title: Changes in cellular microRNA expression induced by porcine circovirus type 2-encoded proteins.
abstract: Porcine circovirus type 2 (PCV2) is the primary causative agent of postweaning multisystemic wasting syndrome, which leads to serious economic losses in the pig industry worldwide. While the molecular basis of PCV2 replication and pathogenicity remains elusive, it is increasingly apparent that the microRNA (miRNA) pathway plays a key role in controlling virus-host interactions, in addition to a wide range of cellular processes. Here, we employed Solexa deep sequencing technology to determine which cellular miRNAs were differentially regulated after expression of each of three PCV2-encoded open reading frames (ORFs) in porcine kidney epithelial (PK15) cells. We identified 51 ORF1-regulated miRNAs, 74 ORF2-regulated miRNAs, and 32 ORF3-regulated miRNAs that differed in abundance compared to the control. Gene ontology analysis of the putative targets of these miRNAs identified transcriptional regulation as the most significantly enriched biological process, while KEGG pathway analysis revealed significant enrichment for several pathways including MAPK signaling, which is activated during PCV2 infection. Among the potential target genes of ORF-regulated miRNAs, two genes encoding proteins that are known to interact with PCV2-encoded proteins, zinc finger protein 265 (ZNF265) and regulator of G protein signaling 16 (RGS16), were selected for further analysis. We provide evidence that ZNF265 and RGS16 are direct targets of miR-139-5p and let-7e, respectively, which are both down-regulated by ORF2. Our data will initiate further studies to elucidate the roles of ORF-regulated cellular miRNAs in PCV2-host interactions.
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Korea. jsf7205@korea.ac.kr.
authors.forename: Jae-Sang
authors.initials: JS
authors.lastname: Hong
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Korea. knh1221@korea.ac.kr.
authors.forename: Nam-Hoon
authors.initials: NH
authors.lastname: Kim
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Korea. magical87@naver.com.
authors.forename: Chang-Yong
authors.initials: CY
authors.lastname: Choi
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Korea. tturr@hanmail.net.|Present address: Institut de Recherches Cliniques de Montréal, Montréal, Québec, H2W1R7, Canada. tturr@hanmail.net.
authors.forename: Jun-Seong
authors.initials: JS
authors.lastname: Lee
authors.affiliation: School of Integrative Engineering, Chung-Ang University, Seoul, 156-756, Korea. dokyunna@gmail.com.
authors.forename: Dokyun
authors.initials: D
authors.lastname: Na
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Korea. tchun@korea.ac.kr.
authors.forename: Taehoon
authors.initials: T
authors.lastname: Chun
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Korea. ys-lee@korea.ac.kr.
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D018173:Circoviridae Infections / Q000235:genetics / Q000662:veterinary* / Q000821:virology; D017925:Circovirus / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D063990:Gene Ontology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016366:Open Reading Frames; D053570:Porcine Postweaning Multisystemic Wasting Syndrome / Q000235:genetics* / Q000821:virology; D013552:Swine; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D014764:Viral Proteins