2. Academic Validation
  3. Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus

Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus

  • Virology. 2016 Oct;497:125-135. doi: 10.1016/j.virol.2016.07.016.
William D Arndt 1,  Stacy D White 2,  Brian P Johnson 3,  Trung Huynh 4,  Jeffrey Liao 5,  Heather Harrington 6,  Samantha Cotsmire 7,  Karen V Kibler 8,  Jeffrey Langland 9,  Bertram L Jacobs 10
Affiliations

Affiliations

  • 1 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: [email protected].
  • 2 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: [email protected].
  • 3 The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: [email protected].
  • 4 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: [email protected].
  • 5 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: [email protected].
  • 6 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: [email protected].
  • 7 The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: [email protected].
  • 8 The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: [email protected].
  • 9 The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address: [email protected].
  • 10 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: [email protected].
PMID: 27467578 DOI: 10.1016/j.virol.2016.07.016
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.

Keywords

E3 gene; F3 gene; IBT resistance; Innate immune evasion; Monkeypox virus; Poxvirus pathogenesis; Poxvirus transcription; Vaccinia virus; Virulence; dsRNA.

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