Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109, USA.
Antiviral Res. 2012 Jun;94(3):258-71. doi: 10.1016/j.antiviral.2012.03.005. Epub 2012 Mar 23.
Rhinovirus (RV), which is responsible for the majority of common colds, also causes exacerbations in patients with asthma and chronic obstructive pulmonary disease. So far, there are no drugs available for treatment of rhinovirus infection. We examined the effect of quercetin, a plant flavanol on RV infection in vitro and in vivo. Pretreatment of airway epithelial cells with quercetin decreased Akt phosphosphorylation, viral endocytosis and IL-8 responses. Addition of quercetin 6h after RV infection (after viral endocytosis) reduced viral load, IL-8 and IFN responses in airway epithelial cells. This was associated with decreased levels of negative and positive strand viral RNA, and RV capsid protein, abrogation of RV-induced eIF4GI cleavage and increased phosphorylation of eIF2α. In mice infected with RV, quercetin treatment decreased viral replication as well as expression of chemokines and cytokines. Quercetin treatment also attenuated RV-induced airway cholinergic hyperresponsiveness. Together, our results suggest that quercetin inhibits RV endocytosis and replication in airway epithelial cells at multiple stages of the RV life cycle. Quercetin also decreases expression of pro-inflammatory cytokines and improves lung function in RV-infected mice. Based on these observations, further studies examining the potential benefits of quercetin in the prevention and treatment of RV infection are warranted.
鼻病毒(RV)是引起普通感冒的主要原因,也是哮喘和慢性阻塞性肺疾病患者病情加重的原因。目前尚无治疗鼻病毒感染的药物。我们研究了植物黄烷醇槲皮素对鼻病毒感染的体外和体内作用。鼻病毒感染前用槲皮素处理气道上皮细胞可降低 Akt 的磷酸化、病毒内吞作用和 IL-8 反应。鼻病毒感染 6 小时后(病毒内吞作用后)添加槲皮素可降低气道上皮细胞中的病毒载量、IL-8 和 IFN 反应。这与负链和正链病毒 RNA 以及 RV 衣壳蛋白水平降低、RV 诱导的 eIF4GI 裂解减少以及 eIF2α 磷酸化增加有关。在感染 RV 的小鼠中,槲皮素治疗可降低病毒复制以及趋化因子和细胞因子的表达。槲皮素治疗还可减轻 RV 诱导的气道胆碱能高反应性。综上所述,我们的研究结果表明,槲皮素可在鼻病毒生命周期的多个阶段抑制气道上皮细胞中的病毒内吞和复制。槲皮素还可降低 RV 感染小鼠中促炎细胞因子的表达并改善肺功能。基于这些观察结果,进一步研究槲皮素在预防和治疗 RV 感染中的潜在益处是有必要的。