title: Recombinant myxoma virus lacking all poxvirus ankyrin-repeat proteins stimulates multiple cellular anti-viral pathways and exhibits a severe decrease in virulence.
abstract: Although the production of single gene knockout viruses is a useful strategy to study viral gene functions, the redundancy of many host interactive genes within a complex viral genome can obscure their collective functions. In this study, a rabbit-specific poxvirus, myxoma virus (MYXV), was genetically altered to disrupt multiple members of the poxviral ankyrin-repeat (ANK-R) protein superfamily, M-T5, M148, M149 and M150. A particularly robust activation of the NF-κB pathway was observed in A549 cells following infection with the complete ANK-R knockout (vMyx-ANKsKO). Also, an increased release of IL-6 was only observed upon infection with vMyx-ANKsKO. In virus-infected rabbit studies, vMyx-ANKsKO was the most extensively attenuated and produced the smallest primary lesion of all ANK-R mutant constructs. This study provides the first insights into the shared functions of the poxviral ANK-R protein superfamily in vitro and in vivo.
authors: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100266, Gainesville FL 32610, USA.
authors: Stephanie A
authors: SA
authors: Lamb
authors: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100266, Gainesville FL 32610, USA.
authors: Masmudur M
authors: MM
authors: Rahman
authors: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100266, Gainesville FL 32610, USA.
authors: Grant
authors: G
authors: McFadden
mesh_terms: D000818:Animals; D017089:Ankyrin Repeat; D017353:Gene Deletion; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D009233:Myxoma virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D011213:Poxviridae Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D011817:Rabbits / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D014764:Viral Proteins
keywords: Ankyrin-repeat; Interleukin 6; M-T5; M148; M149; M150; Myxoma virus; Myxomatosis; Nuclear factor kappa B; Poxvirus