Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Int J Hematol. 2010 May;91(4):620-9. doi: 10.1007/s12185-010-0560-6. Epub 2010 Apr 8.
Human cytomegalovirus (HCMV) infection is usually implicated in thrombocytopenia occurring in newborns and immunocompromised patients. However, the underlying mechanisms remain elusive. This study was conducted to investigate the effects of HCMV infection on the viability of megakaryocytic CHRF-288-11 cells and the underlying mechanisms involved. RT-PCR for determining mRNA expression of HCMV immediate early gene 1 and Western blot for measuring protein expression of late HCMV gene pp65 showed that CHRF-288-11 cells were susceptible to HCMV infection. HCMV infection reduced the viability of CHRF-288-11 cells via apoptosis in a dose- and time-dependent manner. Both caspase 3 and c-Jun terminal kinase (JNK) signaling pathway were activated in the HCMV-treated CHRF-288-11 cells. z-DEVD-fmk (a caspase inhibitor) and SP600125 (a JNK inhibitor) significantly prevented the death of CHRF-288-11 cells induced by HCMV, respectively. Furthermore, inhibition of JNK activity could reduce the formation of active caspase 3 induced by HCMV. Interestingly, the co-application of antivirus drug ganciclovir and SP600125 synergistically prevented the death of CHRF-288-11 cells induced by HCMV. Collectively, these findings suggest that HCMV infection may induce the caspase-dependent apoptosis of megakaryocytic CHRF-288-11 cells by the activation of JNK signaling pathway.
人巨细胞病毒（HCMV）感染通常与新生儿和免疫功能低下患者的血小板减少症有关。然而，其潜在机制仍不清楚。本研究旨在探讨 HCMV 感染对巨核细胞 CHRF-288-11 细胞活力的影响及其相关机制。通过 RT-PCR 确定 HCMV 早期基因 1 的 mRNA 表达，通过 Western blot 测量晚期 HCMV 基因 pp65 的蛋白表达，结果显示 CHRF-288-11 细胞易受 HCMV 感染。HCMV 感染以剂量和时间依赖的方式通过凋亡降低 CHRF-288-11 细胞的活力。HCMV 处理的 CHRF-288-11 细胞中均激活了 caspase 3 和 c-Jun 末端激酶（JNK）信号通路。z-DEVD-fmk（一种 caspase 抑制剂）和 SP600125（一种 JNK 抑制剂）分别显著阻止了 HCMV 诱导的 CHRF-288-11 细胞死亡。此外，抑制 JNK 活性可减少 HCMV 诱导的活性 caspase 3 的形成。有趣的是，抗病毒药物更昔洛韦和 SP600125 的联合应用协同阻止了 HCMV 诱导的 CHRF-288-11 细胞死亡。总之，这些发现表明 HCMV 感染可能通过激活 JNK 信号通路诱导巨核细胞 CHRF-288-11 细胞的 caspase 依赖性凋亡。
