title: Identification and promoter analysis of PERV LTR subtypes in NIH-miniature pig.
abstract: Porcine endogenous retroviruses (PERVs) are integrated into the genomes of all pigs. Since some PERVs can also infect human cells, they represent a potential risk for xenotransplantation involving pig cells or organs. The long terminal repeat (LTR) elements of PERVs show promoter activity that can affect human functional genes; therefore, we examined these elements in this study. We detected several expressed LTRs in the NIH-miniature pig liver, among which we identified 9 different subtypes. When these LTRs were compared, distinct structures that contained several insertion and deletion (INDEL) events and tandem repeats were identified in the U3 region. The transcriptional activity of the 9 LTR subtypes was analyzed in the PK15 porcine cell line and in the HepG2 and Hep3B human liver cell lines, and transcriptional regulation was found to be different in the 3 cell lines. The D LTR subtype was found to have stronger promoter activity than all other types in 4 different human cell lines (HepG2, Hep3B, U251, and 293). Using computational approaches, the D type was shown to contain 4 transcription factor-binding sites distinct from those in the U3 regions of the other subtypes. Therefore, deletion mutants were constructed and examined by a transient transfection luciferase assay. The results of this analysis indicated that the binding site for the Hand1:E47 transcription factor might play a positive role in the transcriptional regulation of PERV LTR subtype D in human liver cell lines.
authors: Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Korea.
authors: Yi-Deun
authors: YD
authors: Jung
authors: Hong-Seok
authors: HS
authors: Ha
authors: Sang-Je
authors: SJ
authors: Park
authors: Keon-Bong
authors: KB
authors: Oh
authors: Gi-Sun
authors: GS
authors: Im
authors: Tae-Hun
authors: TH
authors: Kim
authors: Hwan-Hoo
authors: HH
authors: Seong
authors: Heui-Soo
authors: HS
authors: Kim
mesh_terms: D025662:Adenoviruses, Porcine / Q000145:classification / Q000235:genetics*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D004279:DNA, Viral; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006321:Heart / Q000821:virology; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000821:virology; D009154:Mutation; D011401:Promoter Regions, Genetic; D013552:Swine; D013556:Swine, Miniature / Q000235:genetics* / Q000821:virology; D020079:Terminal Repeat Sequences; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004279:DNA, Viral; D014157:Transcription Factors; C097341:helix-loop-helix protein, eHAND