Skip to content

Research at St Andrews

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

Research output: Research - peer-reviewArticle


Open Access permissions



Jennifer Wood, James Boyne, Christina Paulus, Brian Jackson, Michael Martin Nevels, Adrian Whitehouse, David John Hughes

School/Research organisations


KSHV is the causative agent of commonly fatal malignancies of immuno-compromised individuals, including primary effusion lymphoma (PEL) and Kaposi’s sarcoma (KS). A hallmark of all herpesviruses is their biphasic lifecycle – viral latency and the productive lytic cycle, and it is well established that reactivation of the KSHV lytic cycle is associated with KS pathogenesis. Therefore, a thorough appreciation of the mechanisms that govern reactivation is required to better understand disease progression. The viral protein, replication and transcription activator (RTA), is the KSHV lytic switch protein due to its ability to drive the expression of various lytic genes, leading to reactivation of the entire lytic cycle. While the mechanisms for activating lytic gene expression have received much attention, how RTA impacts on cellular function is less well understood. To address this, we developed a cell line with doxycycline-inducible RTA expression and applied SILAC-based quantitative proteomics. Using this methodology, we have identified a novel cellular protein (AT-rich interacting domain containing 3B, ARID3B) whose expression was enhanced by RTA and that relocalised to replication compartments upon lytic reactivation. We also show that siRNA knockdown or overexpression of ARID3B led to an enhancement or inhibition of lytic reactivation, respectively. Furthermore, DNA affinity and chromatin immunoprecipitation assays demonstrated that ARID3B specifically interacts with A/T-rich elements in the KSHV origin of lytic replication (oriLyt), and this was dependent on lytic cycle reactivation. Therefore, we have identified a novel cellular protein whose expression is enhanced by KSHV RTA with the ability to inhibit KSHV reactivation.


Original languageEnglish
Pages (from-to)9543-9555
JournalJournal of Virology
Issue number20
Early online date10 Aug 2016
StatePublished - Oct 2016

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

View graph of relations

Related by author

  1. 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: Research - peer-reviewArticle

  2. Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

    Harwardt, T., Lukas, S., Zenger, M., Reitberger, T., Danzer, D., Übner, T., Munday, D. C., Nevels, M. & Paulus, C. 7 Jul 2016 In : PLoS Pathogens. 12, 7, 39 p., e1005748

    Research output: Research - peer-reviewArticle

  3. The proteome of human cytomegalovirus virions and dense bodies is conserved across different strains

    Büscher, N., Paulus, C., Nevels, M., Tenzer, S. & Plachter, B. Jun 2015 In : Medical Microbiology and Immunology. 204, 3, p. 285-293 9 p.

    Research output: Research - peer-reviewArticle

  4. Human cytomegalovirus major immediate early 1 protein targets host chromosomes by docking to the acidic pocket on the nucleosome surface

    Mücke, K., Paulus, C., Bernhardt, K., Gerrer, K., Schön, K., Fink, A., Sauer, E-M., Asbach-Nitzsche, A., Harwardt, T., Kieninger, B., Kremer, W., Kalbitzer, H. R. & Nevels, M. Jan 2014 In : Journal of Virology. 88, 2, p. 1228-48 21 p.

    Research output: Research - peer-reviewArticle

  5. Human cytomegalovirus IE1 protein disrupts interleukin-6 signaling by sequestering STAT3 in the nucleus

    Reitsma, J. M., Sato, H., Nevels, M., Terhune, S. S. & Paulus, C. Oct 2013 In : Journal of Virology. 87, 19, p. 10763-76 14 p.

    Research output: Research - peer-reviewArticle

Related by journal

  1. 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: Research - peer-reviewArticle

  2. Assessing host-virus codivergence for close relatives of Merkel cell polyomavirus infecting African great apes

    Madinda, N. F. , Ehlers, B. , Wertheim, J. O. , Akoua-Koffi, C. , Bergl, R. A. , Boesch, C. , Akonkwa, D. B. M. , Eckardt, W. , Fruth, B. , Gillespie, T. R. , Gray, M. , Hohmann, G. , Karhemere, S. , Kujirakwinja, D. , Langergraber, K. , Muyembe, J. J. , Nishuli, R. , Pauly, M. , Petrzelkova, K. J. , Robbins, M. M. & 8 others Todd, A., Schubert, G., Stoinski, T. S., Wittig, R. M., Zuberbühler, K., Peeters, M., Leendertz, F. H. & Calvignac-Spencer, S. Oct 2016 In : Journal of Virology. 90, 19, p. 8531-8541 11 p.

    Research output: Research - peer-reviewArticle

  3. Human IFIT1 inhibits mRNA translation of rubulaviruses but not other members of the Paramyxoviridae family

    Young, D. F., Andrejeva, J., Li, X., Inesta-Vaquera, F., Dong, C., Cowling, V. H., Goodbourn, S. & Randall, R. E. Oct 2016 In : Journal of Virology. 90, 20, p. 9446-9456

    Research output: Research - peer-reviewArticle

  4. Structure-activity relationships of the Human Immunodeficiency Virus Type 1 maturation inhibitor PF-46396

    Murgatroyd, C., Pirrie, L., Fanny Tran, Smith, T. K., Westwood, N. J. & Adamson, C. S. Sep 2016 In : Journal of Virology. 90, 18, p. 8181-8197 17 p.

    Research output: Research - peer-reviewArticle

Related by journal

  1. Journal of Virology (Journal)

    Richard Michael Elliott (Editor)

    Activity: Publication peer-review and editorial workEditor of research journal

ID: 244420079