Distinct cell death mechanisms by Theiler's murine encephalomyelitis virus (TMEV) infection in microglia and macrophage
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Updated: Sep 30, 2026
A Model for Epilepsy of Infectious Etiology using Theiler's Murine Encephalomyelitis Virus
Published on: June 23, 2022
Yoshiro Ohara1, Toshiki Himeda, Kunihiko Asakura
1Department of Microbiology, Kanazawa Medical University, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan. ohara@kanazawa-med.ac.jp
Abstract:
DA strain of Theiler's murine encephalomyelitis virus (TMEV) persists in the mouse central nervous system (CNS) and induces demyelination while GDVII strain fails to persist or demyelinate. L* protein, which is synthesized only in DA but not GDVII, is believed important in virus persistence and demyelination. Because a major reservoir for DA persistence is infiltrated macrophages or microglia, a resident macrophage of the CNS, we investigated TMEV infection of Ra2 cells, a murine microglial cell line. We found that DA strain grew well in Ra2 cells, but not GDVII strain or DAL*-1 virus (which fails to synthesize L* protein), suggesting that L* protein plays an important role in virus growth in microglia. Interestingly, in contrast to virus growth, most Ra2 cells infected with DA strain survived with no evidence of virus-induced apoptosis. These results may be important in clarifying the pathogenesis of DA-induced demyelinating disease.
Insights
The L* protein is crucial for Theiler's murine encephalomyelitis virus (TMEV) DA strain's growth in microglia, contributing to viral persistence and demyelination in the central nervous system (CNS). This protein influences viral replication without causing cell death.
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Theiler's murine encephalomyelitis virus (TMEV) DA strain causes persistent central nervous system (CNS) infection and demyelination.
- The GDVII strain of TMEV does not persist or cause demyelination.
- The viral L* protein, produced by the DA strain but not GDVII, is implicated in TMEV persistence and demyelination.
Purpose of the Study:
- To investigate the role of the L* protein in TMEV replication within microglia.
- To understand the interaction between TMEV strains and microglial cells, the resident macrophages of the CNS.
Main Methods:
- Infection of Ra2 murine microglial cells with TMEV DA strain, GDVII strain, and a mutant virus lacking L* protein (DAL*-1).
- Assessment of viral growth and cell survival post-infection.
Main Results:
- The TMEV DA strain replicated efficiently in Ra2 microglial cells.
- The GDVII strain and the DAL*-1 mutant showed poor replication in Ra2 cells.
- Microglia infected with the DA strain survived without significant apoptosis, despite robust viral growth.
Conclusions:
- The L* protein is essential for TMEV DA strain replication in microglia.
- Microglial survival during TMEV DA infection may contribute to viral persistence in the CNS.
- These findings offer insights into the pathogenesis of TMEV-induced demyelinating disease.
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