Ectromelia virus lacking the E3L ortholog is replication-defective and nonpathogenic but does induce protective immunity in a mouse strain susceptible to lethal mousepox

Virology. 2018 May;518:335-348. doi: 10.1016/j.virol.2018.03.016. Epub 2018 Mar 27.


All known orthopoxviruses, including ectromelia virus (ECTV), contain a gene in the E3L family. The protein product of this gene, E3, is a double-stranded RNA-binding protein. It can impact host range and is used by orthopoxviruses to combat cellular defense pathways, such as PKR and RNase L. In this work, we constructed an ECTV mutant with a targeted disruption of the E3L open reading frame (ECTVΔE3L). Infection with this virus resulted in an abortive replication cycle in all cell lines tested. We detected limited transcription of late genes but no significant translation of these mRNAs. Notably, the replication defects of ECTVΔE3L were rescued in human and mouse cells lacking PKR. ECTVΔE3L was nonpathogenic in BALB/c mice, a strain susceptible to lethal mousepox disease. However, infection with ECTVΔE3L induced protective immunity upon subsequent challenge with wild-type virus. In summary, E3L is an essential gene for ECTV.

Keywords: Double-stranded RNA; E3L gene; Ectromelia virus; Host range gene; Innate immune evasion; Mousepox virus; PKR; dsRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Ectromelia virus / genetics
  • Ectromelia virus / immunology*
  • Ectromelia virus / pathogenicity
  • Ectromelia virus / physiology*
  • Ectromelia, Infectious / prevention & control*
  • Gene Knockout Techniques
  • Humans
  • Mice, Inbred BALB C
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*
  • Virus Replication*


  • E3L protein, Ectromelia virus
  • RNA-Binding Proteins
  • Vaccines, Attenuated
  • Viral Proteins
  • Viral Vaccines