Transgenic expression of the 3D polymerase inhibits Theiler's virus infection and demyelination

Jason Kerkvliet, Laurie Zoecklein, Louisa Papke, Aleksandar Denic, Allan J. Bieber, Larry R Pease, Chella S. David, Moses Rodriguez

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The RNA-dependent RNA polymerase 3Dpol is required for the elongation of positive- and negative-stranded picornavirus RNA. During the course of investigating the effect of the transgenic expression of viral genes on the host immune response, we evaluated the viral load present in the host after infection. To our surprise, we found that 3D transgenic expression in genetically susceptible FVB mice led to substantially lower viral loads after infection with Theiler's murine encephalomyelitis virus (TMEV). As a result, spinal cord damage caused by chronic viral infection in the central nervous system was reduced in FVB mice that expressed 3D. This led to the preservation of large-diameter axons and motor function in these mice. The 3D transgene also lowered early viral loads when expressed in FVB-Db mice resistant to persistent TMEV infection. The protective effect of 3D transgenic expression was not altered in FVB-Rag-/-.3D mice that are deficient in T and B cells, thus ruling out a mechanism by which the overexpression of 3D enhanced the adaptive immune clearance of the virus. Understanding how endogenously overexpressed 3D polymerase inhibits viral replication may lead to new strategies for targeting therapies to all picornaviruses.

Original languageEnglish (US)
Pages (from-to)12279-12289
Number of pages11
JournalJournal of Virology
Volume83
Issue number23
DOIs
StatePublished - Dec 2009

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Theilovirus
Demyelinating Diseases
Virus Diseases
gene expression
viruses
viral load
Viral Load
Picornaviridae
mice
infection
RNA-directed RNA polymerase
Central Nervous System Viral Diseases
RNA Replicase
Viral Genes
virus replication
Infection
Transgenes
axons
spinal cord
transgenes

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Transgenic expression of the 3D polymerase inhibits Theiler's virus infection and demyelination. / Kerkvliet, Jason; Zoecklein, Laurie; Papke, Louisa; Denic, Aleksandar; Bieber, Allan J.; Pease, Larry R; David, Chella S.; Rodriguez, Moses.

In: Journal of Virology, Vol. 83, No. 23, 12.2009, p. 12279-12289.

Research output: Contribution to journalArticle

Kerkvliet, J, Zoecklein, L, Papke, L, Denic, A, Bieber, AJ, Pease, LR, David, CS & Rodriguez, M 2009, 'Transgenic expression of the 3D polymerase inhibits Theiler's virus infection and demyelination', Journal of Virology, vol. 83, no. 23, pp. 12279-12289. https://doi.org/10.1128/JVI.00664-09
Kerkvliet, Jason ; Zoecklein, Laurie ; Papke, Louisa ; Denic, Aleksandar ; Bieber, Allan J. ; Pease, Larry R ; David, Chella S. ; Rodriguez, Moses. / Transgenic expression of the 3D polymerase inhibits Theiler's virus infection and demyelination. In: Journal of Virology. 2009 ; Vol. 83, No. 23. pp. 12279-12289.
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