Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence

Jie Xu, Yan Sun, Yize Li, Gordon Ruthel, Susan R. Weiss, Arjun Raj, Daniel Beiting, Carolina B. López

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many RNA virus infections. However, DVGs can also facilitate viral persistence. Why and how these two opposing functions of DVGs are achieved remain unknown. Here we report that during Sendai and respiratory syncytial virus infections DVGs selectively protect a subpopulation of cells from death, thereby promoting the establishment of persistent infections. We find that during Sendai virus infection this phenotype results from DVGs stimulating a mitochondrial antiviral-signaling (MAVS)-mediated TNF response that 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.

Original languageEnglish (US)
Article number799
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

genome
Viral Genome
viruses
infectious diseases
Viruses
Genes
Antiviral Agents
Receptors, Tumor Necrosis Factor, Type II
Virus Diseases
RNA Virus Infections
TNF Receptor-Associated Factor 1
Cells
Sendai virus
Respiratory Syncytial Virus Infections
phenotype
immunity
apoptosis
Virus Replication
cells
death

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Xu, Jie ; Sun, Yan ; Li, Yize ; Ruthel, Gordon ; Weiss, Susan R. ; Raj, Arjun ; Beiting, Daniel ; López, Carolina B. / Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence. In: Nature communications. 2017 ; Vol. 8, No. 1.
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Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence. / Xu, Jie; Sun, Yan; Li, Yize; Ruthel, Gordon; Weiss, Susan R.; Raj, Arjun; Beiting, Daniel; López, Carolina B.

In: Nature communications, Vol. 8, No. 1, 799, 01.12.2017.

Research output: Contribution to journalArticle

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