Mapping regions of Env important in the neutralization of equine infectious anemia virus
Talmadge, R. L.
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The development of neutralizing antibody (NAb) is important for the immunological control and clinical quiescence in horses infected with equine infectious anemia virus (EIAV). Over time, however, viral genotypes evolve that resist NAb, resulting in recrudescence of clinical disease. Our long-term goal to develop an effective vaccine for EIAV will be aided by identification of epitopes that facilitate viral immune escape from neutralizing antibody. There are eight variable regions, V1-V8, in the surface envelope glycoprotein (SU) of EIAV. Two neutralizing epitopes recognized by mouse monoclonal antibodies are found in V3, in a region termed the Principal Neutralizing Domain (PND). A third neutralization epitope is found in a conserved region of V5. Studies in our laboratory have shown that variation outside of these regions modify sensitivity to neutralization. In this study we investigated the role of variable regions V5, V6, and V7 in neutralization of EIAV. Six chimeric viruses that differed in V5, V6, and/or V7 sequences were created with the cell culture-adapted EIAV19 and the virulent wild-type EIAVwyo. These viruses were then tested in neutralization assays against a panel of serum collected from horses naturally or experimentally infected with EIAV. Preliminary results indicate the presence of an additional neutralization epitope in the V6 region. In addition, sensitivity to neutralization was modified by variation in V7 that added a potential N-linked glycosylation site. These results indicate that genetic changes outside the PND contribute to antigenic variation and immune escape. Further characterization of these epitopes could enhance design of safe and effective vaccines for EIAV.