title: Viral hit and run-oncogenesis: genetic and epigenetic scenarios.
abstract: It is well documented that viral genomes either inserted into the cellular DNA or co-replicating with it in episomal form can be lost from neoplastic cells. Therefore, "hit and run"-mechanisms have been a topic of longstanding interest in tumor virology. The basic idea is that the transient acquisition of a complete or incomplete viral genome may be sufficient to induce malignant conversion of host cells in vivo, resulting in neoplastic development. After eliciting a heritable change in the gene expression pattern of the host cell (initiation), the genomes of tumor viruses may be completely lost, i.e. in a hit and run-scenario they are not necessary for the maintenance of the malignant state. The expression of viral oncoproteins and RNAs may interfere not only with regulators of cell proliferation, but also with DNA repair mechanisms. DNA recombinogenic activities induced by tumor viruses or activated by other mechanisms may contribute to the secondary loss of viral genomes from neoplastic cells. Viral oncoproteins can also cause epigenetic dysregulation, thereby reprogramming cellular gene expression in a heritable manner. Thus, we expect that epigenetic scenarios of viral hit and run-tumorigenesis may facilitate new, innovative experiments and clinical studies in spite of the fact that the regular presence of a suspected human tumor virus in an early phase of neoplastic development and its subsequent regular loss have not been demonstrated yet. We propose that virus-specific "epigenetic signatures", i.e. alterations of the host cell epigenome, especially altered DNA methylation patterns, may help to identify viral hit and run-oncogenic events, even after the complete loss of tumor viruses from neoplastic cells.
authors.affiliation: Institute for Medical Microbiology and Hygiene of the University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, Germany. Hans-Helmut.Niller@klinik.uni-regensburg.de
authors.forename: Hans Helmut
authors.initials: HH
authors.lastname: Niller
authors.forename: Hans
authors.initials: H
authors.lastname: Wolf
authors.forename: Janos
authors.initials: J
authors.lastname: Minarovits
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D004260:DNA Repair; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D009858:Oncogenic Viruses / Q000378:metabolism; D011995:Recombination, Genetic; D045567:VDJ Recombinases / Q000378:metabolism
chemical_list: D002843:Chromatin; D045567:VDJ Recombinases