Parvovirus B19 capsid protein VP2 inhibits hematopoiesis in vitro and in vivo: implications for therapeutic use
| Autor: | Magnus Westgren, Oscar Norbeck, Laurence E. Shields, Thomas Tolfvenstam, Kristina Broliden |
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| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
viruses Bone Marrow Cells Macaque law.invention Colony-Forming Units Assay Fetus In vivo law biology.animal Genetics medicine Animals Humans Molecular Biology Cells Cultured biology Dose-Response Relationship Drug Parvovirus virus diseases Cell Biology Hematology biochemical phenomena metabolism and nutrition biology.organism_classification Hematopoietic Stem Cells Molecular biology In vitro Peptide Fragments Hematopoiesis Haematopoiesis medicine.anatomical_structure Liver Recombinant DNA Macaca Capsid Proteins Bone marrow Ex vivo Peptide Hydrolases |
| Zdroj: | Experimental hematology. 32(11) |
| ISSN: | 0301-472X |
| Popis: | 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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