A mucus layer derived from porcine intestinal organoid air-liquid interface monolayer attenuates swine enteric coronavirus infection by antiviral activity of Muc2
文献类型： 外文期刊
作者： Yang, Ning 1 ; Li, Yang 1 ; Cai, Yifei 1 ; Liu, Yuanyuan 1 ; Zhang, Yunhang 1 ; Fu, Yuguang 1 ; Tan, Chen 1 ; Willems, Luc 2 ; Liu, Guangliang 1 ;
作者机构： 1.Chinese Acad Agr Sci, Lanzhou Univ, Lanzhou Vet Res Inst, Coll Vet Med,State Key Lab Anim Dis Control & Prev, Lanzhou, Peoples R China
2.Univ Liege, Mol & Cellular Epigenet GIGA & Mol Biol TERRA, Liege, Belgium
3.Hainan Acad Agr Sci, Inst Anim Husb & Vet Med, Hainan Key Lab Trop Anim Breeding & Infect Dis Res, Haikou, Peoples R China
4.Wageningen Univ & Res, Nutr Biol, Wageningen, Netherlands
5.Xinjiang Agr Univ, Coll Vet Med, Urumqi, Peoples R China
关键词： Coronavirus; Intestinal organoid monolayer; Air-liquid interface (ALI); Mucus layer; Muc2; Sialic acid
期刊名称：BMC BIOLOGY （ 影响因子：4.5； 五年影响因子：5.4 ）
ISSN：
年卷期： 2024 年 22 卷 1 期
页码：
收录情况： SCI
摘要： BackgroundThe mucus layer provides the first defense that keeps the epithelium free from microorganisms. However, the effect of the small intestinal mucus layer on pathogen invasion is still poorly understood, especially for swine enteric coronavirus. To better understand virus-mucus layer-intestinal epithelium interactions, here, we developed a porcine intestinal organoid mucus-monolayer model under air-liquid interface (ALI) conditions.ResultsWe successfully established a differentiated intestinal organoid monolayer model comprising various differentiated epithelial cell types and a mucus layer under ALI conditions. Mass spectrometry analysis revealed that the mucus derived from the ALI monolayer shared a similar composition to that of the native small intestinal mucus. Importantly, our results demonstrated that the ALI monolayer exhibited lower infectivity of both TGEV and PEDV than did the submerged monolayer. To further confirm the impact of ALI mucus on coronavirus infection, mucus was collected from the ALI monolayer culture system and incubated with the viruses. These results indicated that ALI mucus treatment effectively reduced the infectivity of TGEV and PEDV. Additionally, Mucin 2 (Muc2), a major component of native small intestinal mucus, was found to be abundant in the mucus derived from the ALI monolayer, as determined by mass spectrometry analysis. Our study confirmed the potent antiviral activity of Muc2 against TGEV and PEDV infection. Considering the sialylation of Muc2 and the known sialic acid-binding activity of coronavirus, further investigations revealed that the sialic acid residues of Muc2 play a potential role in inhibiting coronavirus infection.ConclusionsWe established the porcine intestinal organoid mucus monolayer as a novel and valuable model for confirming the pivotal role of the small intestinal mucus layer in combating pathogen invasion. In addition, our findings highlight the significance of sialic acid modification of Muc2 in blocking coronavirus infections. This discovery opens promising avenues for the development of tailor-made drugs aimed at preventing porcine enteric coronavirus invasion.
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