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Neutralizing monoclonal antibodies to Theiler's murine encephalomyelitis viruses
Abstract:
Theiler's murine encephalomyelitis viruses (TMEV) are serologically related picornaviruses which cause both enteric and neurological disease in mice. The biological activities of TMEV vary between the two different TMEV subgroups (TO and GDVII) and with different passage histories of the same TMEV strain (e.g., mouse brain-passed versus tissue culture-passed DA strain of the TO subgroup). We raised neutralizing monoclonal antibodies (mAbs) against tissue culture-passed DA and GDVII strains of TMEV. We produced two mAbs against the DA strain which neutralized all members of the TO subgroup, but not the GDVII subgroup strains (GDVII and FA); these two DA mAbs reacted similarly with both mouse brain-passed DA and tissue culture-passed DA. Of six neutralizing GDVII mAbs, four reacted only to GDVII and FA, whereas two neutralized TO strains as well. These mAbs demonstrate the presence of TMEV group-specific as well as subgroup-specific neutralization and substantiate the division of TMEV into two distinct subgroups. On Western immunoblots one of the two DA mAbs reacted against isolated DA VP1, two GDVII mAbs (which were TMEV group specific) reacted against isolated GDVII VP1 and DA VP1, and the other DA mAb and four other GDVII mAbs required an intact virion conformation for reactivity. An analysis of the epitopes recognized by these mAbs may elucidate sites important in TMEV biological activities.
Insights
Monoclonal antibodies reveal distinct neutralization patterns for Theiler's murine encephalomyelitis virus (TMEV) subgroups. This confirms the division of TMEV into TO and GDVII groups, aiding in understanding viral activity.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Theiler's murine encephalomyelitis viruses (TMEV) are picornaviruses causing enteric and neurological diseases in mice.
- TMEV exhibits variable biological activities influenced by subgroups (TO and GDVII) and passage history (e.g., mouse brain vs. tissue culture).
Purpose of the Study:
- To generate and characterize neutralizing monoclonal antibodies (mAbs) against TMEV.
- To investigate TMEV antigenic diversity and subgroup-specific neutralization epitopes.
Main Methods:
- Production of neutralizing monoclonal antibodies against tissue culture-passaged TMEV strains (DA and GDVII).
- Neutralization assays to determine antibody reactivity against different TMEV subgroups and strains.
- Western immunoblot analysis using isolated viral proteins (VP1) and intact virions.
Main Results:
- Two mAbs against the DA strain neutralized all TO subgroup members but not GDVII strains, indicating TO-specific neutralization.
- Six GDVII mAbs showed varied reactivity: four were GDVII/FA-specific, while two neutralized both TO and GDVII strains (group-specific).
- Epitope mapping revealed both TMEV group-specific and subgroup-specific neutralization sites, with some mAbs requiring intact virions.
Conclusions:
- The generated mAbs confirm the existence of TMEV group-specific and subgroup-specific neutralization epitopes.
- These findings substantiate the division of TMEV into two distinct serological subgroups (TO and GDVII).
- Further epitope analysis may elucidate key sites involved in TMEV biological activities and pathogenesis.