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DCAF1 is involved in HCV replication through regulation of miR-122

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Abstract

Hepatitis C virus (HCV) is a worldwide threaten to human health with a high ratio of chronic infections. Recently, we found that Vpr-mediated regulation of HCV replication depends on the host protein DDB1-Cul4 associate factor 1 (DCAF1), implying that DCAF1 might be involved in the replication of HCV. In this study, we demonstrated that DCAF1 knockdown reduced HCV replication both in the infectious (JFH1) and replicon (Con1) systems. Further investigation showed a negative regulation of HCV internal ribosome entry site (IRES)-mediated translation by DCAF1. Considering the positive effects on the replication of the HCV replicon, we speculated that DCAF1 affected the balance between HCV RNA replication and protein translation. Since miR-122 is involved in the regulation of this balance, we investigated the influence of DCAF1 on miR-122 expression. By measuring the expression of miR-122, pre-miR-122 and its target CAT-1 mRNA, we found that miR-122 was downregulated following DCAF1 knockdown. Furthermore, overexpression of miR-122 rescued HCV replication impairment induced by DCAF1 knockdown. In conclusion, our study suggests that DCAF1 is involved in HCV replication through regulation of miR-122 and thus provides new insights into the interaction between HCV and the host cell.

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Acknowledgements

We would like to thank Dr. Takaji Wakita (National Institute of Infectious Diseases, Japan) for providing the JFH1 plasmid, and Dr. F.V. Chisari (The Scripps Research Institute, USA) for providing the Huh7.5.1 cells. We are grateful for technical support from the Core Facility and Technical Support, Wuhan Institute of Virology. This work was funded by the Key National Science and Technology Program in the 12th Five-Year Period (Grant2012ZX10001-006) and the Key Laboratory on Emerging Infectious Disease and Biosafety in Wuhan.

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Authors and Affiliations

  1. Research Group of HIV Molecular Epidemiology and Virology, Center for Molecular Virology, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, Hubei, People’s Republic of China

    Yanling Yan, Conghui Li, Binlian Sun & Rongge Yang

  2. University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China

    Yanling Yan & Conghui Li

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  1. Yanling Yan
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Correspondence to Binlian Sun or Rongge Yang.

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Yan, Y., Li, C., Sun, B. et al. DCAF1 is involved in HCV replication through regulation of miR-122. Arch Virol 163, 977–985 (2018). https://doi.org/10.1007/s00705-017-3691-8

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