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A Model for Epilepsy of Infectious Etiology using Theiler's Murine Encephalomyelitis Virus
Published on: June 23, 2022
Identification of a novel neuropathogenic Theiler's murine encephalomyelitis virus
Matthew R Buckwalter1, Phan Thi Nga, Meriadeg Ar Gouilh
1Laboratory of Dendritic Cell Immunobiology, Department of Immunology, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, Cedex 15, France.
Abstract:
Theiler's murine encephalitis viruses (TMEV) are divided into two subgroups based on their neurovirulence. Persistent strains resemble Theiler's original viruses (referred to as the TO subgroup), which largely induce a subclinical polioencephalomyelitis during the acute phase of the disease and can persist in the spinal cord of susceptible animals, inducing a chronic demyelinating disease. In contrast, members of the neurovirulent subgroup cause an acute encephalitis characterized by the rapid onset of paralysis and death within days following intracranial inoculation. We report herein the characterization of a novel neurovirulent strain of TMEV, identified using pyrosequencing technology and referred to as NIHE. Complete coverage of the NIHE viral genome was obtained, and it shares <90% nucleotide sequence identity to known TMEV strains irrespective of subgroup, with the greatest sequence variability being observed in genes encoding the leader and capsid proteins. The histopathological analysis of infected brain and spinal cord demonstrate inflammatory lesions and neuronal necrosis during acute infection with no evidence of viral persistence or chronic disease. Intriguingly, genetic analysis indicates the putative expression of the L protein, considered a hallmark of strains within the persistent subgroup. Thus, the identification and characterization of a novel neurovirulent TMEV strain sharing features previously associated with both subgroups will lead to a deeper understanding of the evolution of TMEV strains and new insights into the determinants of neurovirulence.
Insights
A new neurovirulent strain of Theiler's murine encephalitis virus (TMEV), named NIHE, was identified. This strain exhibits unique genetic characteristics and causes acute disease, offering insights into TMEV evolution and neurovirulence.
Area of Science:
- Virology
- Neuroscience
- Molecular Biology
Background:
- Theiler's murine encephalitis virus (TMEV) is classified into persistent (TO subgroup) and neurovirulent subgroups based on disease outcome.
- Persistent TMEV strains cause polioencephalomyelitis and chronic demyelinating disease, while neurovirulent strains induce acute encephalitis and rapid death.
Purpose of the Study:
- To characterize a novel, highly neurovirulent TMEV strain, designated NIHE, identified through pyrosequencing.
- To investigate the genetic makeup and pathogenic features of the NIHE strain and compare it to known TMEV subgroups.
Main Methods:
- Pyrosequencing technology for complete genome coverage of the novel TMEV strain.
- Comparative nucleotide sequence analysis to determine genetic relatedness to known TMEV strains.
- Histopathological examination of infected brain and spinal cord tissues to assess disease manifestations.
Main Results:
- The NIHE strain shares <90% nucleotide sequence identity with known TMEV strains, with significant variability in leader and capsid protein genes.
- Histopathology revealed inflammatory lesions and neuronal necrosis during acute infection, with no signs of viral persistence or chronic disease.
- Genetic analysis suggested the expression of the L protein, typically associated with persistent TMEV strains.
Conclusions:
- The novel NIHE strain represents a unique TMEV variant with neurovirulent properties but also features associated with persistent strains.
- This discovery provides a valuable model for studying TMEV evolution and the molecular determinants of neurovirulence.
- Further research on NIHE can elucidate the mechanisms underlying the dichotomy of TMEV pathogenesis.
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