[en] Swine enteric coronaviruses (SeCoVs) infection pose a significant threat to the global swine industry, manifesting as symptoms such as vomiting, watery diarrhea, severe dehydration, and high mortality rates, especially among neonatal piglets. The intestinal barrier serves as a critical defense against intestinal microorganisms and plays a pivotal role in maintaining host homeostasis. This barrier comprises the mucus layer, intestinal epithelium, intestinal microbiota and underlying immune cells. However, the role of the intestinal barrier in countering SeCoVs infection and its influence on viral susceptibility remain poorly understood. In addition, the inherent limitations of existing cell models further complicate the study of the interaction between SeCoVs and the intestinal barrier.
In the first part of our study, we investigated the factors contributing to the heightened susceptibility of neonatal piglets to SeCoVs infection, with a focus on the intestinal barrier. Our findings reveal that one-week-old piglets exhibit longer intestinal villi with reduced crypt depth, underdeveloped epithelial cells, a lower presence of probiotic bacteria, and an immature immune system compared to older pigs. Furthermore, one-week-old piglets show elevated levels of proteins that assist enteric virus invasion but lower levels of resistance proteins. These factors collectively provide a reasonable explanation for SeCoVs susceptibility in neonatal piglets.
The second part of our research explores the impact of the intestinal epithelium on SeCoVs invasion. We developed a porcine intestinal organoid monolayer to investigate the interaction of transmissible gastroenteritis virus (TGEV) with the intestinal epithelium. Our results demonstrate that TGEV infection induces interferon (IFN) and inflammatory responses in this organoid model, but it does not disturb the integrity of the intestinal epithelium. Further investigation revealed that TGEV infection stimulates the proliferation of intestinal stem cells (ISCs) through the activation of the Wnt/β-catenin pathway, promoting the self-renewal of epithelial cells and thereby preserving epithelial integrity.
The third part of our study focuses on the role of the mucus layer in SeCoVs invasion. We developed a porcine intestinal organoid monolayer with a mucus layer to investigate SeCoVs infection within this context. Our results indicate that the mucus layer acts as a protective barrier against porcine epidemic diarrhea virus (PEDV) and TGEV infections. Further investigation revealed that mucin 2 (Muc2) exerts antiviral activity in this infection scenario. Additionally, neuraminidase (NA) treatment effectively alleviates the inhibitory effect of Muc2 on SeCoVs infection, highlighting the role of sialic acid modification of Muc2 in its antiviral activity.
In conclusion, this thesis provides an in-depth analysis of the factors contributing to the high susceptibility of newborn piglets to SeCoVs from the perspective of the intestinal barrier. It also explores the interactions between SeCoVs and the intestinal epithelium and mucus layer through the development of an intestinal organoid system. These findings offer a comprehensive understanding of the role of the intestinal barrier in SeCoVs infection and provide valuable insights for the development of prevention and control strategies against SeCoVs.
Research Center/Unit :
Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Yang, Ning ; Université de Liège - ULiège > TERRA Research Centre
Language :
English
Title :
Exploring the role of intestinal barrier in swine enteric coronaviruses infection
Willems, Luc ; Université de Liège - ULiège > GIGA > GIGA Cancer - Cellular and Molecular Epigenetics ; Université de Liège - ULiège > Département GxABT > Microbial technologies
Liu Guangliang; Chinese Academy of Agricultural Sciences > Lanzhou Veterinary Research Institute > Animal immunology group
President :
Mahy, Grégory ; Université de Liège - ULiège > TERRA Research Centre > Biodiversité et Paysage ; Université de Liège - ULiège > Département GxABT > Biodiversité et Paysage
Jury member :
NAUWYNCK Hans; UGent - Ghent University [BE] > Faculty of Veterinary Medicine > Laboratory of Virology
Massart, Sébastien ; Université de Liège - ULiège > TERRA Research Centre > Gestion durable des bio-agresseurs ; Université de Liège - ULiège > Département GxABT > Gestion durable des bio-agresseurs
Schroyen, Martine ; Université de Liège - ULiège > Département GxABT > Animal Sciences (AS) ; Université de Liège - ULiège > Département GxABT
Hamaïdia, Malik ; Université de Liège - ULiège > Département GxABT > Microbial technologies
Development Goals :
3. Good health and well-being
Name of the research project :
Exploring the role of intestinal barrier in swine enteric coronaviruses infection
Funders :
NSCF - National Natural Science Foundation of China [CN]
Funding number :
31972689
Funding text :
This work was supported by the National Natural Science Foundation of China (31972689) and ULg-CAAS joint Ph.D.
Program.