title: miR-190 is upregulated in Epstein-Barr Virus type I latency and modulates cellular mRNAs involved in cell survival and viral reactivation.
abstract: Epstein-Barr Virus (EBV) is a prevalent human pathogen infecting over 90% of the population. Much of the success of the virus is attributed to its ability to maintain latency. The detailed mechanisms underlying the establishment and maintenance of EBV latency remain poorly understood. A microRNA profiling study revealed differential expression of many cellular miRNAs between types I and III latency cells, suggesting cellular miRNAs may play roles in regulating EBV latency. mir-190 is the most differentially up-regulated miRNA in type I latency cells as compared with type III latency cells and the up-regulation appears to be attributed to EBER RNAs that express in higher levels in type I latency cells than type III cells. With the aide of a lentiviral overexpression system and microarray analysis, several cellular mRNAs are identified as potential targets of mir-190. By targeting TP53INP1, miR-190 enhances cell survival by preventing apoptosis and relieving G0/G1 cell cycle arrest. Additionally, miR-190 down-regulates NR4A3, a cellular immediate-early gene for EBV reactivation, and inhibits the expression of the viral immediate-early gene bzlf1 and viral lytic DNA replication. Taken together, our data revealed a mechanism that EBV utilizes a cellular microRNA to promote host cell survival and prevent virus from entering lytic life cycle for latency maintenance.
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, 240 S. 40th Street, Philadelphia, PA 19104, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Cramer
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, 240 S. 40th Street, Philadelphia, PA 19104, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Institute of Human Virology, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, 240 S. 40th Street, Philadelphia, PA 19104, USA. Electronic address: yuan2@pobox.upenn.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D002460:Cell Line; D002470:Cell Survival; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014775:Virus Activation; D017735:Virus Latency
chemical_list: C576613:MIRN190 microRNA, human; D035683:MicroRNAs
keywords: EBER RNAs; EBV; Latency; NR4A3; TP53INP1; Viral reactivation; miR-190; miRNA