A detailed mutagenesis study of flavivirus cross-reactive epitopes using West Nile virus-like particles.
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.
Crill
Wayne D
WD
Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Service, PO Box 2087, Fort Collins, CO 80522, USA.
Trainor
Nicole B
NB
Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Service, PO Box 2087, Fort Collins, CO 80522, USA.
Chang
Gwong-Jen J
GJ
Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Service, PO Box 2087, Fort Collins, CO 80522, USA.
D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003429:Cross Reactions; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D016297:Mutagenesis, Site-Directed; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D016056:Immunodominant Epitopes; D014759:Viral Envelope Proteins