title: Regulation of the viral life cycle by murine gammaherpesvirus 68 microRNAs.
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.
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, 06974, Korea.
authors.forename: Soowon
authors.initials: S
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, 06974, Korea.
authors.forename: Chanoh
authors.initials: C
authors.lastname: Jeon
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, 06974, Korea.
authors.forename: Kyungtaek
authors.initials: K
authors.lastname: Im
authors.affiliation: Virus-Host Interactions Laboratory, Division of Biotechnology, Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Korea. moonsong@korea.ac.kr.
authors.forename: Moon Jung
authors.initials: MJ
authors.lastname: Song
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, 06974, Korea. hymin@cau.ac.kr.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Min
mesh_terms: D000818:Animals; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000662:veterinary* / Q000821:virology; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D018144:Rhadinovirus / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D012376:Rodent Diseases / Q000821:virology*; D012377:Rodentia; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral