Abstract：
Pain is often one of the initial indicators of a viral infection, yet our understanding of how viruses induce pain is limited. Immune cells typically recognize viral nucleic acids, which activate viral receptors and signaling, leading to immunity. Interestingly, these viral receptors and signals are also present in nociceptors and are associated with pain. Here, we investigate the response of nociceptors to nucleic acids during viral infections, specifically focusing on the role of the viral signal, Stimulator of Interferon Genes (STING). Our research shows that cytosolic double-stranded DNA (dsDNA) from viruses, like herpes simplex virus 1 (HSV-1), triggers pain responses through STING expression in nociceptors. In addition, STING agonists alone can elicit pain responses. Notably, these responses involve the direct activation of STING in nociceptors through TRPV1. We also provided a proof-of-concept showing that STING and TRPV1 significantly contribute to the mechanical hypersensitivity induced by HSV-1 infection. These findings suggest that STING could be a potential therapeutic target for relieving pain during viral infections.
摘要：
疼痛通常是病毒感染的初始指标之一，然而，我们对病毒如何引起疼痛的理解是有限的。免疫细胞通常识别病毒核酸，激活病毒受体和信号，导致豁免权。有趣的是,这些病毒受体和信号也存在于伤害感受器中，并与疼痛有关。这里,我们研究了在病毒感染期间伤害感受器对核酸的反应，特别关注病毒信号的作用，干扰素基因的刺激物(STING)。我们的研究表明，来自病毒的胞浆双链DNA（dsDNA），如单纯疱疹病毒1（HSV-1），通过STING在痛觉感受器中的表达触发疼痛反应。此外,单独的STING激动剂可以引起疼痛反应。值得注意的是,这些反应涉及通过TRPV1直接激活痛觉感受器中的STING。我们还提供了一个概念证明，表明STING和TRPV1对HSV-1感染引起的机械性超敏反应有显著贡献。这些发现表明STING可能是缓解病毒感染期间疼痛的潜在治疗靶标。
