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Blood, 1 July 2006, Vol. 108, No. 1, pp. 141-151.
Prepublished online as a Blood First Edition Paper on March 16, 2006; DOI 10.1182/blood-2005-04-1697.
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Submitted April 26, 2005
Accepted February 22, 2006
KSHV/HHV-8 infection of human hematopoietic progenitor (CD34+) cells: persistence of infection during hematopoiesis in vitro and in vivo
William Wu, Jeffrey Vieira, Nancy Fiore, Prabal Banerjee, Michelle Sieburg, Rosemary Rochford, William Harrington, Jr., and Gerold Feuer*
Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY, USA
Department of Laboratory Medicine, University of Washington, Seattle, WA, USA; Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA
* Corresponding author; email: feuerg{at}upstate.edu.
The cellular reservoir for KSHV infection in the hematopoietic compartment and mechanisms governing latent infection and reactivation remain undefined. To determine susceptibility of human CD34+ hematopoietic progenitor cells (HPCs) to infection with KSHV, purified HPCs were exposed to KSHV and cells were differentiated in vitro and in vivo. Clonogenic colony forming activity was significantly suppressed in KSHV-infected CD34+ cells and viral DNA was predominantly localized to granulocyte-macrophage colonies (CFU-GM) differentiated in vitro. rKSHV.219 is a recombinant KSHV construct which expresses GFP from a cellular promoter active during latency and RFP from a viral lytic promoter. Infection of CD34+ HPCs with rKSHV.219 showed similar patterns of infection, persistence and hematopoietic suppression in vitro in comparison with KSHV. rKSHV.219 infection was detected in human CD14+ and CD19+ cells recovered from NOD/SCID mouse bone marrow and spleen following reconstitution with rKSHV.219-infected CD34+ HPCs. These results suggest that rKSHV.219 establishes persistent infection in NOD/SCID mice and that virus may be disseminated following differentiation of infected HPCs into the B cell and monocyte lineages. CD34+ HPCs may be a reservoir for KSHV infection and may provide a continuous source of virally infected cells in vivo.

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