Theiler's virus persists in glial cells during demyelinating disease

Area of Science:

• Neurovirology
• Immunology
• Pathogenesis

Background:

• Theiler's murine encephalomyelitis virus (T-MuEV) induces a persistent, demyelinating central nervous system (CNS) disease in mice.
• Understanding the cellular tropism and persistence mechanisms of T-MuEV is crucial for developing therapeutic strategies.

Purpose of the Study:

• To investigate the cellular localization and temporal dynamics of T-MuEV RNA during acute and demyelinating phases of infection in mice.
• To elucidate the role of neurons and glial cells in the persistence of T-MuEV within the CNS.

Main Methods:

• In situ hybridization was employed to detect T-MuEV RNA in histological sections of the brain and spinal cord of experimentally infected mice.
• Quantitative and qualitative assessments of viral RNA distribution in different cell types (neurons and glial cells) were performed.

Main Results:

• Viral RNA was detected in both neurons and glial cells during the early acute phase, with significantly higher levels in neurons.
• During the late demyelinating phase, viral RNA was predominantly found in low amounts within glial cells in the spinal cord white matter.
• No viral RNA was detected in neurons during the late demyelinating phase.

Conclusions:

• T-MuEV demonstrates a distinct cellular tropism shift during persistent infection, with glial cells serving as the primary reservoir.
• The differential replication and persistence in neurons versus glial cells inform a proposed model for T-MuEV pathogenesis.
• These findings highlight the importance of targeting glial cells for managing persistent T-MuEV infections.