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Human cytomegalovirus induces caspase-dependent apoptosis of megakaryocytic CHRF-288-11 cells by activating the JNK pathway

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Abstract

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.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (30872219), Natural Science Foundation of Guangdong Province (6300658 and 07001505), Research Grants Council of Hong Kong (PolyU660807, 560909; N_PolyU61807 and AoE/B15/01) and Hong Kong PolyU (G-YX96, G-U439). The authors sincerely thank Dr. Yijun Huang for his kind assistance in the flow cytometry assay and Professor Mingtao Li for kindly providing materials used in the experiments.

Conflict of interest statement

The authors declare that there is no conflict of interest including any financial, personal or other relationships with other people or organizations.

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Authors and Affiliations

  1. Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China

    Juan Dou, Xiaofeng Li, Yun Cai, Hong Chen, Shunye Zhu, Qingwen Wang & Xiaobing Zou

  2. Department of Biochemistry and Molecular Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China

    Yuping Mei

  3. Department of Infectious Diseases, The First Hospital of Xi’an JiaoTong University, Xi’an, 710061, China

    Qian Yang

  4. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong

    Wenming Li & Yifan Han

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  1. Juan Dou
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Correspondence to Juan Dou.

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Dou, J., Li, X., Cai, Y. et al. Human cytomegalovirus induces caspase-dependent apoptosis of megakaryocytic CHRF-288-11 cells by activating the JNK pathway. Int J Hematol 91, 620–629 (2010). https://doi.org/10.1007/s12185-010-0560-6

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  • DOI: https://doi.org/10.1007/s12185-010-0560-6

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