The N-terminal domain of the vaccinia virus E3L-protein is required for neurovirulence, but not induction of a protective immune response

Teresa Brandt, Michael C. Heck, Sangeetha Vijaysri, Garilyn M. Jentarra, Jason M. Cameron, Bertram Jacobs

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Encephalitis is a rare, but serious complication from vaccination against smallpox using replication competent strains of vaccinia virus. In this report we describe mutants of vaccinia virus, containing N-terminal deletions of the vaccinia virus interferon resistance gene, E3L, that are attenuated for neuropathogenesis in a mouse model system. These recombinant viruses replicated to high titers in the nasal mucosa after intra-nasal infection of C57BL/6 mice but failed to spread to the lungs or brain. These viruses demonstrated reduced pathogenicity after intra-cranial infection as well, indicating a decrease in neurovirulence. Intra-nasal inoculation or inoculation by scarification with a low dose of recombinant virus containing a deletion of the entire N-terminal domain of E3L protected against challenge with a high dose of wild-type vaccinia virus, suggesting that this replication competent, but attenuated strain of vaccinia virus may have promise as an improved vaccine for protecting against smallpox, and as a vector for inducing mucosal immunity to heterologous pathogenic organisms.

Original languageEnglish (US)
Pages (from-to)263-270
Number of pages8
JournalVirology
Volume333
Issue number2
DOIs
StatePublished - Mar 15 2005

Keywords

  • N-terminal
  • Neurovirulence
  • Vaccinia virus

ASJC Scopus subject areas

  • Virology

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