Rockstroh Alexandra, Barzon Luisa, Pacenti Monia, Palù Giorgio, Niedrig Matthias, Ulbert Sebastian
Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
Department of Molecular Medicine, University of Padova, Padova, Italy.
PLoS Negl Trop Dis. 2015 Nov 13;9(11):e0004218. doi: 10.1371/journal.pntd.0004218. eCollection 2015 Nov.
Dengue virus (DENV) is a mosquito-borne flavivirus and a major international public health concern in many tropical and sub-tropical areas worldwide. DENV is divided into four major serotypes, and infection with one serotype leads to immunity against the same, but not the other serotypes. The specific diagnosis of DENV-infections via antibody-detection is problematic due to the high degree of cross-reactivity displayed by antibodies against related flaviviruses, such as West Nile virus (WNV), Yellow Fever virus (YFV) or Tick-borne encephalitis virus (TBEV). Especially in areas where several flaviviruses co-circulate or in the context of vaccination e.g. against YFV or TBEV, this severely complicates diagnosis and surveillance. Most flavivirus cross-reactive antibodies are produced against the highly conserved fusion loop (FL) domain in the viral envelope (E) protein. We generated insect-cell derived recombinant E-proteins of the four DENV-serotypes which contain point mutations in the FL domain. By using specific mixtures of these mutant antigens, cross-reactivity against heterologous flaviviruses was strongly reduced, enabling sensitive and specific diagnosis of the DENV-infected serum samples in IgG and IgM-measurements. These results have indications for the development of serological DENV-tests with improved specificity.
登革病毒（DENV）是一种由蚊子传播的黄病毒，是全球许多热带和亚热带地区主要的国际公共卫生问题。登革病毒分为四种主要血清型，感染一种血清型会产生针对该血清型的免疫力，但对其他血清型则无免疫力。由于针对相关黄病毒（如西尼罗河病毒（WNV）、黄热病病毒（YFV）或蜱传脑炎病毒（TBEV））的抗体表现出高度的交叉反应性，通过抗体检测对登革病毒感染进行特异性诊断存在问题。特别是在几种黄病毒共同传播的地区或在疫苗接种（如针对黄热病病毒或蜱传脑炎病毒）的情况下，这严重使诊断和监测复杂化。大多数黄病毒交叉反应性抗体是针对病毒包膜（E）蛋白中高度保守的融合环（FL）结构域产生的。我们生成了四种登革病毒血清型的昆虫细胞衍生重组E蛋白，这些蛋白在FL结构域中含有点突变。通过使用这些突变抗原的特定混合物，针对异源黄病毒的交叉反应性大大降低，从而能够在IgG和IgM检测中对登革病毒感染的血清样本进行灵敏且特异的诊断。这些结果为开发具有更高特异性的登革病毒血清学检测方法提供了依据。
