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HCMV modulates c‐Mpl/IEX‐1 pathway‐mediated megakaryo/thrombopoiesis via PDGFRα and αvβ3 receptors after allo‐HSCT
Author(s) -
Feng FeiEr,
Zhang GaoChao,
Liu FengQi,
He Yun,
Zhu XiaoLu,
Liu Xiao,
Wang Yu,
Wang JingZhi,
Fu HaiXia,
Chen YuHong,
Han Wei,
Chang YingJun,
Xu LanPing,
Liu KaiYan,
Huang XiaoJun,
Zhang XiaoHui
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30335
Subject(s) - thrombopoiesis , human cytomegalovirus , megakaryocyte , platelet , receptor , cancer research , apoptosis , virology , biology , immunology , virus , medicine , haematopoiesis , microbiology and biotechnology , stem cell , biochemistry
Thrombocytopenia is a common complication of human cytomegalovirus (HCMV) infection in immunocompromised hosts, which contributes to poor prognosis even in patients receiving antiviral treatment. Here, we investigated the megakaryo/thrombopoiesis process, including the involvement of the c‐Mpl/IEX‐1 pathway, after HCMV infection, identified receptors mediating the interaction between megakaryocytes (MKs) and HCMV, and explored novel therapeutic targets. Our data shows that HCMV directly infects megakaryocytes in patients with HCMV DNAemia and influences megakaryopoiesis via the c‐Mpl/IEX‐1 pathway throughout megakaryocyte maturation, apoptosis, and platelet generation in vivo and in vitro. After treatment with inhibitors of PDGFRα and αvβ3, the HCMV infection rate in MKs was significantly reduced, suggesting that IMC‐3G3 and anti‐αvβ3 are potential therapeutic alternatives for viral infection. In summary, our study proposes a possible mechanism and potential treatments for thrombocytopenia caused by HCMV infection and other viral diseases associated with abnormal hemostasis.