Skip to content

Research at St Andrews

Resolution of the cellular proteome of the nucleocapsid protein from a highly pathogenic isolate of porcine reproductive and respiratory syndrome virus identifies PARP-1 as a cellular target whose interaction is critical for virus biology

Research output: Contribution to journalArticle

Author(s)

Long Liu, Zoe Lear, David J Hughes, Weining Wu, En-Min Zhou, Adrian Whitehouse, Hongying Chen, Julian A Hiscox

School/Research organisations

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to the swine industry and food security worldwide. The nucleocapsid (N) protein is a major structural protein of PRRSV. The primary function of this protein is to encapsidate the viral RNA genome, and it is also thought to participate in the modulation of host cell biology and recruitment of cellular factors to facilitate virus infection. In order to the better understand these latter roles the cellular interactome of PRRSV N protein was defined using label free quantitative proteomics. This identified several cellular factors that could interact with the N protein including poly [ADP-ribose] polymerase 1 (PARP-1), a cellular protein, which can add adenosine diphosphate ribose to a protein. Use of the PARP-1 small molecule inhibitor, 3-AB, in PRRSV infected cells demonstrated that PARP-1 was required and acted as an enhancer factor for virus biology. Serial growth of PRRSV in different concentrations of 3-AB did not yield viruses that were able to grow with wild type kinetics, suggesting that by targeting a cellular protein crucial for virus biology, resistant phenotypes did not emerge. This study provides further evidence that cellular proteins, which are critical for virus biology, can also be targeted to ablate virus growth and provide a high barrier for the emergence of drug resistance.
Close

Details

Original languageEnglish
Pages (from-to)109-119
Number of pages10
JournalVeterinary Microbiology
Volume176
Issue number1-2
Early online date30 Dec 2014
DOIs
Publication statusPublished - 23 Mar 2015

    Research areas

  • PRRSV, Nucleocapsid, PARP-1, Antivirus, 3-AB, Proteome

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. Contribution of the KSHV and EBV lytic cycles to tumourigenesis

    Manners, O., Murphy, J., Coleman, A., Hughes, D. J. & Whitehouse, A., Oct 2018, In : Current Opinion in Virology. 32, p. 60-70

    Research output: Contribution to journalReview article

  3. Isolation of isoform-specific binding proteins (Affimers) by phage display using negative selection

    Tang, A. A-S., Tiede, C., Hughes, D. J., McPherson, M. J. & Tomlinson, D. C., 14 Nov 2017, In : Science Signaling. 10, 505, 12 p., eaan0868.

    Research output: Contribution to journalArticle

  4. Generation of specific inhibitors of SUMO-1- and SUMO-2/3-mediated protein-protein interactions using Affimer (Adhiron) technology

    Hughes, D. J., Tiede, C., Penswick, N., Ah-San Tang, A., Trinh, C. H., Mendal, U., Zajac, K. Z., Gaule, T., Howell, G., Edwards, T. A., Duan, J., Feyfant, E., McPhereson, M. J., Tomlinson, D. C. & Whitehouse, A., 14 Nov 2017, In : Science Signaling. 10, 505, 14 p., eaaj2005.

    Research output: Contribution to journalArticle

  5. ARID3B: a novel regulator of the Kaposi’s sarcoma-associated herpesvirus lytic cycle

    Wood, J., Boyne, J., Paulus, C., Jackson, B., Nevels, M. M., Whitehouse, A. & Hughes, D. J., Oct 2016, In : Journal of Virology. 90, 20, p. 9543-9555

    Research output: Contribution to journalArticle

Related by journal

  1. Comparative sequence analysis of the capsular polysaccharide loci of Actinobacillus pleuropneumoniae serovars 1-18, and development of two multiplex PCRs for comprehensive capsule typing

    Bossé, J. T., Li, Y., Fernandez Crespo, R., Lacouture, S., Gottschalk, M., Sárközi, R., Fodor, L., Casas Amoribieta, M., Angen, Ø., Nedbalcova, K., Holden, M. T. G., Maskell, D. J., Tucker, A. W., Wren, B. W., Rycroft, A. N., Langford, P. R. & BRaDP1T Consortium, Jul 2018, In : Veterinary Microbiology. 220, p. 83-89 7 p.

    Research output: Contribution to journalArticle

  2. Proposal of serovars 17 and 18 of Actinobacillus pleuropneumoniae based on serological and genotypic analysis

    Bossé, J. T., Li, Y., Sárközi, R., Fodor, L., Lacouture, S., Gottschalk, M., Amoribieta, M. C., Angen, Ø., Nedbalcova, K., Holden, M. T. G., Maskell, D. J., Tucker, A. W., Wren, B. W., Rycroft, A. N., Langford, P. R. & BRaDP1T Consortium, Apr 2018, In : Veterinary Microbiology. 217, p. 1-6

    Research output: Contribution to journalArticle

  3. Diversity of Streptococcus equi subsp. zooepidemicus strains isolated from the Spanish sheep and goat population and the identification, function and prevalence of a novel arbutin utilisation system

    Steward, K. F., Robinson, C., Holden, M. T. G., Harris, S. R., Ros, A. F., Pérez, G. C., Baselga, R. & Waller, A. S., Aug 2017, In : Veterinary Microbiology. 207, p. 231-238 8 p.

    Research output: Contribution to journalArticle

  4. Characterisation of a mobilisable plasmid conferring florfenicol and chloramphenicol resistance in Actinobacillus pleuropneumoniae

    Bossé, J. T., Li, Y., Atherton, T. G., Walker, S., Williamson, S. M., Rogers, J., Chaudhuri, R. R., Weinert, L. A., Holden, M. T. G., Maskell, D. J., Tucker, A. W., Wren, B. W., Rycroft, A. N., Langford, P. R. & BRaDP1T Consortium, 5 Aug 2015, In : Veterinary Microbiology. 178, 3-4, p. 279-82 4 p.

    Research output: Contribution to journalArticle

ID: 164146164

Top