Parvovirus B19 capsid protein VP2 inhibits hematopoiesis in vitro and in vivo: implications for therapeutic use.
OBJECTIVE
To evaluate the capacity of parvovirus B19 capsid protein VP2 to inhibit hematopoiesis in vitro and in vivo. If effective, a VP2-derived construct may have therapeutic and prophylactic utility in diseases associated to overproduction of hematopoietic cells.


METHODS
The effect on hematopoiesis in vitro of recombinant VP2, intact and enzymatically fragmented, was evaluated in a colony formation assay, using cells from fetal liver and macaque bone marrow. VP2 was also administered intravenously in macaques and hematological parameters as well as the ex vivo colony formation were assayed during a follow-up period of 33 days.


RESULTS
VP2 inhibited BFU-E colony formation by about 55%. CFU-GM and CFU-GEMM colony formation was also affected. Fragmented VP2 retained the inhibitory effect. The ex vivo colony-forming capacity of macaque bone marrow cells was lower in animals that received VP2 injections, and a drop in hematocrit values was noted in one animal.


CONCLUSIONS
VP2 has an inhibitory effect on hematopoiesis in vitro and in vivo. An active region within VP2 is implied, which would be a strong candidate for use as a medicament in diseases such as polycytemia vera.
Norbeck
Oscar
O
Division of Clinical Virology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. oscar.norbeck@labmed.ki.se
Tolfvenstam
Thomas
T
Shields
Laurence E
LE
Westgren
Magnus
M
Broliden
Kristina
K
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D036022:Capsid Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000166:cytology; D008251:Macaca; D010446:Peptide Fragments / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism
D036022:Capsid Proteins; D010446:Peptide Fragments; C095548:capsid protein VP2, parvovirus B19; D010447:Peptide Hydrolases