title: bcl-2 acts early to restrict Semliki Forest virus replication and delays virus-induced programmed cell death.
abstract: As characterized by morphological assessment and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, Semliki Forest virus (SFV) infection of rat prostatic adenocarcinoma cells triggers an apoptotic cell response. Cell death proceeded more rapidly following infection with the neurovirulent L10 strain of SFV than with the avirulent A7 strain. Overexpression of the antiapoptotic proto-oncogene bcl-2 allowed survival of cultures infected with either strain of virus. bcl-2 overexpression drastically reduced the numbers of productively infected cells within the cultures. In situ hybridization for viral message-sense RNA coupled with immunostaining for viral protein indicated that bcl-2 functions at an early stage of the virus life cycle, at entry, pretranscriptional events or at transcription, to inhibit virus replication. Double-immunofluorescent labeling for bcl-2 and viral glycoproteins revealed double-positive cells, demonstrating that with time, this early block in replication can be overcome. These productively infected bcl-2-expressing cells do, with time, undergo apoptosis. As a result of changing the balance between cell death and cell division by restricting productive virus replication and delaying virus-induced cell death, bcl-2 expression led to the establishment of chronically infected cell lines which could be passaged.
authors.affiliation: Department of Veterinary Pathology, University of Edinburgh, United Kingdom.
authors.forename: M F
authors.initials: MF
authors.lastname: Scallan
authors.forename: T E
authors.initials: TE
authors.lastname: Allsopp
authors.forename: J K
authors.initials: JK
authors.lastname: Fazakerley
mesh_terms: D018354:Alphavirus Infections / Q000473:pathology / Q000821:virology*; D000818:Animals; D017209:Apoptosis; D015967:Gene Expression Regulation, Viral; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D012672:Semliki forest virus / Q000502:physiology*; D014779:Virus Replication
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2