Zhang Shuai, Cao Yanan, Huang Yanjie, Zhang Xueli, Mou Chunxiao, Qin Tao, Chen Zhenhai, Bao Wenbin
College of Animal Science and Technology, Yangzhou University, Yangzhou, China.
College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
J Virol. 2025 Apr 15;99(4):e0013725. doi: 10.1128/jvi.00137-25. Epub 2025 Mar 26.
Porcine deltacoronavirus (PDCoV) is an emerging coronavirus causing economic losses to swine industries worldwide. PDCoV can infect chickens under laboratory conditions, usually with no symptoms or mild symptoms, and may cause outbreaks in backyard poultry and wildfowl, posing a potential risk of significant economic loss to the commercial poultry industry. However, the reasons for such a subdued reaction after infection are not known. Here, using chicken intestinal organoid monolayers, we found that although PDCoV infects them nearly as well as porcine intestinal organoid monolayers, infection did not result in detectable amounts of progeny virus. In and experiments using chickens, PDCoV infection failed to initiate interferon and inflammatory responses. Additionally, infection did not result in a disrupted intestinal barrier nor a reduced number of goblet cells and mucus secretion, as in pigs. In fact, the number of goblet cells increased as did the secreted mucus, thereby providing an enhanced protective barrier. PDCoV infection in chicken triggered activation of the Wnt/β-catenin pathway with the upregulation of Wnt/β-catenin pathway genes (, , , and ) and Wnt target genes (, , and ). This activation stimulates the self-renewal of intestinal stem cells (ISCs), accelerating ISC-mediated epithelial regeneration by significant up-regulation of (transiently amplifying cells), (ISCs), and (Paneth cells). Our data demonstrate that abortive infection of PDCoV in chicken cells activates the Wnt/β-catenin pathway, which facilitates the self-renewal and proliferation of ISCs, contributing to chickens' resistance to PDCoV infection.IMPORTANCEThe intestinal epithelium is the main target of PDCoV infection and serves as a physical barrier against pathogens. Additionally, ISCs are charged with tissue repair after injury, and promoting rapid self-renewal of intestinal epithelium will help to re-establish the physical barrier and maintain intestinal health. We found that PDCoV infection in chicken intestinal organoid monolayers resulted in abortive infection and failed to produce infectious virions, disrupt the intestinal barrier, reduce the number of goblet cells and mucus secretion, and induce innate immunity, but rather increased goblet cell numbers and mucus secretion. Abortive PDCoV infection activated the Wnt/β-catenin pathway, enhancing ISC renewal and accelerating the renewal and replenishment of shed PDCoV-infected intestinal epithelial cells, thereby enhancing chicken resistance to PDCoV infection. This study provides novel insights into the mechanisms underlying the mild or asymptomatic response to PDCoV infection in chickens, which is critical for understanding the virus's potential risks to the poultry industry.
猪德尔塔冠状病毒（PDCoV）是一种新出现的冠状病毒，给全球养猪业造成经济损失。在实验室条件下，PDCoV可感染鸡，通常无明显症状或仅有轻微症状，且可能在家养家禽和野禽中引发疫情，给商业家禽业带来重大经济损失的潜在风险。然而，感染后出现这种不明显反应的原因尚不清楚。在此，我们利用鸡肠道类器官单层培养物发现，尽管PDCoV对其感染能力与猪肠道类器官单层培养物相近，但感染并未产生可检测到的子代病毒。在对鸡进行的实验中，PDCoV感染未能引发干扰素和炎症反应。此外，与猪不同，感染并未导致肠道屏障破坏，也未使杯状细胞数量减少及黏液分泌降低。事实上，杯状细胞数量增加，黏液分泌也增多，从而提供了更强的保护屏障。鸡的PDCoV感染引发了Wnt/β-连环蛋白信号通路的激活，Wnt/β-连环蛋白信号通路相关基因（、、、和）以及Wnt靶基因（、、和）上调。这种激活刺激了肠道干细胞（ISC）的自我更新，通过显著上调（短暂扩增细胞）、（ISC）和（潘氏细胞）来加速ISC介导的上皮再生。我们的数据表明，鸡细胞中PDCoV的流产感染激活了Wnt/β-连环蛋白信号通路，这促进了ISC的自我更新和增殖，有助于鸡抵抗PDCoV感染。
重要性
肠道上皮是PDCoV感染的主要靶标，也是抵御病原体的物理屏障。此外，ISC负责损伤后的组织修复，促进肠道上皮的快速自我更新将有助于重新建立物理屏障并维持肠道健康。我们发现，鸡肠道类器官单层培养物中的PDCoV感染导致流产感染，未能产生有感染性的病毒粒子，未破坏肠道屏障，未减少杯状细胞数量和黏液分泌，也未诱导先天免疫，反而增加了杯状细胞数量和黏液分泌。PDCoV的流产感染激活了Wnt/β-连环蛋白信号通路，增强了ISC更新，并加速了被PDCoV感染的脱落肠道上皮细胞的更新和补充，从而增强了鸡对PDCoV感染的抵抗力。本研究为鸡对PDCoV感染出现轻微或无症状反应的潜在机制提供了新见解，这对于理解该病毒对家禽业的潜在风险至关重要。
