Besides antigen-specific responses to viral antigens, humoral immune response in virus infection can generate polyreactive and autoreactive antibodies. Dengue and Zika virus infections have been linked to antibody-mediated autoimmune disorders, including Guillain-Barré syndrome. A unique feature of flaviviruses is the secretion of nonstructural protein 1 (NS1) by infected cells. NS1 is highly immunogenic, and antibodies targeting NS1 can have both protective and pathogenic roles. In the present study, we investigated the humoral immune response to Zika virus NS1 and found NS1 to be an immunodominant viral antigen associated with the presence of autoreactive antibodies. Through single B cell cultures, we coupled binding assays and BCR sequencing, confirming the immunodominance of NS1. We demonstrate the presence of self-reactive clones in germinal centers after both infection and immunization, some of which present cross-reactivity with NS1. Sequence analysis of anti-NS1 B cell clones showed sequence features associated with pathogenic autoreactive antibodies. Our findings demonstrate NS1 immunodominance at the cellular level as well as a potential role for NS1 in ZIKV-associated autoimmune manifestations.

中文翻译：

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对寨卡病毒 NS1 蛋白的免疫显性抗体反应的特点是对自身的交叉反应

除了对病毒抗原的抗原特异性反应外，病毒感染中的体液免疫反应还可以产生多反应性和自身反应性抗体。登革热和寨卡病毒感染与抗体介导的自身免疫性疾病有关，包括格林-巴利综合征。黄病毒的一个独特特征是受感染细胞分泌非结构蛋白 1 (NS1)。NS1 具有高度免疫原性，针对 NS1 的抗体可以同时具有保护和致病作用。在本研究中，我们研究了对寨卡病毒 NS1 的体液免疫反应，发现 NS1 是一种与自身反应性抗体存在相关的免疫优势病毒抗原。通过单 B 细胞培养，我们将结合测定和 BCR 测序相结合，证实了 NS1 的免疫优势。我们证明了感染和免疫后在生发中心存在自我反应性克隆，其中一些与 NS1 存在交叉反应性。抗 NS1 B 细胞克隆的序列分析显示与致病性自身反应性抗体相关的序列特征。我们的研究结果证明了 NS1 在细胞水平上的免疫优势以及 NS1 在 ZIKV 相关的自身免疫表现中的潜在作用。