The genetics of the persistent infection and demyelinating disease caused by Theiler's virus

Area of Science:

• Neurovirology
• Immunology
• Demyelinating diseases

Background:

• Theiler's virus (TMEV) is a model for persistent, demyelinating central nervous system (CNS) infections.
• TMEV infection in mice mimics aspects of multiple sclerosis.
• Understanding TMEV persistence mechanisms is key to developing therapeutic strategies.

Purpose of the Study:

• To review the mechanisms underlying Theiler's virus persistence in the mouse CNS.
• To explore viral factors and host responses contributing to chronic infection.
• To highlight the role of glial cells and immune cells in viral persistence.

Main Methods:

• Review of existing literature on Theiler's virus pathogenesis and persistence.
• Analysis of viral protein functions (L and L*) in host immune evasion.
• Examination of host genetic factors influencing susceptibility to persistent infection.

Main Results:

• TMEV initially infects neurons, then establishes persistent infection in glial cells and macrophages.
• Viral protein L restricts interferon production, while L* aids macrophage infection.
• Host susceptibility is multigenic, with H2 class I genes and Tmevp3 playing significant roles.

Conclusions:

• Viral proteins L and L* are critical for TMEV persistence by evading host defenses.
• Oligodendrocytes are essential host cells, and myelin mutations confer resistance.
• Genetic factors in mice significantly influence susceptibility to persistent TMEV infection.