Antibody Responses to Zika Virus Infections in Environments of Flavivirus Endemicity
Antibody Responses to Zika Virus Infections in Environments of Flavivirus Endemicity
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DOI：
10.1128/cvi.00036-17
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发表时间：
2017-04-01
影响因子：
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通讯作者：
Ulrich, Robert G.
中科院分区：
文献类型：
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作者：
Keasey, Sarah L.;Pugh, Christine L.;Ulrich, Robert G.
寨卡病毒（ZIKV）感染发生在登革热病毒（DENV）、西尼罗河病毒（WNV）、黄热病病毒（YFV）和黄病毒属其他病毒共同传播的地区。这些密切相关的黄病毒的包膜 (E) 蛋白可诱导特异性长期免疫，但随后的感染与交叉反应性抗体反应相关，可能会增强疾病的易感性和严重程度。为了在类似病毒性疾病的背景下更好地了解 ZIKV 感染，我们检查了人类和非人灵长类动物 (NHP) 对 ZIKV、WNV、DENV 和 YFV 感染的血清学免疫反应。使用印刷微阵列，我们用来自 15 个物种和对人类致病的黄病毒谱系的重组 E 蛋白探针检测到了针对原发性感染的非常特异性的抗体反应，同时在 11 种印刷的天然病毒中观察到了 ZIKV 和 DENV 之间的高交叉反应性。值得注意的是，在黄病毒流行地区发生的人类原发性 ZIKV 或继发性 DENV 感染的抗体被广泛识别为许多黄病毒（尤其是 DENV）的 E 蛋白，这表明感染史对免疫反应有很大影响。根据血清抗体与多物种 E 蛋白组的相互作用，使用预测算法来初步识别之前与特定黄病毒的接触情况。这些结果说明了接触相关病毒对 ZIKV 感染结果的潜在影响，并为疫苗和诊断的开发提供了考虑。
Zika virus (ZIKV) infections occur in areas where dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), and other viruses of the genus Flavivirus cocirculate. The envelope (E) proteins of these closely related flaviviruses induce specific long-term immunity, yet subsequent infections are associated with cross-reactive antibody responses that may enhance disease susceptibility and severity. To gain a better understanding of ZIKV infections against a background of similar viral diseases, we examined serological immune responses to ZIKV, WNV, DENV, and YFV infections of humans and nonhuman primates (NHPs). Using printed microarrays, we detected very specific antibody responses to primary infections with probes of recombinant E proteins from 15 species and lineages of flaviviruses pathogenic to humans, while high cross-reactivity between ZIKV and DENV was observed with 11 printed native viruses. Notably, antibodies from human primary ZIKV or secondary DENV infections that occurred in areas where flavivirus is endemic broadly recognized E proteins from many flaviviruses, especially DENV, indicating a strong influence of infection history on immune responses. A predictive algorithm was used to tentatively identify previous encounters with specific flaviviruses based on serum antibody interactions with the multispecies panel of E proteins. These results illustrate the potential impact of exposure to related viruses on the outcome of ZIKV infection and offer considerations for development of vaccines and diagnostics.