MOLECULAR PATHOGENESIS OF THEILERS MURINE ENCEPHALOMYELITIS VIRUS-INDUCED DEMYELINATING DISEASE IN MICE

After an acute phase of virus growth in neurons (e.g. anterior horn ce lls), Theiler's murine encephalomyelitis virus (TMEV) persists as a ch ronic productive infection, largely in macrophages in the CNS white ma tter. TMEV replication in macrophages is highly restricted, probably a s the result of host cell factors. The preponderance of evidence indic ates that TMEV persistence leads to immunopathologic damage of myelin, mediated by major histocompatibility class II-restricted Th1 lymphocy tes directed at a virus epitope(s) rather than host neuroantigens at l east early in the infection. Analysis of TMEV recombinant and mutant v iruses suggests that persistence requires a specific capsid conformati on involving the VP2 puff and VP1 loops, which may influence persisten ce through virion receptor binding or attachment to host cells, e.g. m acrophages.