A SPONTANEOUS LOW-PATHOGENIC VARIANT OF THEILERS VIRUS CONTAINS AN AMINO-ACID SUBSTITUTION WITHIN THE PREDOMINANT VP1(233-250) T-CELL EPITOPE

Theiler's murine encephalomyelitis virus (TMEV) induces immune-mediate d demyelination after intracerebral inoculation of the virus into susc eptible mouse strains, We isolated from a TMEV BeAn 8386 viral stock, a low-pathogenic variant which requires greater than a 10,000-fold inc rease in viral inoculation for the manifestation of detectable clinica l signs, Intracerebral inoculation of this variant virus induced a str ong, long-lasting, protective immunity from the demyelinating disease caused by pathogenic TMEV. The levels of antibodies to the whole virus as well as to the major linear epitopes were similar in mice infected with either the variant or wild-type virus. However, persistence of t he variant virus in the central nervous system (CNS) of mice was signi ficantly lower than that of the pathogenic virus. In addition the T-ce ll response to the predominant VP1 (VP1(233-250)) epitope in mice infe cted with the variant virus was significantly weaker than that in mice infected with the parent virus, while similar T-cell responses were i nduced against another predominant epitope (VP2(74-86)). Further analy ses indicated that a change of lysine to arginine at position 244 of V P1, which is the only amino acid difference in the P1 region, is respo nsible for such differential T-cell recognition. Thus, the difference in the T-cell reactivity to this VP1 region as well as the low level o f viral persistence in the CNS may account for the low pathogenicity o f this spontaneous, variant virus.