Abstract
Ectromelia 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.
Highlights
Ectromelia virus (ECTV) is an orthopoxvirus endemic to mice that has been used extensively as a model for variola virus, the causative agent of smallpox [1]
The A36R gene was deleted in ECTV-Mos by replacing the gene with
Actin nucleation has been demonstrated for VACV, ECTV, variola and monkeypox viruses induced actin nucleation has been demonstrated for VACV, ECTV, variola and monkeypox
Summary
Ectromelia virus (ECTV) is an orthopoxvirus endemic to mice that has been used extensively as a model for variola virus, the causative agent of smallpox [1]. In common with other orthopoxviruses, ECTV is among a select group of bacterial and viral pathogens able to harness actin-nucleating activity at the pathogen surface to promote their spread [2,3,4]. The contribution of actin-based motility to disease progression is difficult to assess in these complex systems due to the pleiotropy of pathogen-encoded activators of actin polymerization and the lack of availability of in vivo experimental models that faithfully reproduce endogenous infections. Actin-based motility is conserved in the orthopoxvirus genus including variola virus, monkeypox virus, ECTV [5]
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