The role of myelin in Theiler's virus persistence in the central nervous system

Area of Science:

• Neurovirology
• Demyelinating Diseases
• Picornaviruses

Background:

• Theiler's virus (TMEV) causes persistent central nervous system (CNS) infection in mice, modeling multiple sclerosis.
• TMEV initially infects neurons but persists in glial cells, including oligodendrocytes and macrophages.
• Mechanisms of TMEV spread from neurons to glial cells and the roles of oligodendrocytes and macrophages in persistence remain unclear.

Purpose of the Study:

• To investigate the role of myelin in Theiler's virus persistence.
• To understand the mechanism of TMEV trafficking from neurons to glial cells.
• To elucidate the contribution of oligodendrocytes and macrophages to viral persistence.

Main Methods:

• Utilized the shiverer mouse model, which lacks myelin basic protein (MBP).
• Employed immune chimeras to assess the roles of immune responses and cell recruitment.
• Conducted in vivo and in vitro experiments to evaluate viral permissiveness in different cell types.
• Examined viral antigen localization in wild-type and mutant mice using the optic nerve as a model.

Main Results:

• Shiverer mice are resistant to persistent TMEV infection, independent of immune responses.
• The shiverer mutation does not affect the permissiveness of neurons, oligodendrocytes, or macrophages to TMEV.
• Viral antigens are found within myelin cytoplasmic channels during persistent infection in wild-type mice.
• TMEV demonstrates axon-to-myelin trafficking from retinal ganglion cell axons, a process impaired in shiverer mice.

Conclusions:

• Uncovered a novel axon-to-myelin trafficking pathway for Theiler's virus.
• Demonstrated the essential role of myelin/oligodendrocyte infection in Theiler's virus persistence.
• Highlighted the shiverer mutation's impairment of this critical viral trafficking route.