title: A novel recombinant papillomavirus genome enabling in vivo RNA interference reveals that YB-1, which interacts with the viral regulatory protein E2, is required for CRPV-induced tumor formation in vivo.
abstract: YB-1 is considered a negative prognostic marker for different types of cancer. Increased YB-1 protein levels in tumor cells indicate a worse prognosis. In a preceding study comparing the transcripts of CRPV-induced benign papillomas to mRNA levels of malignant epithelial tumors, we identified YB-1 as a gene that is up-regulated in papillomavirus-associated carcinomas and which causes an invasive phenotype in CRPV-positive cells in vitro. Here we demonstrate that YB-1 is a previously unknown factor required for papillomavirus-induced tumor development in the rabbit animal model system. By infecting the animals with a novel recombinant shRNA-expressing CRPV genome, we show that knock-down of YB-1 dramatically reduces papillomavirus-dependent tumor formation in vivo. Consistent with previous reports showing a nuclear distribution of YB-1 proteins as a hallmark of malignancy, we demonstrate a predominantly nuclear localization of YB-1 in CRPV-immortalized cells. Furthermore we give evidence of YB-1 regulating the CRPV URR and thereby viral gene expression and we identified YB-1 as a novel interactor of the CRPV regulatory protein E2. Taken together we hypothesize that YB-1 is essential for papillomavirus-induced tumor formation probably by regulating viral gene expression including expression of the oncogenes E6 and E7.
authors: Medical Virology, Division of Experimental Virology, University Hospital Tübingen Germany.
authors: Natalie
authors: N
authors: Leiprecht
authors: Medical Virology, Division of Experimental Virology, University Hospital Tübingen Germany.
authors: Ekaterina
authors: E
authors: Notz
authors: Medical Virology, Division of Experimental Virology, University Hospital Tübingen Germany.
authors: Johanna
authors: J
authors: Schuetz
authors: Medical Virology, Division of Experimental Virology, University Hospital Tübingen Germany.
authors: Juliane
authors: J
authors: Haedicke
authors: Medical Virology, Division of Experimental Virology, University Hospital Tübingen Germany.
authors: Frank
authors: F
authors: Stubenrauch
authors: Medical Virology, Division of Experimental Virology, University Hospital Tübingen Germany.
authors: Thomas
authors: T
authors: Iftner
keywords: CRPV; E2; Papillomavirus; YB-1; in vivo; protein-protein interaction; rabbit; viral transcription