title: Modulation of the myxoma virus plaque phenotype by vaccinia virus protein F11.
abstract: Vaccinia virus (VACV) produces large plaques consisting of a rapidly expanding ring of infected cells surrounding a lytic core, whereas myxoma virus (MYXV) produces small plaques that resemble a focus of transformed cells. This is odd, because bioinformatics suggests that MYXV carries homologs of nearly all of the genes regulating Orthopoxvirus attachment, entry, and exit. So why does MYXV produce foci? One notable difference is that MYXV-infected cells produce few of the actin microfilaments that promote VACV exit and spread. This suggested that although MYXV carries homologs of the required genes (A33R, A34R, A36R, and B5R), they are dysfunctional. To test this, we produced MYXV recombinants expressing these genes, but we could not enhance actin projectile formation even in cells expressing all four VACV proteins. Another notable difference between these viruses is that MYXV lacks a homolog of the F11L gene. F11 inhibits the RhoA-mDia signaling that maintains the integrity of the cortical actin layer. We constructed an MYXV strain encoding F11L and observed that, unlike wild-type MYXV, the recombinant virus disrupted actin stress fibers and produced plaques up to 4-fold larger than those of controls, and these plaques expanded ∼6-fold faster. These viruses also grew to higher titers in multistep growth conditions, produced higher levels of actin projectiles, and promoted infected cell movement, although neither process was to the extent of that observed in VACV-infected cells. Thus, one reason for why MYXV produces small plaques is that it cannot spread via actin filaments, although the reason for this deficiency remains obscure. A second reason is that leporipoxviruses lack vaccinia's capacity to disrupt cortical actin.
authors.affiliation: Department of Medical Microbiology & Immunology, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Canada.
authors.forename: Chad R
authors.initials: CR
authors.lastname: Irwin
authors.forename: David H
authors.initials: DH
authors.lastname: Evans
mesh_terms: D000818:Animals; D009233:Myxoma virus / Q000235:genetics* / Q000254:growth & development*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D022502:Stress Fibers / Q000378:metabolism; D019562:Viral Load; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C533030:F11L protein, vaccinia virus; D011994:Recombinant Proteins; D014764:Viral Proteins