RT Journal Article
SR Electronic
T1 Replication defective viral genomes exploit a cellular pro-survival mechanism to establish viral persistence
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 120766
DO 10.1101/120766
A1 Jie Xu
A1 Yan Sun
A1 Yize Li
A1 Gordon Ruthel
A1 Susan R. Weiss
A1 Arjun Raj
A1 Daniel Beiting
A1 Carolina B. López
YR 2017
UL http://biorxiv.org/content/early/2017/03/26/120766.abstract
AB Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many infections. However, it is also well established that DVGs facilitate viral persistence. Why and how DVGs interact with the host to achieve these two opposing functions remains unknown. We report that DVGs engage a MAVS-mediated TNF response that selectively protects a subpopulation of cells from death and promotes the establishment of persistent infections. We find that this phenotype results from the dual activities of TNF, which drives apoptosis of highly infected cells while extending the survival of cells enriched in DVGs. The pro-survival effect of TNF depends on the activity of the TNFR2/TRAF1 pathway that is regulated by MAVS signaling. These results identify TNF as a pivotal factor in determining cell fate during a viral infection and delineate a MAVS/TNFR2-mediated mechanism that drives the persistence of otherwise acute viruses.