Inflammatory and oxidative stress in rotavirus infection.
Inflammatory and oxidative stress in rotavirus infection.
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DOI：
10.5501/wjv.v5.i2.38
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发表时间：
2016-05-12
期刊：
影响因子：
--
通讯作者：
Acosta, Orlando
中科院分区：
文献类型：
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作者：
Guerrero, Carlos A;Acosta, Orlando
轮状病毒是影响 5 岁以下儿童的危及生命的腹泻的唯一主要原因。轮状病毒进入宿主细胞似乎是通过病毒体蛋白和各种细胞表面分子之间的顺序相互作用而发生的。进入机制似乎涉及具有结合、陪伴和氧化还原活性的细胞分子的贡献。轮状病毒的受体使用和趋向性似乎是由物种、细胞系和轮状病毒株决定的。轮状病毒已进化出可以拮抗宿主先天免疫反应的功能，同时能够诱导内质网（ER）应激、氧化应激和炎症信号传导。内质网应激、炎症和氧化应激之间存在网络关系，其中内质网钙的释放增加了线粒体活性氧（ROS）的产生，导致内质网和线粒体内ROS的毒性积累。持续的内质网应激可能通过未折叠的蛋白质反应途径刺激炎症反应。然而，仍然缺乏支持这些轮状病毒诱导的应激条件的分子机制的详细表征。由宿主识别病毒相关分子模式引发的信号事件为开发旨在干扰轮状病毒感染的新型治疗策略提供了机会。利用N-乙酰半胱氨酸、非甾体抗炎药和PPARγ激动剂抑制轮状病毒感染，为治疗轮状病毒引起的腹泻和补充疫苗开辟了新途径。
Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum (ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species (ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virus-associated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARgamma agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines.