title: Avian sarcoma and leukosis virus cytopathic effect in the absence of TVB death domain signaling.
abstract: The cytopathic effect (CPE) seen with some subgroups of avian sarcoma and leukosis virus (ASLV) is associated with viral Env activation of the death-promoting activity of TVB (a tumor necrosis factor receptor-related receptor that is most closely related to mammalian TNF-related apoptosis-inducing ligand [TRAIL] receptors) and with viral superinfection leading to unintegrated viral DNA (UVD) accumulation, which is presumed to activate a cellular DNA damage response. In this study, we employed cells that express signaling-deficient ASLV receptors to demonstrate that an ASLV CPE can be uncoupled from the death-promoting functions of the TVB receptor. However, these cell-killing events were associated with much higher levels of viral superinfection and DNA accumulation than those seen when the virus used signaling-competent TVB receptors. These findings suggest that a putative cellular DNA damage response that is activated by UVD accumulation might act in concert with the death-signaling pathways activated by Env-TVB interactions to trigger cell death. Such a model is consistent with the well-established synergy that exists between TRAIL-signaling pathways and DNA damage responses which is currently being exploited in cancer therapy regimens.
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Klucking
authors.forename: Asha S
authors.initials: AS
authors.lastname: Collins
authors.forename: John A T
authors.initials: JA
authors.lastname: Young
mesh_terms: D001354:Avian Leukosis Virus / Q000235:genetics / Q000378:metabolism*; D001358:Avian Sarcoma Viruses / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002448:Cell Adhesion; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D004249:DNA Damage; D017931:DNA Primers; D005434:Flow Cytometry; D015686:Gene Products, env / Q000378:metabolism; D006801:Humans; D016133:Polymerase Chain Reaction; D011991:Receptors, Virus / Q000502:physiology*
chemical_list: D017931:DNA Primers; D015686:Gene Products, env; D011991:Receptors, Virus