Attenuation of a vaccine strain of vaccinia virus via inactivation of interferon viroceptor

B. Dénes, Daila S. Gridley, Nadja Fodor, Zsuzsanna Takátsy, Tatyana M. Timiryasova, István Fodor

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Interferons (IFNs) play an important role in host antiviral responses, but viruses, including vaccinia viruses (VV), employ mechanisms to disrupt IFN activities, and these viral mechanisms are often associated with their virulence. Here, we explore an attenuation strategy with a vaccine strain of VV lacking a virus-encoded IFN-γ receptor homolog (viroceptor). Methods: To facilitate the monitoring of virus properties, first we constructed a Lister vaccine strain derivative VV-RG expressing optical reporters. Further, we constructed a VV-RG derivative, VV-RG8, which lacks the IFN-γR viroceptor (B8R gene product). Replication, immunological and pathogenic properties of the constructed strains were compared. Results: Viruses did not show significant differences in humoral and cellular immune responses of immune-competent mice. Replication of constructed viruses was efficient both in vitro and in vivo, but showed marked difference in kinetics of propagation. In cultured CV-1 epithelial cells, the VV-RG8 strain retained the propagation potential of the parental virus, while, in the C6 glial cells, significant delay was observed in the kinetics of the VV-RG8 replication cycle compared to VV-RG. The pathogenesis of the viruses was tested by survival assay and biodistribution in nude mice. High dose inoculation of nude mice with VV-RG8 caused less pronounced virus dissemination, improved weight gain, and increased survival rate, as compared with the VV-RG strain. Conclusions: The replication-competent virus VV-RG8 carrying a mutation at the B8R gene is less pathogenic for mice than the parental vaccine virus. We anticipate that step-wise inactivation of VV vaccine genes involved in evasion of host immune response may provide an alternative approach for generation of hyper-attenuated replication-competent vaccines.

Original languageEnglish
Pages (from-to)814-823
Number of pages10
JournalJournal of Gene Medicine
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 2006

Fingerprint

Virus Inactivation
Vaccinia virus
Interferons
Vaccines
Viruses
Virus Replication
Nude Mice
Interferon Receptors
Genes
Immune Evasion
Humoral Immunity
Cellular Immunity
Neuroglia
Weight Gain
Antiviral Agents
Virulence

Keywords

  • Imaging
  • Interferon
  • Lister
  • Mutant
  • Optical reporter
  • Vaccine
  • Vaccinia virus
  • Virulence

ASJC Scopus subject areas

  • Genetics

Cite this

Attenuation of a vaccine strain of vaccinia virus via inactivation of interferon viroceptor. / Dénes, B.; Gridley, Daila S.; Fodor, Nadja; Takátsy, Zsuzsanna; Timiryasova, Tatyana M.; Fodor, István.

In: Journal of Gene Medicine, Vol. 8, No. 7, 07.2006, p. 814-823.

Research output: Contribution to journalArticle

Dénes, B, Gridley, DS, Fodor, N, Takátsy, Z, Timiryasova, TM & Fodor, I 2006, 'Attenuation of a vaccine strain of vaccinia virus via inactivation of interferon viroceptor', Journal of Gene Medicine, vol. 8, no. 7, pp. 814-823. https://doi.org/10.1002/jgm.907
Dénes, B. ; Gridley, Daila S. ; Fodor, Nadja ; Takátsy, Zsuzsanna ; Timiryasova, Tatyana M. ; Fodor, István. / Attenuation of a vaccine strain of vaccinia virus via inactivation of interferon viroceptor. In: Journal of Gene Medicine. 2006 ; Vol. 8, No. 7. pp. 814-823.
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AU - Fodor, István

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