Proteotype profiling unmasks a viral signalling network essential for poxvirus assembly and transcriptional competence

Karel Novy, Samuel Kilcher, Ulrich Omasits, Christopher Karl Ernst Bleck, Corina Beerli, Jakob Vowinckel, Caroline K. Martin, Mohammedyaseen Syedbasha, Alessio Maiolica, Ian White, Jason Mercer*, Bernd Wollscheid

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


To orchestrate context-dependent signalling programmes, poxviruses encode two dual-specificity enzymes, the F10 kinase and the H1 phosphatase. These signalling mediators are essential for poxvirus production, yet their substrate profiles and systems-level functions remain enigmatic. Using a phosphoproteomic screen of cells infected with wild-type, F10 and H1 mutant vaccinia viruses, we systematically defined the viral signalling network controlled by these enzymes. Quantitative cross-comparison revealed 33 F10 and/or H1 phosphosites within 17 viral proteins. Using this proteotype dataset to inform genotype-phenotype relationships, we found that H1-deficient virions harbour a hidden hypercleavage phenotype driven by reversible phosphorylation of the virus protease I7 (S134). Quantitative phosphoproteomic profiling further revealed that the phosphorylation-dependent activity of the viral early transcription factor, A7 (Y367), underlies the transcription-deficient phenotype of H1 mutant virions. Together, these results highlight the utility of combining quantitative proteotype screens with mutant viruses to uncover proteotype-phenotype-genotype relationships that are masked by classical genetic studies.

Original languageEnglish
Pages (from-to)588-599
Number of pages12
JournalNature Microbiology
Issue number5
Early online date9 Apr 2018
Publication statusPublished - May 2018

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology


Dive into the research topics of 'Proteotype profiling unmasks a viral signalling network essential for poxvirus assembly and transcriptional competence'. Together they form a unique fingerprint.

Cite this