A detailed mutagenesis study of flavivirus cross-reactive epitopes using West Nile virus-like particles - PubMed (original) (raw)

. 2007 Apr;88(Pt 4):1169-1174.

doi: 10.1099/vir.0.82640-0.

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A detailed mutagenesis study of flavivirus cross-reactive epitopes using West Nile virus-like particles

Wayne D Crill et al. J Gen Virol. 2007 Apr.

Abstract

Human flavivirus infections elicit virus species-specific and cross-reactive immune responses. The flavivirus envelope (E) glycoprotein is the primary antigen inducing protective immunity; however, the presence of cross-reactive antibodies in human sera creates problems for serodiagnosis. Using a West Nile virus-like particle system, we performed mutagenesis across all three E protein functional domains to identify epitope determinants for a panel of monoclonal antibodies (mAbs) raised against different flaviviruses and exhibiting diverse patterns of cross-reactivity. Residues within the highly conserved fusion peptide were the only epitope determinants identified and were important not only for broadly cross-reactive mAbs recognizing all of the medically important flavivirus serocomplexes, but also for less-broad, complex-reactive mAbs. Moreover, different substitutions at specific fusion peptide residues produced highly variable effects on antibody reactivity and virus-like particle secretion. These results support and extend the conclusion that the fusion peptide region constitutes an immunodominant epitope stimulating antibodies with diverse patterns of cross-reactivity.

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