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Journal of Virology, December 2009, p. 12279-12289, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.00664-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Transgenic Expression of the 3D Polymerase Inhibits Theiler's Virus Infection and Demyelination{triangledown} ,{dagger}

Jason Kerkvliet,1 Laurie Zoecklein,1 Louisa Papke,1 Aleksandar Denic,1 Allan J. Bieber,1 Larry R. Pease,2 Chella S. David,2 and Moses Rodriguez1,2*

Departments of Neurology,1 Immunology, Mayo Clinic, Rochester, Minnesota 559052

Received 31 March 2009/ Accepted 3 September 2009

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.

* Corresponding author. Mailing address: Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Phone: (507) 284-4663. Fax: (507) 284-1086. E-mail: rodriguez.moses{at}mayo.edu

{triangledown} Published ahead of print on 16 September 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, December 2009, p. 12279-12289, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.00664-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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