title: Evasion of the Innate Immune Type I Interferon System by Monkeypox Virus.
abstract: The vaccinia virus (VACV) E3 protein has been shown to be important for blocking activation of the cellular innate immune system and allowing viral replication to occur unhindered. Mutation or deletion of E3L severely affects viral host range and pathogenesis. While the monkeypox virus (MPXV) genome encodes a homologue of the VACV E3 protein, encoded by the F3L gene, the MPXV gene is predicted to encode a protein with a truncation of 37 N-terminal amino acids. VACV with a genome encoding a similarly truncated E3L protein (VACV-E3LΔ37N) has been shown to be attenuated in mouse models, and infection with VACV-E3LΔ37N has been shown to lead to activation of the host antiviral protein kinase R pathway. In this report, we present data demonstrating that, despite containing a truncated E3 homologue, MPXV phenotypically resembles a wild-type (wt) VACV rather than VACV-E3LΔ37N. Thus, MPXV appears to contain a gene or genes that can suppress the phenotypes associated with an N-terminal truncation in E3. The suppression maps to sequences outside F3L, suggesting that the suppression is extragenic in nature. Thus, MPXV appears to have evolved mechanisms to minimize the effects of partial inactivation of its E3 homologue.
  
  
  OBJECTIVE
  Poxviruses have evolved to have many mechanisms to evade host antiviral innate immunity; these mechanisms may allow these viruses to cause disease. Within the family of poxviruses, variola virus (which causes smallpox) is the most pathogenic, while monkeypox virus is intermediate in pathogenicity between vaccinia virus and variola virus. Understanding the mechanisms of monkeypox virus innate immune evasion will help us to understand the evolution of poxvirus innate immune evasion capabilities, providing a better understanding of how poxviruses cause disease.
authors.affiliation: School of Life Sciences, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Arndt
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Cotsmire
authors.affiliation: School of Life Sciences, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Trainor
authors.affiliation: School of Life Sciences, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Harrington
authors.affiliation: School of Life Sciences, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Hauns
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA.
authors.forename: Karen V
authors.initials: KV
authors.lastname: Kibler
authors.affiliation: School of Life Sciences, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA.
authors.forename: Trung P
authors.initials: TP
authors.lastname: Huynh
authors.affiliation: School of Life Sciences, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA bjacobs@asu.edu.
authors.forename: Bertram L
authors.initials: BL
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D006801:Humans; D011817:Rabbits; D000595:Amino Acid Sequence; D005075:Biological Evolution; D002460:Cell Line; D002522:Chlorocebus aethiops; D003412:Cricetulus; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D015870:Gene Expression; D006367:HeLa Cells; D058507:Host Specificity; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D007113:Immunity, Innate; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D008993:Monkeypox virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D015398:Signal Transduction; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014779:Virus Replication; D045908:Mpox, Monkeypox / Q000276:immunology
chemical_list: C081374:E3L protein, Vaccinia virus; D007370:Interferon Type I; D016601:RNA-Binding Proteins; D014764:Viral Proteins