Related Experiment Video
Updated: Jun 20, 2026
Transient Expression of Proteins by Hydrodynamic Gene Delivery in Mice
Published on: May 5, 2014
Transgenic expression of the 3D polymerase inhibits Theiler's virus infection and demyelination
Jason Kerkvliet1, Laurie Zoecklein, Louisa Papke
1Departments of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Abstract:
The RNA-dependent RNA polymerase 3D(pol) 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-D(b) 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.
Insights
Transgenic expression of RNA-dependent RNA polymerase 3D (3Dpol) significantly reduced Theiler's murine encephalomyelitis virus (TMEV) loads in mice. This viral load reduction protected the central nervous system from damage, preserving motor function.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Picornavirus RNA replication relies on RNA-dependent RNA polymerase 3D (3Dpol).
- Investigating viral gene effects on host immunity is crucial for understanding viral pathogenesis.
Purpose of the Study:
- To evaluate the impact of transgenic 3Dpol expression on viral load and host response to Theiler's murine encephalomyelitis virus (TMEV).
- To explore potential therapeutic strategies targeting picornavirus replication.
Main Methods:
- Transgenic expression of 3Dpol in susceptible (FVB) and resistant (FVB-Db) mice.
- Infection with TMEV to assess viral loads, central nervous system (CNS) damage, and motor function.
- Evaluation in T and B cell-deficient mice (FVB-Rag(-/-).3D) to investigate the role of adaptive immunity.
Main Results:
- Transgenic 3Dpol expression substantially lowered TMEV viral loads in susceptible FVB mice.
- Reduced viral loads correlated with decreased spinal cord damage, preserved axons, and maintained motor function.
- 3Dpol expression also reduced early viral loads in resistant FVB-Db mice and was protective in immunodeficient mice, suggesting a direct antiviral mechanism.
Conclusions:
- Overexpressed 3Dpol directly inhibits picornavirus replication, independent of adaptive immunity.
- This finding offers a novel therapeutic avenue for picornavirus infections.
- Understanding 3Dpol's inhibitory role can inform the development of new antiviral therapies.
