title: Evolutionary conservation of primate lymphocryptovirus microRNA targets.
abstract: Epstein-Barr virus (EBV) and rhesus lymphocryptovirus (rLCV) are closely related gammaherpesviruses in the lymphocryptovirus subgroup that express viral microRNAs (miRNAs) during latent infection. In addition to many host mRNAs, EBV miRNAs are known to target latent viral transcripts, specifically those encoding LMP1, BHRF1, and EBNA2. The mRNA targets of rLCV miRNAs have not been investigated. Using luciferase reporter assays, photoactivatable cross-linking and immunoprecipitation (PAR-CLIP), and deep sequencing, we demonstrate that posttranscriptional regulation of LMP1 expression is a conserved function of lymphocryptovirus miRNAs. Furthermore, the mRNAs encoding the rLCV EBNA2 and BHRF1 homologs are regulated by miRNAs in rLCV-infected B cells. Homologous to sites in the EBV LMP1 and BHRF1 3'-untranslated regions (UTRs), we also identified evolutionarily conserved binding sites for the cellular miR-17/20/106 family in the LMP1 and BHRF1 3'UTRs of several primate LCVs. Finally, we investigated the functional consequences of LMP1 targeting by individual EBV BART miRNAs and show that select viral miRNAs play a role in the previously observed modulation of NF-κB activation.
authors.affiliation: Department of Molecular Genetics & Microbiology and Center for Virology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Skalsky
authors.forename: Dong
authors.initials: D
authors.lastname: Kang
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Linnstaedt
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Cullen
mesh_terms: D000818:Animals; D001483:Base Sequence; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D019143:Evolution, Molecular; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018143:Lymphocryptovirus / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008253:Macaca mulatta; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D018419:Primate Diseases / Q000821:virology*; D011323:Primates; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral; D014764:Viral Proteins