The protective effects of lactoferrin against murine norovirus infection through inhibition of both viral attachment and replication

The protective effects of lactoferrin against murine norovirus infection through inhibition of both viral attachment and replication
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DOI:
10.1016/j.bbrc.2013.04.013
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发表时间:
2013-05-17
影响因子:
3.1
通讯作者:
Kyuwa, Shigeru
Kyuwa, Shigeru
中科院分区:
生物学4区
文献类型:
--
作者:
Ishikawa, Hiroki;Awano, Naoki;Kyuwa, Shigeru

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采用小鼠诺如病毒(MNV)和Raw 264. 7细胞,研究牛乳铁蛋白对诺如病毒感染的抑制作用。当在存在或不存在乳铁蛋白的情况下用MNV感染Raw 264.7细胞时,与不存在乳铁蛋白相比,在存在15或20 μ g/孔的乳铁蛋白的情况下,对感染的Raw 264.7细胞的细胞毒性损伤显著且剂量依赖性地降低并被完全抑制。相应地,与对照感染的Raw 264.7细胞相比,在用乳铁蛋白处理的感染的Raw 264.7细胞中培养基和细胞内的MNV滴度显著降低。乳铁蛋白对MNV感染的保护作用的机制归因于其抑制初始MNV附着到细胞和随后干扰MNV复制。此外,揭示了在感染的早期阶段,乳铁蛋白可以快速诱导抗病毒细胞因子mRNA的表达,如IFN-α和IFN-β,其参与抑制感染的Raw 264.7细胞中的MNV复制。由此得出结论,乳铁蛋白通过抑制病毒附着和复制而对MNV感染发挥保护作用。本结果提供了乳铁蛋白可用作预防性和/或治疗性抗诺如病毒剂的证据。(C)2013 Elsevier Inc. All rights reserved.
The purpose of this study was to evaluate the effects of bovine lactoferrin against norovirus infection using mouse norovirus (MNV) and Raw264.7 cell in vitro. When Raw264.7 cells were infected with MNV in the presence or absence of lactoferrin, the cytotoxic damage to the infected Raw264.7 cells significantly and dose-dependently decreased and completely inhibited in the presence of 15 or 20 mu g/well of lactoferrin as compared with the absence of lactoferrin. Correspondingly, the MNV titers in the culture medium and intracellularly were significantly decreased in infected Raw264.7 cells treated with lactoferrin compared to control infected Raw264.7 cells. The mechanisms responsible for the protective effects of lactoferrin against MNV infection were attributed to both its inhibition of the initial MNV attachment to cells and the subsequent interference with MNV replication. Moreover, it was revealed that lactoferrin could rapidly induce the expression of anti-viral cytokine mRNA, such as IFN-alpha and IFN-beta which involved in inhibition of MNV replication in infected Raw264.7 cells, in the early phase of infection. It was concluded that lactoferrin exerts protective effects against MNV infection through inhibition of both viral attachment and replication. The present results provide evidence that lactoferrin may be useful as a preventive and/or therapeutic anti-norovirus agent. (C) 2013 Elsevier Inc. All rights reserved.