Quality Control of Antibody Responses by the Innate Signaling Adaptor MAVS

摘要 模式识别受体(PRRs)对微生物化合物的天然免疫识别 在控制适应性免疫反应中的中央调节检查点。Rig-I样受体(RLRs)包括 包括RNA解旋酶RIG-I和MDA-5的PRR家族。RLR识别细菌中的微生物RNA物种 细胞溶质，并依赖于重要的信号转接器MAV来诱导细胞反应。RLR是 对多种病毒感染的先天免疫的重要媒介。然而，RLRs在调节 获得性免疫仍然知之甚少。感染西尼罗河病毒(WNV)的MAVS缺陷小鼠未能 发展有效的病毒特异性中和抗体反应，提示MAV发挥重要作用 体液免疫控制中的信号传递。在这里，我们将使用西尼罗河病毒的单轮感染突变体来 探索RLRs调节抗体反应质量控制的中心假设。我们的研究将 因此，解决有关RLRs在获得性免疫反应中的作用的基本机制问题 对西尼罗河病毒和其他RNA病毒。这些洞察力将推动新疫苗策略的发展 西尼罗河病毒及相关的黄病毒。

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.