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-...Continue Reading
References
Citations
Generation and Functional In Vitro Analysis of Semliki Forest Virus Vectors Encoding TNF-α and IFN-γ
Related Concepts
Related Feeds
BCL-2 Family Proteins
BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis