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

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

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Article numbere02305-16
JournalJournal of virology
Volume91
Issue number5
DOIs
StatePublished - 2017

Keywords

  • E2
  • Papillomavirus
  • Rad50-interacting protein
  • Replication

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'Association of human papillomavirus 16 E2 with Rad50-interacting protein 1 enhances viral DNA replication'. Together they form a unique fingerprint.

  • Cite this

    Campos-León, K., Wijendra, K., Siddiqa, A., Pentland, I., Feeney, K. M., Knapman, A., Davies, R., Androphy, E. J., & Parish, J. L. (2017). Association of human papillomavirus 16 E2 with Rad50-interacting protein 1 enhances viral DNA replication. Journal of virology, 91(5), [e02305-16]. https://doi.org/10.1128/JVI.02305-16