Lack of N1L gene expression results in a significant decrease of vaccinia virus replication in mouse brain.

Abstract:

:Vaccinia virus encodes secretory proteins termed virokines. One of the major virokines encoded by the N1L open reading frame is the 13.8 kDa protein. A recombinant virus, termed vGK5, lacking this protein when injected intracranially into mice, has one of the highest levels of in vivo attenuation achieved by deletion of any single open reading frame of vaccinia virus. Here we show that the 13.8 kDa protein significantly enhances viral replication within brain tissue; however, analysis of histology, neutrophil infiltrate, and nitric oxide synthase activity of brain tissue shows no significant differences between wild-type vaccinia virus and vGK5. Since there is poor growth of vGK5 virus in the brain, the possibility of postvaccinial encephalitis is significantly diminished. Mice injected with vGK5 became resistant to the lethal effects of vaccinia virus, indicating that vGK5 is immunogenic in the brain without being virulent and therefore is a vaccine candidate. This suggests that should vGK5 reach the brain it will not replicate efficiently but still serve as a live vaccine.

journal_name

Ann N Y Acad Sci

authors

Billings B,Smith SA,Zhang Z,Lahiri DK,Kotwal GJ

doi

10.1196/annals.1329.037

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

297-302

eissn

0077-8923

issn

1749-6632

pii

1030/1/297

journal_volume

1030

pub_type

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