@article{mbs:/content/journal/jgv/10.1099/vir.0.82640-0, author = "Crill, Wayne D. and Trainor, Nicole B. and Chang, Gwong-Jen J.", title = "A detailed mutagenesis study of flavivirus cross-reactive epitopes using West Nile virus-like particles", journal= "Journal of General Virology", year = "2007", volume = "88", number = "4", pages = "1169-1174", doi = "https://doi.org/10.1099/vir.0.82640-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.82640-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", 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.", }