Classical swine fever virus (CSFV), a classic swine fever pathogen, causes severe economic losses worldwide. Poly (rC)-binding protein 1 (PCBP1), which interacts with N-pro of CSFV, plays a vital role in CSFV growth. We are the first to report the generation of PCBP1-deficient pigs via gene-editing technology. The PCBP1-deficient pigs exhibited normal birth weight and reproductive-performance traits and developed normally. Viral challenge experiments indicated that primary cells isolated from F-0- and F-1-generation pigs exhibited significantly reduced CSFV infection. Additional mechanistic exploration further confirmed that the PCBP1 deficiency-mediated antiviral effect is related to the activation of type I interferon (IFN). Besides showing that a gene-editing strategy could be used to generate PCBP1-deficient pigs, our study introduces a valuable animal model for further investigating the infection mechanisms of CSFV that will help to develop better antiviral solutions.

Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, is a serious threat to piglets and has zoonotic potential. Here, we aimed to further explore the role of aminopeptidase N (APN) as a receptor for PDCoV and test the inhibitory effect of a chimeric APN protein strategy on PDCoV infection. PK-15 cells and LLC-PK1 cells expressing chimeric APN were selected and infected with PDCoV. Viral replication was significantly decreased in these chimeric APN cells compared with that in control group cells. To further characterize the effect of the chimeric APN strategy on PDCoV infection in vitro , primary intestinal epithelial cells isolated from chimeric APN pigs were inoculated with PDCoV. Viral challenge of these cells led to decreased PDCoV infection. More importantly, virally challenged chimeric APN neonatal piglets displayed reduced viral load, significantly fewer microscopic lesions in the intestinal tissue, and no diarrhea. Taken together, these findings deepen our understanding of the mechanism of PDCoV infection and provide a valuable model for the production of disease-resistant animals. IMPORTANCE: Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, causes diarrhea in piglets and possesses the potential to infect humans. However, there are currently no effective measures for the prevention or control of PDCoV infection. Here, we have developed PK-15 cells, LLC-PK1 cells, and primary intestinal epithelial cells expressing chimeric APN, and viral challenge of these cells led to decreased PDCoV infection. Furthermore, virally challenged chimeric APN neonatal piglets displayed reduced viral load, significantly fewer microscopic lesions in the intestinal tissue, and no diarrhea. These data show that chimeric APN is a promising strategy to combat PDCoV infection.

Pigs play important roles in agriculture and bio-medicine; however, porcine viral infections have caused huge losses to the pig industry and severely affected the animal welfare and social public safety. During viral infections, many non-coding RNAs are induced or repressed by viruses and regulate viral infection. Many viruses have, therefore, developed a number of mechanisms that use ncRNAs to evade the host immune system. Understanding how ncRNAs regulate host immunity during porcine viral infections is critical for the development of antiviral therapies. In this review, we provide a summary of the classification, production and function of ncRNAs involved in regulating porcine viral infections. Additionally, we outline pathways and modes of action by which ncRNAs regulate viral infections and highlight the therapeutic potential of artificial microRNA. Our hope is that this information will aid in the development of antiviral therapies based on ncRNAs for the pig industry.