KSHV/HHV-8 infection of human hematopoietic progenitor (CD34+) cells: persistence of infection during hematopoiesis in vitro and in vivo.
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.
Department of Microbiology and Immunology, State University New York (SUNY) Upstate Medical University, Syracuse, NY, USA.
William
W
Wu
Jeffrey
J
Vieira
Nancy
N
Fiore
Prabal
P
Banerjee
Michelle
M
Sieburg
Rosemary
R
Rochford
William
W
Harrington
Gerold
G
Feuer
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D015967:Gene Expression Regulation, Viral; D006412:Hematopoietic Stem Cells / Q000821:virology*; D006566:Herpesviridae Infections / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014779:Virus Replication
D018952:Antigens, CD34