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

B. Billings, S. A. Smith, Z. Zhang, Debomoy Lahiri, Girish J. Kotwal

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)297-302
Number of pages6
JournalAnnals of the New York Academy of Sciences
Volume1030
DOIs
StatePublished - 2004

Fingerprint

Vaccinia virus
Virus Replication
Viruses
Gene expression
Brain
Gene Expression
Open Reading Frames
Proteins
Vaccines
Tissue
Encephalitis
Histology
Nitric Oxide Synthase
Neutrophils
Virus
Replication
Mouse
Growth
Protein

Keywords

  • Gene deletion
  • Vaccination
  • Vaccinia virus
  • Virulence gene

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lack of N1L gene expression results in a significant decrease of vaccinia virus replication in mouse brain. / Billings, B.; Smith, S. A.; Zhang, Z.; Lahiri, Debomoy; Kotwal, Girish J.

In: Annals of the New York Academy of Sciences, Vol. 1030, 2004, p. 297-302.

Research output: Contribution to journalArticle

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