Abstract:

Porcine reproductive and respiratory syndrome (PRRS), also known as blue-ear disease, is a major infectious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV) and poses a severe threat to the global swine industry. Due to the complex immune evasion mechanisms and high mutation rate of PRRSV, traditional vaccine-based prevention and control strategies often fail to achieve the desired efficacy. Breeding genetically resistant pig lines is therefore critical for controlling the disease at its source. Gene editing technologies, characterized by their ability to precisely target specific genomic loci, have effectively overcome the long cycles and low efficiency that plague conventional breeding approaches, thereby offering a highly efficient route for PRRS resistance breeding. Porcine CD163 has been identified as an indispensable key receptor for PRRSV infection of host target cells. Consequently, precise editing of the CD163 gene and the creation of disease-resistant germplasm have emerged as highly competitive frontiers in swine genetics internationally. This review systematically summarizes the structural characteristics and physiological functions of the CD163 receptor and comprehensively traces the development of gene editing technologies used to generate PRRS-resistant pigs. Current research indicates that targeting strategies are evolving from early imprecise disruptions toward precise modifications of critical structural domains. This paradigm shift has successfully conferred PRRS resistance in pigs while largely preserving the core physiological functions of CD163. Addressing the limitations of current technologies and the practical needs of the swine industry, this review further discusses key directions for future breakthroughs. First, precise single-amino-acid substitution using base editing technology represents a major future trend; however, overcoming the bystander effect and off-target risks through rational engineering of deaminases and AI-based prediction of cryptic splice sites is urgently needed. Second, given the pressure from multi-pathogen co-infections and the presence of additional accessory receptors for PRRSV, targeting CD163 alone has inherent limitations. Therefore, exploring multiplex synergistic editing of CD163 alongside other receptor genes or economically relevant traits is an inevitable necessity. Finally, catalyzed by breakthrough international regulatory approvals (e.g., from the US FDA) and the ongoing refinement of biosafety evaluation guidelines in China, gene-edited PRRS-resistant pigs are steadily advancing toward commercial application, demonstrating vast industrialization prospects. Ultimately, this review aims to provide theoretical support and forward-looking references for the precision breeding of novel pig lines with broad-spectrum and durable disease resistance.

Key words: CD163 receptor, porcine reproductive and respiratory syndrome virus, gene editing, disease-resistant breeding, pig