Graham, S. , Mole, S., Faizo, A. A. A., Hernandez-Lopez, H., Griffiths, M. , Stevenson, A. and Roberts, S. (2020) Human papillomavirus type 16 infection activates the host serine arginine protein kinase 1 (SRPK1) - splicing factor axis. Journal of General Virology, 101(5), pp. 523-532. (doi: 10.1099/jgv.0.001402) (PMID:32182205)
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Abstract
The infectious life cycle of human papillomaviruses (HPVs) is tightly linked to keratinocyte differentiation. Evidence suggests a sophisticated interplay between host gene regulation and virus replication. Alternative splicing is an essential process for host and viral gene expression, and is generally upregulated by serine arginine-rich splicing factors (SRSFs). SRSF activity can be positively or negatively controlled by cycles of phosphorylation/dephosphorylation. Here we show that HPV16 infection leads to accumulation of the paradigm SRSF protein, SRSF1, in the cytoplasm in a keratinocyte differentiation-specific manner. Moreover, HPV16 infection leads to increased levels of cytoplasmic and nuclear phosphorylated SRSF1. SR protein kinase 1 (SRPK1) phosphorylates SRSF1. Similar to HPV upregulation of SRSF1, we demonstrate HPV upregulation of SRPK1 via the viral E2 protein. SRPK1 depletion or drug inhibition of SRPK1 kinase activity resulted in reduced levels of SRSF1, suggesting that phosphorylation stabilizes the protein in differentiated HPV-infected keratinocytes. Together, these data indicate HPV infection stimulates the SRPK1–SRSF axis in keratinocytes.
| Item Type: | Articles |
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| Additional Information: | Funding information This work was funded by a studentship from the Wellcome Trust to S.M., a PhD studentship from Conacyt Mexico to H.H.L. and a PhD studentship from the Saudi Arabia Cultural Bureau (K1513) to A.A.A.F. We acknowledge funding from the Medical Research Council (MC_UU_12014) as core funding for the MRC University of Glasgow Centre for Virus Research. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Stevenson, Mr Andrew and Graham, Professor Sheila and Faizo, Arwa Ali A and Griffiths, Dr Megan |
| Authors: | Graham, S., Mole, S., Faizo, A. A. A., Hernandez-Lopez, H., Griffiths, M., Stevenson, A., and Roberts, S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Journal of General Virology |
| Publisher: | Society for General Microbiology |
| ISSN: | 0022-1317 |
| ISSN (Online): | 1465-2099 |
| Published Online: | 13 March 2020 |
| Copyright Holders: | Copyright © 2020 The Authors |
| First Published: | First published in Journal of General Virology 101:523-532 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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