Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
J Clin Microbiol. 2018 Feb 22;56(3). doi: 10.1128/JCM.01504-17. Print 2018 Mar.
Zika virus (ZIKV) is an emerging flavivirus that can cause birth defects and neurologic complications. Molecular tests are effective for diagnosing acute ZIKV infection, although the majority of infections produce no symptoms at all or present after the narrow window in which molecular diagnostics are dependable. Serology is a reliable method for detecting infections after the viremic period; however, most serological assays have limited specificity due to cross-reactive antibodies elicited by flavivirus infections. Since ZIKV and dengue virus (DENV) widely cocirculate, distinguishing ZIKV infection from DENV infection is particularly important for diagnosing individual cases or for surveillance to coordinate public health responses. Flaviviruses also elicit type-specific antibodies directed to non-cross-reactive epitopes of the infecting virus; such epitopes are attractive targets for the design of antigens for development of serological tests with greater specificity. Guided by comparative epitope modeling of the ZIKV envelope protein, we designed two recombinant antigens displaying unique antigenic regions on domain I (Z-EDI) and domain III (Z-EDIII) of the ZIKV envelope protein. Both the Z-EDI and Z-EDIII antigens consistently detected ZIKV-specific IgG in ZIKV-immune sera but not cross-reactive IgG in DENV-immune sera in late convalescence (>12 weeks postinfection). In contrast, during early convalescence (2 to 12 weeks postinfection), secondary DENV-immune sera and some primary DENV-immune sera cross-reacted with the Z-EDI and Z-EDIII antigens. Analysis of sequential samples from DENV-immune individuals demonstrated that Z-EDIII cross-reactivity peaked in early convalescence and declined steeply over time. The Z-EDIII antigen has much potential as a diagnostic antigen for population-level surveillance and for detecting past infections in patients.
Zika 病毒（ZIKV）是一种新兴的黄病毒，可导致出生缺陷和神经并发症。分子检测可有效诊断急性 ZIKV 感染，但大多数感染根本没有症状，或者在分子诊断可靠的狭窄窗口期之后出现症状。血清学是一种在病毒血症期后检测感染的可靠方法；然而，由于黄病毒感染引起的交叉反应性抗体，大多数血清学检测方法特异性有限。由于 ZIKV 和登革热病毒（DENV）广泛共同传播，因此区分 ZIKV 感染和 DENV 感染对于诊断个体病例或监测以协调公共卫生应对措施尤为重要。黄病毒还会产生针对感染病毒非交叉反应性表位的特异性抗体；这些表位是设计用于开发具有更高特异性的血清学检测抗原的有吸引力的目标。受 ZIKV 包膜蛋白比较表位建模的指导，我们设计了两种展示 ZIKV 包膜蛋白结构域 I（Z-EDI）和结构域 III（Z-EDIII）上独特抗原区域的重组抗原。在恢复期后期（感染后>12 周），Z-EDI 和 Z-EDIII 抗原均能在 ZIKV 免疫血清中检测到 ZIKV 特异性 IgG，但不能在 DENV 免疫血清中检测到交叉反应性 IgG。相比之下，在恢复期早期（感染后 2 至 12 周），二次 DENV 免疫血清和一些初次 DENV 免疫血清与 Z-EDI 和 Z-EDIII 抗原发生交叉反应。对 DENV 免疫个体的连续样本进行分析表明，Z-EDIII 交叉反应性在恢复期早期达到峰值，并随时间急剧下降。Z-EDIII 抗原作为人群水平监测的诊断抗原和检测患者既往感染的抗原具有很大潜力。
