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Blood, 1 August 2004, Vol. 104, No. 3, pp. 687-695.
Prepublished online as a Blood First Edition Paper on April 13, 2004; DOI 10.1182/blood-2003-12-4344.
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Submitted December 19, 2003
Accepted March 24, 2004
Differential Outcomes of Human Cytomegalovirus Infection in Primitive Hematopoietic Subpopulations
Felicia Goodrum, Craig T Jordan, Scott S Terhune, Kevin High, and Thomas Shenk*
Department of Molecular Biology, Princeton University, Princeton, NJ, USA
Department of Medicine, University of Rochester School of Medicine, Rochester, NY, USA
Department of Infectious Disease, Wake Forest University School of Medicine, Winston-Salem, NC, USA
* Corresponding author; email: tshenk{at}molbio.princeton.edu.
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 subpopulations infected within the heterogeneous CD34+ compartment. We compared HCMV infection in well-defined CD34+ 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 postinfection. Importantly, viral replication could be reactivated by co-culture 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.
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