Targeting Host Cell Surface Nucleolin for RSV Therapy: Challenges and Opportunities.
Targeting Host Cell Surface Nucleolin for RSV Therapy: Challenges and Opportunities.
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DOI：
10.3390/vaccines5030027
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发表时间：
2017-09-19
期刊：
影响因子：
7.8
通讯作者：
Hegele RG
中科院分区：
文献类型：
--
作者：
Mastrangelo P;Norris MJ;Duan W;Barrett EG;Moraes TJ;Hegele RG
核仁素(NCL)是人类呼吸道合胞病毒(RSV)的细胞受体。我们研究了AS1411的作用，AS1411是一种结合细胞表面NCL的抗癌化合物，作为一种可能的体外和体内RSV治疗的新策略。AS1411作用于RSV感染的非极化(HEP-2)和极化(MDCK)上皮细胞，以及病毒感染的小鼠和棉花大鼠。体外实验结果表明，微摩尔浓度的AS1411与病毒阳性细胞数量的减少有关。与未经治疗的感染动物相比，鼻腔注射AS1411(50 mg/kg)可部分降低呼吸道合胞病毒感染小鼠和棉花大鼠的肺部病毒滴度，减少病毒相关的呼吸道炎症，并降低IL-4/干扰素-γ比率。总之，我们的研究结果表明，AS1411的治疗应用对RSV复制和宿主反应的影响不大。虽然这些结果强调了靶向细胞表面NCL作为RSV治疗的潜在新策略的挑战，但它们也强调了细胞表面NCL作为治疗靶点的潜力。
Nucleolin (NCL) has been reported as a cellular receptor for the human respiratory syncytial virus (RSV). We studied the effects of re-purposing AS1411, an anti-cancer compound that binds cell surface NCL, as a possible novel strategy for RSV therapy in vitro and in vivo. AS1411 was administered to RSV-infected cultures of non-polarized (HEp-2) and polarized (MDCK) epithelial cells and to virus-infected mice and cotton rats. Results of in vitro experiments showed that AS1411, used in micromolar concentrations, was associated with decreases in the number of virus-positive cells. Intranasal administration of AS1411 (50 mg/kg) to RSV-infected mice and cotton rats was associated with partial reductions in lung viral titers, decreased virus-associated airway inflammation, and decreased IL-4/IFN-γ ratios when compared to untreated, infected animals. In conclusion, our findings indicate that therapeutic use of AS1411 has modest effects on RSV replication and host response. While the results underscore the challenges of targeting cell surface NCL as a potential novel strategy for RSV therapy, they also highlight the potential of cell surface NCL as a therapeutic target.
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DOI：
10.1165/rcmb.2002-0115oc
发表时间：
2003-06-01
影响因子：
6.4
作者：
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