Parvovirus B19 Infection in Human Bone Marrow Mesenchymal Stem Cells Affects Gene Expression of IL-6 and TNF-α and also Affects Hematopoietic Stem Cells Differentiation
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Parvovirus B19 (B19V) has been known to induce transient erythroid aplasia, cytopenia and aplastic anemia. This virus persists in bone marrow mesenchymal stem cells (HBMSCs) of some immunocompetent individuals several years after primary infection. In B19V infected erythroid progenitor cells, the virus induces transactivation of Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) gene expression. Due the critical role of HBMSCs in bone marrow niche and inhibitory effect of inflammatory cytokines on hematopoiesis, the aim of this study was to investigate the effect of B19V on IL-6 and TNF-α gene expression intransfected cells. In addition we assessed the clonogenicity potential of cord blood CD34+ stem cells that were co-cultured with infected cells. After 24 h of transfection, quantitative mRNA expression of IL-6 and TNF-α was evaluated and human cord blood CD34+ HSC were cultured with the transfected cells. At the end of 7 days of culture, HSCs colony forming units (CFUs) assay was performed. Our findings demonstrated statistically significant (18.1 and 21.9 fold) increase of TNF-α and IL-6 gene expression respectively and decrease in burst forming unit-erythrocyte (BFU-E) and colony forming unit-erythrocyte (CFU-E) enumeration(p < 0.05). We concluded that, inducing inflammatory cytokines gene expression in B19V-infected HBMSCs might influence on bone marrow microenvironment and hematopoiesis.
KeywordsColony forming assay Hematopoietic stem cells Human bone marrow mesenchymal stem cells Inflammatory cytokines Parvovirus B19
Human bone marrow mesenchymal stem cells
Tumor necrosis factor-α
Nonstructural protein 1
Human herpes virus 6
Hepatitis A/C viruses
Human immunodeficiency virus
Fetal bovine serum
Dulbecco’s modified eagle’s medium
Colony forming unit-granulocyte/erythrocyte monocyte/megakaryocyte
Colony forming unit-granulocyte/monocyte
Colony forming unit-granulocyte
Colony forming unit-monocyte
Burst forming unit-erythrocyte
Colony forming unit-erythrocyte
Erythroid progenitor cells
The authors are thankful to Dr. Giorgio Gallinella, Department of Pharmacy and Biotechnology, S. Orsola-Malpighi Hospital - Microbiology, University of Bologna, Bologna, Italy for kind gifting pHI0-plasmid. The results described in this paper were part of a student thesis and was financially supported by Deputy of Research Affairs and Faculty of Medical Sciences at Tarbiat Modares University, Tehran, Iran.
AA and SK designed the experiments. MBF carried out the experiments, analyzed the data and wrote the manuscript.
This work was supported by a grant from Tarbiat Modares University of Medical Sciences (Grant Number IR.TUM.REC0.53934).
Compliance with Ethical Standards
Conflict of interest
The authors report no conflicts of interest in this work.
This study was approved by the local ethics committee of Tarbiat Modares University of Medical Sciences (Approval Number IR.TMU.REC0.1394.288).
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