Duncan, Melanie LauraHorsington, JacquelynEldi, PreethiAl Rumaih, ZahrahKarupiah, GunasegaranNewsome, Timothy2021-11-152021-11-151999-4915http://hdl.handle.net/1885/251818Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1. Here, we describe the generation of a recombinant ECTV that is specifically disrupted in actin-based motility allowing us to examine the role of this transport step in vivo for the first time. We show that actin-based motility has a critical role in promoting the release of virus from infected cells in vitro but plays a minor role in virus spread in vivo. It is likely that loss of microtubule-dependent transport is a major factor for the attenuation observed when A36R is deleted.This work was funded by the National Health and Medical Research Council through the grants APP100790 (G.K) and GNT0632785 (T.N).application/pdfen-AU© 2018 by the authors. Licensee MDPI, Basel, Switzerland.http://creativecommons.org/licenses/by/4.0/201810.3390/v100301112020-11-23Creative Commons Attribution (CC BY) license