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.
Sato
S
S
Department of Neurology, University of Chicago Medical Center, Illinois 60637, USA.
Zhang
L
L
Kim
J
J
Jakob
J
J
Grant
R A
RA
Wollmann
R
R
Roos
R P
RP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D002213:Capsid / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D002460:Cell Line; D006224:Cricetinae; D018360:Crystallography, X-Ray; D018985:Epitopes, B-Lymphocyte / Q000032:analysis / Q000276:immunology*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D011051:Poliomyelitis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D011487:Protein Conformation; D013116:Spinal Cord / Q000473:pathology; D017945:Theilovirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D018985:Epitopes, B-Lymphocyte; C442556:VP2 protein, Theilovirus