Vaccinia virus hijacks EGFR signalling to enhance virus spread through rapid and directed infected cell motility

Corina Beerli, Artur Yakimovich, Samuel Kilcher, Glennys V. Reynoso, Gotthold Fläschner, Daniel J. Müller, Heather D. Hickman, Jason Mercer*

*Corresponding author for this work

Research output: Contribution to journalLetterpeer-review

20 Citations (Scopus)


Cell motility is essential for viral dissemination 1 . Vaccinia virus (VACV), a close relative of smallpox virus, is thought to exploit cell motility as a means to enhance the spread of infection 1 . A single viral protein, F11L, contributes to this by blocking RhoA signalling to facilitate cell retraction 2 . However, F11L alone is not sufficient for VACV-induced cell motility, indicating that additional viral factors must be involved. Here, we show that the VACV epidermal growth factor homologue, VGF, promotes infected cell motility and the spread of viral infection. We found that VGF secreted from early infected cells is cleaved by ADAM10, after which it acts largely in a paracrine manner to direct cell motility at the leading edge of infection. Real-time tracking of cells infected in the presence of EGFR, MAPK, FAK and ADAM10 inhibitors or with VGF-deleted and F11-deleted viruses revealed defects in radial velocity and directional migration efficiency, leading to impaired cell-to-cell spread of infection. Furthermore, intravital imaging showed that virus spread and lesion formation are attenuated in the absence of VGF. Our results demonstrate how poxviruses hijack epidermal growth factor receptor-induced cell motility to promote rapid and efficient spread of infection in vitro and in vivo.

Original languageEnglish
Pages (from-to)216-225
Number of pages10
JournalNature Microbiology
Issue number2
Early online date12 Nov 2018
Publication statusPublished - Feb 2019

ASJC Scopus subject areas

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


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