Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, PR China; Institute of Nanomedicine Technology, Department of Laboratory Medicine, Institutional Key Laboratory of Clinical Laboratory Diagnostics, 12th 5-Year Project of Shandong Province, Weifang Medical University, Weifang, Shandong, 261053, PR China.
Key laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, PR China.
Virus Res. 2017 Feb 2;229:57-64. doi: 10.1016/j.virusres.2016.12.003. Epub 2016 Dec 6.
Antibody-dependent enhancement (ADE) is currently considered as the mechanism underlying the pathogenesis of severe dengue disease. Many studies have shown that precursor (pr) peptide-specific antibodies do not efficiently neutralize infection but potently promote ADE of dengue virus (DENV) infection. To explore the effect of pr peptide substitution on neutralization and ADE of DENV infection, the rabbit anti-prM polyclonal antibodies (pAbs) and anti-JEVpr/DENV-M pAbs were prepared, and the neutralization and ADE of these two pAbs were further compared. Here, we report that both anti-JEVpr/DENV-M and anti-prM pAbs exhibited broad cross-reactivity and only partial neutralization with four DENV serotypes and immature DENV. Rabbit anti-prM pAbs showed a significant enhancement in a broad range of serum dilutions. However, there was no statistically significant difference in the enhancing activity of rabbit anti-JEVpr/DENV-M pAbs at various levels of dilution. These results demonstrate that anti-prM antibody-mediated ADE can be prevented by JEV pr peptide replacement. The present study contribute further to research on the pathogenesis of DENV infection.
抗体依赖的增强作用（ADE）目前被认为是严重登革热疾病发病机制的基础。许多研究表明，前体（pr）肽特异性抗体不能有效地中和感染，但能有效地促进登革病毒（DENV）感染的 ADE。为了探讨 pr 肽取代对 DENV 感染中和和 ADE 的影响，制备了兔抗 prM 多克隆抗体（pAbs）和抗 JEVpr/DENV-M pAbs，并进一步比较了这两种 pAbs 的中和和 ADE。在这里，我们报告说，抗 JEVpr/DENV-M 和抗 prM pAbs 均表现出广泛的交叉反应性，仅对四种 DENV 血清型和未成熟的 DENV 具有部分中和作用。兔抗 prM pAbs 在广泛的血清稀释度范围内显示出显著的增强作用。然而，在不同稀释度水平，兔抗 JEVpr/DENV-M pAbs 的增强活性没有统计学上的显著差异。这些结果表明，JEV pr 肽的替换可以预防抗 prM 抗体介导的 ADE。本研究为进一步研究 DENV 感染的发病机制做出了贡献。
