Human papillomavirus type 16 infection activates the host serine arginine protein kinase 1 (SRPK1) - splicing factor axis

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
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 Griffiths, Megan and Faizo, Arwa Ali A
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 > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > 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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630Quinquennial Core FundsMassimo PalmariniMedical Research Council (MRC)MC_UU_12014/9III-MRC-GU CVR Support Services