Vaccinia virus dissemination relies on the recruitment of the nucleation promoting factor N-WASP underneath cell-associated extracellular virus (CEVs) and subsequent recruitment and activation of the ARP2/3 complex, a major actin nucleator of the host cell. We have recently discovered that, in addition to the N-WASP/ARP2/3 pathway, vaccinia actin-based motility also relies on the small GTPase Rac1 and its downstream effector the formin-type actin nucleator FHOD1. Here we discuss the potential signaling mechanisms supporting the integration of the N-WASP/ARP2/3 and Rac1/FHOD1 pathways. We suggest the existence of a receptor tyrosine kinase family member that would integrate the Src-dependent activation of the N-WASP/ARP2/3 pathway and the GTP exchange factor-dependent activation of the Rac1/FHOD1 pathway.
Keywords: ARP2/3 complex; Dissemination; FHOD1; N-WASP; Rac1; actin-based motility; spread from cell to cell; vaccinia.