Quality Control of Antibody Responses by the Innate Signaling Adaptor MAVS

摘要 通过模式识别受体（PRRs）对微生物化合物的先天免疫识别代表了一种免疫应答。 在控制适应性免疫反应中的中央调节检查点。Rig-I样受体（RLR）包括 PRR家族，包括RNA解旋酶RIG-I和MDA-5。RLR识别微生物RNA种类， 细胞质中，并依赖于必要的信号转导衔接子MAVS诱导细胞反应。RLR是 对多种病毒感染的先天免疫的重要介质。然而，RLRs在调节 适应性免疫仍然知之甚少。感染西尼罗河病毒（WNV）的MAVS缺陷小鼠不能 产生有效的病毒特异性中和抗体反应，表明MAVS的重要作用 控制体液免疫的信号传导。在这里，我们将采用单轮感染突变的西尼罗河病毒， 探索RLRs调节抗体应答质量控制的中心假设。我们的研究将 因此，解决了关于RLRs在适应性免疫应答中的作用的基本机制问题 西尼罗河病毒和其他RNA病毒。这些见解将推动新疫苗策略的发展， WNV和相关黄病毒。

ABSTRACT Innate immune recognition of microbial compounds by pattern recognition receptors (PRRs) represents a central regulatory checkpoint in the control of adaptive immune responses. Rig-I-like receptors (RLRs) comprise a PRR family that includes the RNA helicases RIG-I and MDA-5. RLRs recognize microbial RNA species in the cytosol and rely on the essential signaling adaptor MAVS for the induction of the cellular response. RLRs are important mediators of innate immunity to multiple viral infections. However, the role of RLRs in the regulation of adaptive immunity is still poorly understood. MAVS-deficient mice infected with West Nile Virus (WNV) fail to develop an effective virus-specific neutralizing antibody response, suggesting an important role for MAVS signaling in the control of humoral immunity. Here, we will employ a single-round-of-infection mutant of WNV to probe the central hypothesis that RLRs regulate the quality control of the antibody response. Our study will therefore address fundamental mechanistic questions about the role of RLRs in the adaptive immune response to WNV and other RNA viruses. Such insights will advance the development of novel vaccine strategies against WNV and related flaviviruses.