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

Author

Listed:
  • Jie Xu

    (Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania)

  • Yan Sun

    (Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania)

  • Yize Li

    (Department of Microbiology, Perelman School of Medicine, University of Pennsylvania)

  • Gordon Ruthel

    (Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania)

  • Susan R. Weiss

    (Department of Microbiology, Perelman School of Medicine, University of Pennsylvania)

  • Arjun Raj

    (Department of Bioengineering, School of Engineering, University of Pennsylvania)

  • Daniel Beiting

    (Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania)

  • Carolina B. López

    (Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania)

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.

Suggested Citation

  • Jie Xu & Yan Sun & Yize Li & Gordon Ruthel & Susan R. Weiss & Arjun Raj & Daniel Beiting & Carolina B. López, 2017. "Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00909-6
    DOI: 10.1038/s41467-017-00909-6
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    Cited by:

    1. Trent J Bosma & Konstantinos Karagiannis & Luis Santana-Quintero & Natalia Ilyushina & Tatiana Zagorodnyaya & Svetlana Petrovskaya & Majid Laassri & Raymond P Donnelly & Steven Rubin & Vahan Simonyan , 2019. "Identification and quantification of defective virus genomes in high throughput sequencing data using DVG-profiler, a novel post-sequence alignment processing algorithm," PLOS ONE, Public Library of Science, vol. 14(5), pages 1-34, May.

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