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Regulation of CCAAT/enhancer-binding protein (C/EBP) α in human-cytomegalovirus-infected fibroblasts

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Abstract

CCAAT/enhancer-binding protein (C/EBP) α, a member of the C/EBP family of transcription factors, is known to be involved in gene expression and DNA replication of human cytomegalovirus (HCMV). This study aimed to understand the regulation of endogenous C/EBPα during HCMV infection using an in vitro infection model. The expression and localization of C/EBPα were investigated in fibroblasts infected with HCMV. The overexpression of C/EBP homologous protein (CHOP), the endogenous inhibitor of C/EBP, was also employed to test the involvement of C/EBPα during HCMV infection. Our data showed that HCMV infection increases the expression of the full-length C/EBPα isoform (p42) especially during the late stage of infection at the transcriptional and post-translational levels. The increased p42 accumulated in the viral DNA replication compartment. p42 expression was not induced in cells treated with UV-irradiated virus or in cells infected with normal virus in the presence of ganciclovir. CHOP-mediated inhibition of C/EBP activity suppressed viral gene expression and DNA replication, which lowered the level of viral production. Together, our data suggest that HCMV-mediated C/EBPα regulation might play a beneficial role in the lytic cycle of HCMV.

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Acknowledgments

We greatly appreciate Jyhyun Ahn for critical reading of the manuscript. This research was supported by grants from 1) the Brain Research Center of the 21st Century Frontier Research Program (2012K001130) and 2 and 3) the Basic Science Research Programs through the National Research Foundation of Korea (NRF) (2012R1A1A2008018 and 2014R1A1A2055890, respectively) funded by the Ministry of Education.

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  1. Laboratory of Virology, School of Biological Sciences, Seoul National University, Seoul, 151-747, Korea

    Junsub Lee & Sunyoung Kim

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Correspondence to Sunyoung Kim.

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Lee, J., Kim, S. Regulation of CCAAT/enhancer-binding protein (C/EBP) α in human-cytomegalovirus-infected fibroblasts. Arch Virol 161, 1151–1158 (2016). https://doi.org/10.1007/s00705-016-2768-0

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