Skip to content

Research at St Andrews

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

Research output: Contribution to journalArticlepeer-review

DOI

Open Access permissions

Open

Author(s)

Karen Campos-León, Kalpanee Wijendra, Abida Siddiqa, Ieisha Pentland, Katherine M. Feeney, Alison Knapman, Rachel Davies, Elliot J. Androphy, Joanna L. Parish

School/Research organisations

Abstract

Rad50-interacting protein 1 (Rint1) associates with the DNA damage response protein Rad50 during the transition from the S phase to the G2/M phase and functions in radiation-induced G2 checkpoint control. It has also been demonstrated that Rint1 is essential in vesicle trafficking from the Golgi apparatus to the endoplasmic reticulum (ER) through an interaction with Zeste-White 10 (ZW10). We have isolated a novel interaction between Rint1 and the human papillomavirus 16 (HPV16) transcription and replication factor E2. E2 binds to Rint1 within its ZW10 interaction domain, and we show that in the absence of E2, Rint1 is localized to the ER and associates with ZW10. E2 expression results in a disruption of the Rint1-ZW10 interaction and an accumulation of nuclear Rint1, coincident with a significant reduction in vesicle movement from the ER to the Golgi apparatus. Interestingly, nuclear Rint1 and members of the Mre11/Rad50/Nbs1 (MRN) complex were found in distinct E2 nuclear foci, which peaked during mid-S phase, indicating that the recruitment of Rint1 to E2 foci within the nucleus may also result in the recruitment of this DNA damage-sensing protein complex. We show that exogenous Rint1 expression enhances E2-dependent virus replication. Conversely, the overexpression of a truncated Rint1 protein that retains the E2 binding domain but not the Rad50 binding domain acts as a dominant negative inhibitor of E2-dependent HPV replication. Put together, these experiments demonstrate that the interaction between Rint1 and E2 has an important function in HPV replication.

Close

Details

Original languageEnglish
Article numbere02305-16
Number of pages18
JournalJournal of Virology
Volume91
Issue number5
Early online date28 Dec 2016
DOIs
Publication statusPublished - Mar 2017

    Research areas

  • E2, Papillomavirus, Rad50-interacting protein, Replication

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

View graph of relations

Related by author

  1. Stabilization of stalled DNA replication forks by the BRCA2 breast cancer susceptibility protein

    Lomonosov, M., Anand, S., Sangrithi, M., Davies, R. & Venkitaraman, A. R., 15 Dec 2003, In: Genes & Development. 17, 24, p. 3017-22 6 p.

    Research output: Contribution to journalArticlepeer-review

  2. Identification of WTAP, a novel Wilms' tumour 1-associating protein

    Little, N. A., Hastie, N. D. & Davies, R. C., 22 Sep 2000, In: Human Molecular Genetics. 9, 15, p. 2231-9 9 p.

    Research output: Contribution to journalArticlepeer-review

  3. Did nucleotides or amino acids drive evolutionary conservation of the WT1 +/-KTS alternative splice?

    Davies, R. C., Bratt, E. & Hastie, N. D., 1 May 2000, In: Human Molecular Genetics. 9, 8, p. 1177-83 7 p.

    Research output: Contribution to journalArticlepeer-review

  4. Multiple roles for the Wilms' tumor suppressor, WT1

    Davies, R., Moore, A., Schedl, A., Bratt, E., Miyahawa, K., Ladomery, M., Miles, C., Menke, A., van Heyningen, V. & Hastie, N., 1 Apr 1999, In: Cancer Research. 59, 7 Suppl, p. 1747s-1750s; discussion 1751s

    Research output: Contribution to journalReview articlepeer-review

  5. WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes

    Davies, R. C., Calvio, C., Bratt, E., Larsson, S. H., Lamond, A. I. & Hastie, N. D., 15 Oct 1998, In: Genes & Development. 12, 20, p. 3217-25 9 p.

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. Journal of Virology (Journal)

    Richard Michael Elliott (Editor)

    20052013

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

Related by journal

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

    Wignall-Fleming, E. B., Vasou, A., Young, D., Short, J. A. L., Hughes, D. J., Goodbourn, S. & Randall, R. E., 16 Jun 2020, In: Journal of Virology. 94, 13, 15 p., 00246-20.

    Research output: Contribution to journalArticlepeer-review

  2. 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 journalArticlepeer-review

  3. 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 journalArticlepeer-review

  4. 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 journalArticlepeer-review

ID: 249566827

Top