A neutralization site of DA strain of Theiler's murine encephalomyelitis virus important for disease phenotype.

DA strain of TMEV induces a chronic, persistent, demyelinating disease in SJL/J weanling mice, while inoculation with GDVII strain of TMEV induces an acute, lethal neurovirulent disease. We show that three amino acids in the DA EF loop-DAV P2 141 Lys, 143 Gly, and 173 Thr-are part of a neutralization site of DA monoclonal antibody (mAb), DAmAb1. DA virus with a mutation of VP2 143 from Gly to Asp, like wild-type virus, persists 6 weeks postinfection (PI) and produces white matter disease. DA virus with a mutation of VP2 141 from Lys to Asn persists but does not induce significant white matter disease. DA virus with a mutation of DA VP2 173 from Thr to Phe fails to persist or to induce significant white matter disease. The diversity and complexity of the mutant virus-induced disease phenotype presumably reflects the varied effects of the mutated amino acid residues on the three-dimensional structure of the viral capsid. The localization of DA VP2 141 and VP2 173 near the putative receptor binding region of the virus suggest that a disruption of interactions between the virus and its receptor is important in the late demyelinating disease and for virus neutralization.