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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.
HEMATOPOIESIS KSHV/HHV-8 infection of human hematopoietic progenitor (CD34+) cells: persistence of infection during hematopoiesis in vitro and in vivoFrom the Department of Microbiology and Immunology, State University New York (SUNY) Upstate Medical University, Syracuse, NY; the Department of Laboratory Medicine, University of Washington, and Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA; and the Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL.
The cellular reservoir for Kaposi sarcoma-associated herpesvirus (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 differentiated in vitro. rKSHV.219 is a recombinant KSHV construct that expresses green fluorescent protein from a cellular promoter active during latency and red fluorescent protein 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. (Blood. 2006;108:141-151)
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