title: The N-terminal domain of the vaccinia virus E3L-protein is required for neurovirulence, but not induction of a protective immune response.
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.
authors.affiliation: Graduate Program in Molecular and Cellular Biology, School of Life Sciences/The Biodesign Institute, Arizona State University Box 874501 Tempe, AZ 85287-4501, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Brandt
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heck
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Vijaysri
authors.forename: Garilyn M
authors.initials: GM
authors.lastname: Jentarra
authors.forename: Jason M
authors.initials: JM
authors.lastname: Cameron
authors.forename: Bertram L
authors.initials: BL
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D005260:Female; D005814:Genes, Viral; D018928:Immunity, Mucosal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D017384:Sequence Deletion; D014615:Vaccinia / Q000209:etiology / Q000276:immunology / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014774:Virulence; D014779:Virus Replication
chemical_list: C081374:E3L protein, Vaccinia virus; D016601:RNA-Binding Proteins; D014764:Viral Proteins