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ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Virology
Volume 15 - 2024 |
doi: 10.3389/fmicb.2024.1463335
Cytomegalovirus Results in Poor Graft Function via Bone Marrow-Derived Endothelial Progenitor Cells
Provisionally accepted- 1 Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
- 2 Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
Poor graft function (PGF), characterized by myelosuppression, represents a significant challenge following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with human cytomegalovirus (HCMV) being established as a risk factor for PGF. However, the underlying mechanism remains unclear. Bone marrow endothelial progenitor cells (BM-EPCs) play an important role in supporting hematopoiesis and their dysfunction contributes to PGF development. We aim to explore the effects of CMV on BM-EPCs and its underlying mechanism. We investigated the compromised functionality of EPCs derived from individuals diagnosed with HCMV viremia accompanied by PGF, as well as after infected by HCMV AD 169 strain in vitro, characterized by decreased cell proliferation, tube formation, migration and hematopoietic support, and increased apoptosis and secretion of TGF-β1. We demonstrated that HCMV-induced TGF-β1 secretion by BM-EPCs played a dominant role in hematopoiesis suppression in vitro experiment. Moreover, HCMV down-regulates Vitamin D receptor (VDR) and subsequently activates p38 MAPK pathway to promote TGF-β1 secretion by BM-EPCs. In conclusion, HCMV could infect BM-EPCs and lead to their dysfunction. The secretion of TGF-β1 by BM-EPCs is enhanced by CMV through the activation of p38 MAPK via a VDR-dependent mechanism, ultimately leading to compromised support for hematopoietic progenitors by BM EPCs, which may significantly contribute to the pathogenesis of PGF following allo-HSCT and provide innovative therapeutic strategies targeting PGF.
Keywords: poor graft function, Human Cytomegalovirus, endothelial progenitor cells, Transforming Growth Factor beta, vitamin D receptor
Received: 11 Jul 2024; Accepted: 09 Sep 2024.
Copyright: © 2024 Lv, Zhou, Zhao, Xuan, Huang, FAN, Chang, Yi, Jin, Liang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hua Jin, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China
Yang Liang, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
Qifa Liu, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
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