Virological and pathological processes involved in Theiler's virus infection of the central nervous system

Theiler's virus strains GDVII and FA cause an acute encephalitis when injected intracerebrally into mice, whereas strains To, BeAn and DA establish a persistent infection and produce a chronic demyelinating disease. The chronic infection is also dependent on the mouse strain used, with susceptibility linked in part to the D locus of the MHC. The region of the virus genome associated with neurovirulence maps to the P1 region, encoding the capsid proteins, and to the 5′ non-coding region. There is evidence that BeAnDA virus persists in oligodendrocytes, where it reactivates to initiate demyelinating disease. Host factors are involved in the development of the lesion, including CD4(+) T cell responses. These lymphocytes most probably mediate damage through activation of macrophages leading to local destruction of glial cells. Another possible pathological role for the immune system is the recognition of nerve cell antigens and the initiation of autoimmune disease. Such a virus-triggered phenomenon may well underlie human CNS diseases such as multiple sclerosis.