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Regulation of the viral life cycle by murine gammaherpesvirus 68 microRNAs

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Abstract

γ-Herpesviruses (γHV) such as Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus are important human pathogens involved in lymphoproliferation and tumorigenesis. Murine gammaherpesvirus 68 (MHV-68, γHV-68) is an effective model for the study of γHV pathogenesis and host-virus interaction because it is closely related to human γHV. Similarly to human γHV, MHV-68 encodes 15 microRNAs (miRNAs). Although their functions remain unknown, they are thought to regulate the viral life cycle or host-virus interactions, similarly to other human γHV. Herein, we established stable cell lines expressing MHV-68 miRNAs and investigated the role of MHV-68 miRNAs in the regulation of viral life cycle. We found that mghv-miR-M1-1, -3, -5, -7, -8, -9, -10, -11, -13, and -15 repressed MHV-68 lytic replication by down-regulating expression of the replication and transcription activator (RTA) gene, whereas mghv-miR-M1-2, -4, -6, and -12 induced lytic replication by up-regulating RTA. We confirmed that the decrease in viral replication caused by mghv-miR-M1-1 was abolished by inhibition of miRNA expression via miRNA inhibitor treatment. In addition, we observed that mghv-miR-M1-1 down-regulated c-Jun indirectly and decreased cytokine production, suggesting that mghv-miR-M1-1 may inhibit MHV-68 lytic replication by inhibiting the activator protein 1 (AP-1) signaling pathway.

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Acknowledgements

This work was supported by the National Research Foundation (NRF) funded by the Korean Government Ministry of Education, Science and Technology (MEST) [NRF-2010-0005856 to H.M.].

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Authors and Affiliations

  1. College of Pharmacy, Chung-Ang University, Seoul, 06974, Korea

    Soowon Kang, Chanoh Jeon, Kyungtaek Im & Hyeyoung Min

  2. Virus-Host Interactions Laboratory, Division of Biotechnology, Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Korea

    Moon Jung Song

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Kang, S., Jeon, C., Im, K. et al. Regulation of the viral life cycle by murine gammaherpesvirus 68 microRNAs. Arch Virol 162, 657–667 (2017). https://doi.org/10.1007/s00705-016-3150-y

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