title: Attenuation of monkeypox virus by deletion of genomic regions.
abstract: Monkeypox virus (MPXV) is an emerging pathogen from Africa that causes disease similar to smallpox. Two clades with different geographic distributions and virulence have been described. Here, we utilized bioinformatic tools to identify genomic regions in MPXV containing multiple virulence genes and explored their roles in pathogenicity; two selected regions were then deleted singularly or in combination. In vitro and in vivo studies indicated that these regions play a significant role in MPXV replication, tissue spread, and mortality in mice. Interestingly, while deletion of either region led to decreased virulence in mice, one region had no effect on in vitro replication. Deletion of both regions simultaneously also reduced cell culture replication and significantly increased the attenuation in vivo over either single deletion. Attenuated MPXV with genomic deletions present a safe and efficacious tool in the study of MPX pathogenesis and in the identification of genetic factors associated with virulence.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA. Electronic address: loperapena@wisc.edu.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Lopera
authors.affiliation: National Wildlife Health Center, U.S. Geological Survey, Madison, WI, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Falendysz
authors.affiliation: National Wildlife Health Center, U.S. Geological Survey, Madison, WI, USA.
authors.forename: Tonie E
authors.initials: TE
authors.lastname: Rocke
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA. Electronic address: osorio@svm.vetmed.wisc.edu.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Osorio
mesh_terms: D000818:Animals; D000914:Antibodies, Viral; D002460:Cell Line; D005260:Female; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D045908:Mpox, Monkeypox / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D008993:Monkeypox virus / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity; D009154:Mutation; D060888:Real-Time Polymerase Chain Reaction; D016865:Reassortant Viruses; D010948:Viral Plaque Assay; D014774:Virulence; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: D000914:Antibodies, Viral
keywords: In vivo bioluminescence imaging; Monkeypox virus; Monkeypox virus pathogenesis; Vaccinia virus; Variola virus; Viral replication; Virulence factors