title: An ovine adenovirus vector lacks transforming ability in cells that are transformed by AD5 E1A/B sequences.
abstract: Adenoviruses of the Mastadenovirus and Aviadenovirus genera are able to transform certain cell types and induce tumor formation in susceptible animals. For the mastadenoviruses the E1A/B sequences are largely responsible for these properties but E4 sequences may also be involved. The transforming sequences of the aviadenoviruses, which lack E1A/B and E4 homologues, have not yet been fully identified. The recent proposal for a third genus of adenoviruses, which apparently lack an E1A homologue and have weak E1B homology, prompted an examination of the transforming properties of ovine adenovirus OAV287 (OAV), the prototype member of the new group. When OAV and human adenovirus type 5 (Ad5) were used to infect primary rat embryo cells, transformed foci developed in Ad5- but not in OAV-infected cultures. Similarly, after plasmid transfection, baby rat kidney cells were transformed by Ad5 E1A/B but not by OAV sequences. When CSL503 cells, an ovine cell line that is permissive for OAV, were transfected with Ad5 E1A/B sequences, transformed foci again appeared. However, plasmids or fragments containing complete or partial OAV genome sequences did not detectably transform CSL503 cells under the same conditions. When Ad5 E1A/B sequences were incorporated into the complete OAV genome and transfected, transformed clones were again obtained, showing that the gene dosage and transfection conditions were not limiting for transformation. The provision of Ad5 E1A and OAV sequences in combination marginally increased the number of morphologically altered foci in baby rat kidney cells but failed to induce multilayered focus formation. The data suggest that OAV lacks transforming functions in the cell types examined. Additional information suggesting that OAV may have a fundamentally distinct strategy for replication compared with other Ads is discussed.
authors.affiliation: CSIRO, Molecular Science, North Ryde, New South Wales, 2113, Australia.
authors.forename: Z Z
authors.initials: ZZ
authors.lastname: Xu
authors.forename: M
authors.initials: M
authors.lastname: Nevels
authors.forename: E S
authors.initials: ES
authors.lastname: MacAvoy
authors.forename: L J
authors.initials: LJ
authors.lastname: Lockett
authors.forename: D
authors.initials: D
authors.lastname: Curiel
authors.forename: T
authors.initials: T
authors.lastname: Dobner
authors.forename: G W
authors.initials: GW
authors.lastname: Both
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics* / Q000502:physiology; D000818:Animals; D002460:Cell Line; D048429:Cell Size; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D005814:Genes, Viral / Q000235:genetics / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology; D016679:Genome, Viral; D007668:Kidney / Q000196:embryology / Q000473:pathology / Q000821:virology; D008168:Lung / Q000473:pathology / Q000821:virology; D010957:Plasmids / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D051381:Rats; D012756:Sheep / Q000821:virology; D014162:Transfection; D014410:Tumor Stem Cell Assay
chemical_list: D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D012367:RNA, Viral