Herpes simplex virus blocks host transcription termination via the bimodal activities of ICP27

Xiuye Wang, Thomas Hennig, Adam W. Whisnant, Florian Erhard, Bhupesh K. Prusty, Caroline C. Friedel, Elmira Forouzmand, William Hu, Luke Erber, Yue Chen, Rozanne M. Sandri-Goldin, Lars Dölken, Yongsheng Shi

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Infection by viruses, including herpes simplex virus-1 (HSV-1), and cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes. However, the underlying mechanisms remain unclear. Here, we demonstrate that the HSV-1 immediate early protein ICP27 induces DoTT by directly binding to the essential mRNA 3’ processing factor CPSF. It thereby induces the assembly of a dead-end 3’ processing complex, blocking mRNA 3’ cleavage. Remarkably, ICP27 also acts as a sequence-dependent activator of mRNA 3’ processing for viral and a subset of host transcripts. Our results unravel a bimodal activity of ICP27 that plays a key role in HSV-1-induced host shutoff and identify CPSF as an important factor that mediates regulation of transcription termination. These findings have broad implications for understanding the regulation of transcription termination by other viruses, cellular stress and cancer.

Original languageEnglish (US)
Article number293
JournalNature communications
Issue number1
StatePublished - Jan 15 2020

Bibliographical note

Funding Information:
We would like to thank David M. Knipe for providing reagents, Neal deLuca for providing his extended set of HSV-1 deletion mutants and UCI GHTF for sequencing. This study was supported by the following grants: NIH GM090056 and GM128441 to Y.S. ERC Consolidator award (ERC-2016-CoG 721016-HERPES) and DFG grant DFG (1275/6-1 to L.D.). A.W.W. was the recipient of a generous grant from the Alexander von Humboldt Foundation.

Publisher Copyright:
© 2020, The Author(s).


  • Animals
  • Cell Line
  • Cleavage And Polyadenylation Specificity Factor/metabolism
  • HeLa Cells
  • Herpes Simplex/genetics
  • Herpesvirus 1, Human/genetics
  • Host-Pathogen Interactions/genetics
  • Humans
  • Immediate-Early Proteins/genetics
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger/genetics
  • Transcription Termination, Genetic

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural


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