Calpain-1: a Novel Antiviral Host Factor Identified in Porcine Small Intestinal Mucus.
Calpain-1: a Novel Antiviral Host Factor Identified in Porcine Small Intestinal Mucus.
复制标题
作者：
由于其在肠道感染中的保护作用，覆盖在肠上皮上的厚粘液层越来越受到关注。然而，粘液增加肠道抵抗病毒感染的确切机制仍不清楚。在这里，我们确定了突出的抗病毒活性的小肠粘液和提取的总粘液蛋白，证明了它们对猪流行性腹泻病毒（PEDV）感染的抑制作用。在所有提取的粘液蛋白中，粘蛋白2和组分III（~70 kDa）表现出有效的抗病毒活性。我们进一步评估了组分III中三个候选因子的抗病毒作用，发现钙蛋白酶-1对其抗病毒活性有很大贡献。体内研究表明，口服钙蛋白酶-1提供了有效的保护，防止肠道PEDV感染。作为一种钙激活的半胱氨酸蛋白酶，calpain-1通过结合并水解病毒刺突蛋白的S1结构域来抑制病毒的入侵。PEDV S1蛋白的B结构域中氨基酸297和337之间的区域对于钙蛋白酶-1介导的水解是关键的。进一步研究表明，钙蛋白酶-1可由肠上皮之间的杯状细胞产生。综上所述，我们的研究结果显示calpain-1是猪小肠粘液中的一种新的抗病毒蛋白，表明calpain-1具有抵抗肠道感染的潜力。
The thick mucus layer covering of the intestinal epithelium has received increasing attention, owing to its protective role in intestinal infection. However, the exact mechanisms by which the mucus increases intestinal resistance against viral infection remain largely unclear. Here, we identify prominent antiviral activity of the small intestinal mucus and extracted total mucus proteins, as evidenced by their inhibitory effects against porcine epidemic diarrhea virus (PEDV) infection. Of all the extracted mucus proteins, mucin 2 and fraction III (~70 kDa) exhibited potent antiviral activity. We further evaluated the antiviral effects of three candidate factors in fraction III and found that calpain-1 contributed substantially to its antiviral activity. In vivo studies demonstrated that oral administration of calpain-1 provided effective protection against intestinal PEDV infection. As a calcium-activated cysteine protease, calpain-1 inhibited viral invasion by binding to and hydrolyzing the S1 domain of the viral spike protein. The region between amino acids 297 and 337 in the b domain of PEDV S1 protein was critical for calpain-1-mediated hydrolysis. Further investigation indicated that calpain-1 could be produced by goblet cells between intestinal epithelia. Taken together, the results of our study revealed calpain-1 to be a novel antiviral protein in porcine small intestinal mucus, suggesting that calpain-1 has potential for defending against intestinal infections.
登录
查看更多内容
DOI：
10.1038/nri.2016.88
发表时间：
2016-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Johansson ME;Hansson GC
通讯作者：
Hansson GC
影响因子：
3.7
作者：
Boshuizen, JA;Reimerink, JHJ;Einerhand, AWC
通讯作者：
Einerhand, AWC
DOI：
10.3390/pathogens2010055
发表时间：
2013-02-04
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
Kim JJ;Khan WI
通讯作者：
Khan WI
影响因子：
5.4
作者：
Ambort, Daniel;Johansson, Malin E. V.;Hansson, Gunnar C.
通讯作者：
Hansson, Gunnar C.
影响因子：
5.4
作者：
Feng, Ningguo;Yasukawa, Linda L.;Greenberg, Harry B.
通讯作者：
Greenberg, Harry B.