Trainor Nicole B, Crill Wayne D, Roberson Jill A, Chang Gwong-Jen J
Arboviral Diseases Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Service, Post Office Box 2087, Fort Collins, CO 80522, USA.
Virology. 2007 Apr 10;360(2):398-406. doi: 10.1016/j.virol.2006.10.033. Epub 2006 Dec 6.
The immune response to flavivirus infections produces both species-specific and flavivirus cross-reactive antibodies. The presence of cross-reactive antibodies complicates serodiagnosis of flavivirus infections, especially secondary infections caused by a heterologous virus. A successful public health response to the growing global threat posed by flaviviruses necessitates the development of virus-specific diagnostic antigens. The flavivirus envelope (E) glycoprotein is the principle antigen stimulating protective immunity during infection. Using recombinant St. Louis encephalitis virus-like particles (VLPs), we have identified amino acid residues involved in flavivirus cross-reactive epitope determinants. Most significant among the residues studied are three highly conserved amino acids in the fusion peptide: Gly104, Gly106, and Leu107. Substitutions of these residues dramatically influenced VLP secretion and cross-reactive monoclonal antibody reactivity. These results provide critical insight into the antigenic structure of the flaviviral E protein and toward development of species-specific diagnostic antigens that should improve both flavivirus diagnosis and estimates of disease burden.
针对黄病毒感染的免疫反应会产生物种特异性和黄病毒交叉反应性抗体。交叉反应性抗体的存在使黄病毒感染的血清学诊断变得复杂，尤其是由异源病毒引起的二次感染。要成功应对黄病毒对全球日益增长的威胁，就必须开发病毒特异性诊断抗原。黄病毒包膜（E）糖蛋白是感染期间刺激保护性免疫的主要抗原。利用重组圣路易斯脑炎病毒样颗粒（VLP），我们确定了参与黄病毒交叉反应性表位决定簇的氨基酸残基。在所研究的残基中，最重要的是融合肽中的三个高度保守的氨基酸：Gly104、Gly106和Leu107。这些残基的取代显著影响了VLP的分泌和交叉反应性单克隆抗体的反应性。这些结果为黄病毒E蛋白的抗原结构提供了关键见解，并有助于开发物种特异性诊断抗原，这有望改善黄病毒诊断和疾病负担评估。
