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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.

journal_name

Virology

journal_title

Virology

authors

Brandt T,Heck MC,Vijaysri S,Jentarra GM,Cameron JM,Jacobs BL

doi

10.1016/j.virol.2005.01.006

subject

Has Abstract

pub_date

2005-03-15 00:00:00

pages

263-70

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(05)00012-7

journal_volume

333

pub_type

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