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Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations. Blood 2004 Aug 01;104(3):687-95

Date

04/20/2004

Pubmed ID

15090458

DOI

10.1182/blood-2003-12-4344

Scopus ID

2-s2.0-3242780176   115 Citations

Abstract

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.

Author List

Goodrum F, Jordan CT, Terhune SS, High K, Shenk T

Author

Scott Terhune PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

ADP-ribosyl Cyclase
ADP-ribosyl Cyclase 1
Antigens, CD
Antigens, CD34
Bone Marrow Cells
Cell Culture Techniques
Cytomegalovirus
Cytomegalovirus Infections
Flow Cytometry
Hematopoiesis
Hematopoietic Stem Cells
Humans
Kinetics
Membrane Glycoproteins
Polymerase Chain Reaction
Time Factors
Tissue Donors
Virus Replication