Skip to content

Research at St Andrews

Innate intracellular antiviral responses restrict the amplification of defective virus genomes of parainfluenza virus type 5

Research output: Contribution to journalArticle

DOI

Open Access permissions

Open

Author(s)

Elizabeth B Wignall-Fleming, Andri Vasou, Dan Young, John A L Short, David J Hughes, Steve Goodbourn, Richard E Randall

School/Research organisations

Abstract

During the replication of parainfluenza virus type 5 (PIV5) copyback defective virus genomes (DVGs) are erroneously produced and are packaged into "infectious" virus particles. Copyback DVGs are primary inducers of innate intracellular responses, including the interferon (IFN) response. Whilst DVGs can interfere with the replication of non-defective (ND) virus genomes and activate the IFN-induction cascade before ND PIV5 can block the production of IFN, we demonstrate that the converse is also true, i.e. high levels of ND virus can block the ability of DVGs to activate the IFN-induction cascade. By following the replication and amplification of DVGs in A549 cells that are deficient in a variety of innate intracellular antiviral responses, we show that DVGs induce an uncharacterised IFN-independent innate response(s) that limits their replication. High throughput sequencing was used to characterise the molecular structure of copyback DVGs. Whilst there appears to be no sequence-specific break or rejoining points for the generation of copyback DVGs, our finds suggest that there are region, size and/or structural preferences selected for during for their amplification.

Importance Copyback defective virus genomes (DVGs) are powerful inducers of innate immune responses both in vitro and in vivo. They impact the outcome of natural infections, may help drive virus-host co-evolution, and promote virus persistence. Due to their potent interfering and immunostimulatory properties, DVGs may also be used therapeutically as antivirals and vaccine adjuvants. However, little is known of the host cell restrictions which limit their amplification. We show here that the generation of copyback DVGs readily occurs during parainfluenza virus type 5 (PIV5) replication but that their subsequent amplification is restricted by the induction of innate intracellular responses. Molecular characterisation of PIV5 copyback DVGs suggests that whilst there are no genome sequence specific breaks or rejoin points for the generation of copyback DVGs, genome region, size and structural preferences are selected for during their evolution and amplification.
Close

Details

Original languageEnglish
Article number00246-20
Number of pages15
JournalJournal of Virology
Volume94
Issue number13
Early online date16 Jun 2020
DOIs
Publication statusE-pub ahead of print - 16 Jun 2020

    Research areas

  • Defective virus genomes, Host cell restriction, Innate immunity, Paramyxoviruses

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Analysis of paramyxovirus transcription and replication by high-throughput sequencing

    Wignall-Fleming, E. B., Hughes, D. J., Vattipally, S., Modha, S., Goodbourn, S., Davison, A. J. & Randall, R. E., 13 Aug 2019, In : Journal of Virology. 93, 17, 17 p., e00571-19.

    Research output: Contribution to journalArticle

  2. Unusual, stable replicating viruses generated from mumps virus cDNA clones

    Bamford, C., Wignall-Fleming, E., Sreenu, V. B., Randall, R., Duprex, P. & Rima, B., 5 Jul 2019, In : PLoS ONE. 14, 7, 14 p., e0219168.

    Research output: Contribution to journalArticle

  3. The switch between acute and persistent paramyxovirus infection caused by single amino acid substitutions in the RNA polymerase P subunit

    Young, D. F., Wignall-Fleming, E. B., Busse, D. C., Pickin, M. J., Hankinson, J., Randall, E. M., Tavendale, A., Davison, A. J., Lamont, D., Tregoning, J. S., Goodbourn, S. & Randall, R. E., 11 Feb 2019, In : PLoS Pathogens. 15, 2, 24 p., e1007561.

    Research output: Contribution to journalArticle

  4. Modular cell-based platform for high throughput identification of compounds that inhibit a viral interferon antagonist of choice

    Vasou, A., Paulus, C., Narloch, J., Gage, Z. O., Rameix-Welti, M-A., Eléouët, J-F., Nevels, M., Randall, R. E. & Adamson, C. S., Feb 2018, In : Antiviral Research. 150, p. 79-92

    Research output: Contribution to journalArticle

Related by journal

  1. The BHLF1 locus of Epstein-Barr virus contributes to viral latency and B-cell immortalization

    Yetming, K. D., Lupey-Green, L. N., Biryukov, S., Hughes, D. J., Marendy, E. M., Miranda, J. J. L. & Sample, J. T., 24 Jun 2020, In : Journal of Virology. Latest Articles, JVI01215-20.

    Research output: Contribution to journalArticle

  2. Analysis of paramyxovirus transcription and replication by high-throughput sequencing

    Wignall-Fleming, E. B., Hughes, D. J., Vattipally, S., Modha, S., Goodbourn, S., Davison, A. J. & Randall, R. E., 13 Aug 2019, In : Journal of Virology. 93, 17, 17 p., e00571-19.

    Research output: Contribution to journalArticle

  3. Human cytomegalovirus immediate early 1 protein causes loss of SOX2 from neural progenitor cells by trapping unphosphorylated STAT3 in the nucleus

    Wu, C-C., Jiang, X., Wang, X-Z., Liu, X-J., Li, X-J., Yang, B., Ye, H-Q., Harwardt, T., Jiang, M., Xia, H-M., Wang, W., Britt, W. J., Paulus, C., Nevels, M. M. & Luo, M-H., Sep 2018, In : Journal of Virology. 92, 17, e00340-18.

    Research output: Contribution to journalArticle

  4. Association of human papillomavirus 16 E2 with Rad50-interacting protein 1 enhances viral DNA replication

    Campos-León, K., Wijendra, K., Siddiqa, A., Pentland, I., Feeney, K. M., Knapman, A., Davies, R., Androphy, E. J. & Parish, J. L., Mar 2017, In : Journal of Virology. 91, 5, 18 p., e02305-16.

    Research output: Contribution to journalArticle

Related by journal

  1. Journal of Virology (Journal)

    Richard Michael Elliott (Editor)

    20052013

    Activity: Publication peer-review and editorial work typesEditor of research journal

ID: 267482669

Top