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.

journal_name

J Virol

journal_title

Journal of virology

authors

Klucking S,Collins AS,Young JA

doi

10.1128/JVI.79.13.8243-8248.2005

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

8243-8

issue

13

eissn

0022-538X

issn

1098-5514

pii

79/13/8243

journal_volume

79

pub_type

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