Editors' ChoiceHost-Pathogen Interactions

EGFR signaling moves infection

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Science Signaling  12 Feb 2019:
Vol. 12, Issue 568, eaau2214
DOI: 10.1126/scisignal.aau2214

A viral EGF homolog increases the migration of cells infected with vaccinia virus to promote viral spread.

Virally encoded effector proteins can increase the motility of infected cells to promote viral dissemination. To identify factors that promote the migration of vaccinia virus (VACV) infected cells, Beerli et al. engineered viruses that lacked viral homologs of epidermal growth factor (EGF), which are necessary for cellular proliferation and viral replication in mice. Loss of viral growth factor (VGF) reduced viral plaque size and the motility of infected cells without reducing the production of extracellular enveloped virions or plasma membrane cell–associated virions. In cells infected with VACV lacking VGF, EGFR and its downstream target kinases Raf, MEK, ERK, and FAK were not phosphorylated. Inhibitors of EGFR and its targets also reduced WT VACV plaque size and the motility of infected cells. EGFR stimulation and cell migration required the release of VGF from infected cells by the metalloprotease ADAM10. In mouse ears, lesions caused by infection with VACV lacking VGF were smaller than those caused by infection with VGF-bearing VACV. Together, these results provide new molecular details about how a VACV effector protein stimulates EGFR signaling and promotes cell migration to facilitate viral spread.

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