartment, and the mechanisms governing a latent infection and reactivation from latency are unknown. Previous work has demonstrated that HCMV infects CD34+ progenitors and expresses a limited subset of viral genes. The outcome of HCMV infection may depend on the cell subpopulations infected within the heterogeneous CD34+ compartment. We compared HCMV infection in well-defined CD34+ cell subpopulations. HCMV infection inhibited hematopoietic colony formation from CD34+/CD38- but not CD34+/c-kit+ cells. CD34+/CD38- cells transiently expressed a large subset of HCMV genes that were not expressed in CD34+/c-kit+ cells or cells expressing more mature cell surface phenotypes. Although viral genomes were present in infected cells, viral gene expression was undetectable by 10 days after infection. Importantly, viral replication could be reactivated by coculture with permissive fibroblasts only from the CD34+/CD38- population. Strikingly, a subpopulation of CD34+/CD38- cells expressing a stem cell phenotype (lineage-/Thy-1+) supported a productive HCMV infection. These studies demonstrate that the outcome of HCMV infection in the hematopoietic compartment is dependent on the nature of the cell subpopulations infected and that CD34+/CD38- cells support an HCMV infection with the hallmarks of latency.
Goodrum
Felicia
F
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Jordan
Craig T
CT
Terhune
Scott S
SS
High
Kevin
K
Shenk
Thomas
T
D036541:ADP-ribosyl Cyclase / Q000097:blood; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000097:blood*; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000821:virology*; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins; D016133:Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014019:Tissue Donors; D014779:Virus Replication
D015703:Antigens, CD; D018952:Antigens, CD34; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1