PMID- 24257599 OWN - NLM STAT- MEDLINE DCOM- 20140416 LR - 20211021 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 88 IP - 3 DP - 2014 Feb TI - Evolutionary conservation of primate lymphocryptovirus microRNA targets. PG - 1617-35 LID - 10.1128/JVI.02071-13 [doi] AB - 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-kappaB activation. FAU - Skalsky, Rebecca L AU - Skalsky RL AD - Department of Molecular Genetics & Microbiology and Center for Virology, Duke University Medical Center, Durham, North Carolina, USA. FAU - Kang, Dong AU - Kang D FAU - Linnstaedt, Sarah D AU - Linnstaedt SD FAU - Cullen, Bryan R AU - Cullen BR LA - eng GR - R01-AI067968/AI/NIAID NIH HHS/United States GR - R01 AI067968/AI/NIAID NIH HHS/United States GR - P30-AI064518/AI/NIAID NIH HHS/United States GR - T32 CA009111/CA/NCI NIH HHS/United States GR - P30 AI064518/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20131120 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (MicroRNAs) RN - 0 (RNA, Viral) RN - 0 (Viral Proteins) SB - IM MH - Animals MH - Base Sequence MH - Epstein-Barr Virus Infections/*virology MH - *Evolution, Molecular MH - *Gene Expression Regulation, Viral MH - Herpesvirus 4, Human/chemistry/classification/genetics/metabolism MH - Humans MH - Lymphocryptovirus/chemistry/classification/*genetics/metabolism MH - Macaca mulatta MH - MicroRNAs/chemistry/*genetics/metabolism MH - Molecular Sequence Data MH - Primate Diseases/*virology MH - Primates MH - RNA, Viral/chemistry/*genetics/metabolism MH - Sequence Alignment MH - Viral Proteins/*genetics/metabolism PMC - PMC3911612 EDAT- 2013/11/22 06:00 MHDA- 2014/04/17 06:00 PMCR- 2014/08/01 CRDT- 2013/11/22 06:00 PHST- 2013/11/22 06:00 [entrez] PHST- 2013/11/22 06:00 [pubmed] PHST- 2014/04/17 06:00 [medline] PHST- 2014/08/01 00:00 [pmc-release] AID - JVI.02071-13 [pii] AID - 02071-13 [pii] AID - 10.1128/JVI.02071-13 [doi] PST - ppublish SO - J Virol. 2014 Feb;88(3):1617-35. doi: 10.1128/JVI.02071-13. Epub 2013 Nov 20.