Recombinant parvovirus B19 empty capsids inhibit fetal hematopoietic colony formation in vitro.
Erythroid lineage cells are target cells for human parvovirus B19, and a natural infection often results in transient anemia. To determine whether recombinant B19 capsid proteins (VP1/VP2) also inhibit human hematopoietic progenitor growth, a model system was set up. The B19 capsids were inoculated into primary cultures of hematopoietic stem cells derived from human fetal liver, resulting in a 70-95% reduction of BFU-E (burst-forming unit erythroid cells) as compared with the medium control. A similar effect was seen in human hematopoietic stem cell cultures derived from cord blood and adult bone marrow. Preincubation of the B19 capsids with either a monoclonal antibody to the virus or with B19 IgG positive human sera reduced the inhibitory effect. Furthermore, the inhibitory effect could be reduced by preincubating the target cells with a monoclonal antibody to the cellular receptor for the virus, the P antigen. These findings thus show that the inhibition of colony formation of human hematopoietic stem cells can occur in the absence of parvovirus B19 nonstructural proteins. We speculate that B19 capsid could provide a possible strategy to downregulate indigenous hematopoiesis in fetal stem cell transplantations.
Lindton
B
B
Department of Obstetrics and Gynecology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
Tolfvenstam
T
T
Norbeck
O
O
Markling
L
L
Ringdén
O
O
Westgren
M
M
Broliden
K
K
D000328:Adult; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D002213:Capsid / Q000494:pharmacology*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005333:Fetus; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016732:Parvovirus B19, Human; D011247:Pregnancy