Therapy of allergic rhinitis using ribavirin spray to clear nasal commensal viruses

Much attention has focused on commensal bacteria in health and disease, but the role of commensal viruses is largely unexplored. Although commensal viruses are suggested in some organs such as intestine to maintain tissue homeostasis, it is unknown whether they participate in the physiology or pathology of nose, which directly contacts outer environment. Here, we focused on nasal commensal viruses in the development of allergic rhinitis (AR), a global health problem affecting 20% to 30% of the population, and found that clearance of nasal commensal viruses using ribavirin alleviated AR symptoms, suggesting that nasal commensal viruses promote AR development. Mechanistically, nasal commensal viruses, recognized by innate sensors, initiated the production of type I interferon, recruiting and generating a population of interferon-induced neutrophils in the nasal cavity, which released neutrophil extracellular traps (NETs) to promote AR. Most importantly, to verify whether clearing nasal commensal viruses could treat AR patients clinically, we performed a randomized, double-blind, placebo-controlled, phase 2 clinical trial (Chinese Clinical Trial Registry identifier: ChiCTR2400082642) to explore the efficacy and safety of ribavirin spray in treating AR patients, and found that the patients of ribavirin group experienced significantly alleviated symptoms as compared to the placebo group, determining the therapeutic efficacy of ribavirin spray. Thus, we suggest a new mechanism for AR and a new approach for treating AR patients.

学界对共生细菌在健康与疾病中的作用已有广泛研究，但共生病毒的功能却尚未得到充分探索。尽管有研究表明，肠道等器官中的共生病毒可维持组织稳态，但尚不清楚共生病毒是否参与直接接触外界环境的鼻腔的生理与病理过程。本研究聚焦于与变应性鼻炎（allergic rhinitis, AR）发病相关的鼻腔共生病毒——变应性鼻炎是影响20%~30%人群的全球性健康问题——研究发现，使用利巴韦林清除鼻腔共生病毒可缓解变应性鼻炎症状，提示鼻腔共生病毒可促进变应性鼻炎的发生发展。从机制上看，鼻腔共生病毒可被天然免疫感受器识别，进而启动I型干扰素的产生，招募并诱导鼻腔内产生干扰素诱导型中性粒细胞，后者释放中性粒细胞胞外陷阱（neutrophil extracellular traps, NETs）以促进变应性鼻炎的发生。尤为重要的是，为验证清除鼻腔共生病毒能否在临床中治疗变应性鼻炎患者，本研究开展了一项随机双盲安慰剂对照II期临床试验（中国临床试验注册中心编号：ChiCTR2400082642），探究利巴韦林鼻喷剂治疗变应性鼻炎患者的有效性与安全性；结果显示，利巴韦林组患者的症状较安慰剂组显著缓解，证实了利巴韦林鼻喷剂的治疗效果。综上，本研究揭示了变应性鼻炎的全新发病机制，并为变应性鼻炎患者提供了新的治疗策略。