The N-terminal domain of the vaccinia virus E3L-protein is required for neurovirulence, but not induction of a protective immune response.
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.
Brandt
Teresa
T
Graduate Program in Molecular and Cellular Biology, School of Life Sciences/The Biodesign Institute, Arizona State University Box 874501 Tempe, AZ 85287-4501, USA.
Heck
Michael C
MC
Vijaysri
Sangeetha
S
Jentarra
Garilyn M
GM
Cameron
Jason M
JM
Jacobs
Bertram L
BL
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
C081374:E3L protein, Vaccinia virus; D016601:RNA-Binding Proteins; D014764:Viral Proteins