title: Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus.
abstract: Monkeypox virus (MPXV) infection fails to activate the host anti-viral protein, PKR, despite lacking a full-length homologue of the vaccinia virus (VACV) PKR inhibitor, E3. Since PKR can be activated by dsRNA produced during a viral infection, we have analyzed the accumulation of dsRNA in MPXV-infected cells. MPXV infection led to less accumulation of dsRNA than VACV infection. Because in VACV infections accumulation of abnormally low amounts of dsRNA is associated with mutations that lead to resistance to the anti-poxvirus drug isatin beta-thiosemicarbazone (IBT), we investigated the effects of treatment of MPXV-infected cells with IBT. MPXV infection was eight-fold more resistant to IBT than wild-type vaccinia virus (wtVACV). These results demonstrate that MPXV infection leads to the accumulation of less dsRNA than wtVACV, which in turn likely leads to a decreased capacity for activation of the dsRNA-dependent host enzyme, PKR.
authors.affiliation: School of Life Sciences, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA; The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: wdarndt@sandia.gov.
authors.forename: William D
authors.initials: WD
authors.lastname: Arndt
authors.affiliation: School of Life Sciences, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA; The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: Stacy.White@azdhs.gov.
authors.forename: Stacy D
authors.initials: SD
authors.lastname: White
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: brian.p.johnson@asu.edu.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Johnson
authors.affiliation: School of Life Sciences, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA; The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: trung.huynh@asu.edu.
authors.forename: Trung
authors.initials: T
authors.lastname: Huynh
authors.affiliation: School of Life Sciences, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA; The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: Jeffrey.liao@asu.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Liao
authors.affiliation: School of Life Sciences, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA; The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: heather.harrington@asu.edu.
authors.forename: Heather
authors.initials: H
authors.lastname: Harrington
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: Samantha.cotsmire@asu.edu.
authors.forename: Samantha
authors.initials: S
authors.lastname: Cotsmire
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: Karen.kibler@asu.edu.
authors.forename: Karen V
authors.initials: KV
authors.lastname: Kibler
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: jeffrey.langland@asu.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Langland
authors.affiliation: School of Life Sciences, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA; The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: bjacobs@asu.edu.
authors.forename: Bertram L
authors.initials: BL
authors.lastname: Jacobs
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004279:DNA, Viral; D024882:Drug Resistance, Viral; D006367:HeLa Cells; D006801:Humans; D008993:Monkeypox virus / Q000187:drug effects* / Q000502:physiology*; D016366:Open Reading Frames; D012330:RNA, Double-Stranded / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014616:Vaccinia virus / Q000187:drug effects* / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D012330:RNA, Double-Stranded; D014764:Viral Proteins
keywords: E3 gene; F3 gene; IBT resistance; Innate immune evasion; Monkeypox virus; Poxvirus pathogenesis; Poxvirus transcription; Vaccinia virus; Virulence; dsRNA