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Volume 101, Issue 5

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

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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cervical cancer , epithelial differentiation , human papillomavirus , infection and tumour progression
Funding
This study was supported by the:
  • Saudi Arabia Cultural Bureau in London (Award K1513)
    • Principle Award Recipient: Arwa Faizo
  • Conacyt (Award 309211)
    • Principle Award Recipient: Hegel Hernandez-Lopez
  • Wellcome Trust (Award Too old to track)
    • Principle Award Recipient: Not Applicable
© 2020 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2020-03-13
2024-04-24
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Human papillomavirus type 16 infection activates the host serine arginine protein kinase 1 (SRPK1) – splicing factor axis
J. Gen. Virol. 101, 523 (2020); https://doi.org/10.1099/jgv.0.001402
/content/journal/jgv/10.1099/jgv.0.001402
/content/journal/jgv/10.1099/jgv.0.001402
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