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

William D. Arndt, Stacy D. White, Brian P. Johnson, Trung Huynh, Jeffrey Liao, Heather Harrington, Samantha Cotsmire, Karen Kibler, Jeffrey Langland, Bertram Jacobs

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)125-135
Number of pages11
JournalVirology
Volume497
DOIs
StatePublished - Oct 1 2016

Fingerprint

Monkeypox virus
Poxviridae
Vaccinia virus
Virus Diseases
Pharmaceutical Preparations
Viral Proteins
isatin beta-thiosemicarbazone
Mutation

Keywords

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

ASJC Scopus subject areas

  • Virology

Cite this

Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus. / Arndt, William D.; White, Stacy D.; Johnson, Brian P.; Huynh, Trung; Liao, Jeffrey; Harrington, Heather; Cotsmire, Samantha; Kibler, Karen; Langland, Jeffrey; Jacobs, Bertram.

In: Virology, Vol. 497, 01.10.2016, p. 125-135.

Research output: Contribution to journalArticle

Arndt, William D. ; White, Stacy D. ; Johnson, Brian P. ; Huynh, Trung ; Liao, Jeffrey ; Harrington, Heather ; Cotsmire, Samantha ; Kibler, Karen ; Langland, Jeffrey ; Jacobs, Bertram. / Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus. In: Virology. 2016 ; Vol. 497. pp. 125-135.
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