title: KSHV miRNAs decrease expression of lytic genes in latently infected PEL and endothelial cells by targeting host transcription factors.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) microRNAs are encoded in the latency-associated region. Knockdown of KSHV miR-K12-3 and miR-K12-11 increased expression of lytic genes in BC-3 cells, and increased virus production from latently infected BCBL-1 cells. Furthermore, iSLK cells infected with miR-K12-3 and miR-K12-11 deletion mutant viruses displayed increased spontaneous reactivation and were more sensitive to inducers of reactivation than cells infected with wild type KSHV. Predicted binding sites for miR-K12-3 and miR-K12-11 were found in the 3'UTRs of the cellular transcription factors MYB, Ets-1, and C/EBPα, which activate RTA, the KSHV replication and transcription activator. Targeting of MYB by miR-K12-11 was confirmed by cloning the MYB 3'UTR downstream from the luciferase reporter. Knockdown of miR‑K12-11 resulted in increased levels of MYB transcript, and knockdown of miR-K12-3 increased both C/EBPα and Ets-1 transcripts. Thus, miR-K12-11 and miR-K12-3 contribute to maintenance of latency by decreasing RTA expression indirectly, presumably via down-regulation of MYB, C/EBPα and Ets-1, and possibly other host transcription factors.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. karliebonstaff@gmail.com.
authors.forename: Karlie
authors.initials: K
authors.lastname: Plaisance-Bonstaff
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. hschoi@ufl.edu.
authors.forename: Hong Seok
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. tbeals@ufl.edu.
authors.forename: Tyler
authors.initials: T
authors.lastname: Beals
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. brian.krueger@duke.edu.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Krueger
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. iboss2022@gmail.com.
authors.forename: Isaac W
authors.initials: IW
authors.lastname: Boss
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. lagay@ufl.edu.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Gay
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. irina25@me.com.
authors.forename: Irina
authors.initials: I
authors.lastname: Haecker
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. Jianhong.Hu@bcm.edu.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. rrenne@ufl.edu.
authors.forename: Rolf
authors.initials: R
authors.lastname: Renne
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D042783:Endothelial Cells / Q000821:virology; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization; D017735:Virus Latency
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral; D011991:Receptors, Virus; D014157:Transcription Factors; D014764:Viral Proteins