Serial passage of PDCoV in cell culture reduces its pathogenicity and its damage of gut microbiota homeostasis in piglets

• DOI: 10.1128/msystems.01346-23
• Publication Date: 2024-02-13T14:02:51Z
• Authors: Yunfei Zhang; Lulu Si; Junlong Gao; Xiangli Shu; Congrui Qiu; Yue Zhang; Shaopo Zu; Hui Hu
• Keywords: Intestinal Permeability; Intestinal mucosa

ABSTRACT Porcine deltacoronavirus (PDCoV) is an enteropathogenic coronavirus that mainly causes diarrhea in suckling piglets, and also has the potential for cross-species transmission. However, there are still no commercial vaccines available to prevent control PDCoV infection. In this study, strain HNZK-02 was serially propagated vitro up 150 passages amino acid changes have occurred S protein during serial passage which caused structure change. HNZK-02-passage 5 (P5)-infected piglets exhibited acute severe watery diarrhea, obvious intestinal damage, while infected with HNZK-02-P150 showed clinical signs, weak lesions, lower viral loads rectal swabs various tissues. Compared HNZK-02-P5 infection, infection resulted a decrease mucosal permeability pro-inflammatory cytokines. Moreover, had significantly reduced bacterial diversity increased relative abundance of opportunistic pathogens, did not affect diversity, probiotics increased. Furthermore, alterations gut microbiota were closely related change factor. Metagenomics prediction analysis demonstrated modulated tyrosine metabolism, Nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, lipopolysaccharide biosynthesis, coincided inflammatory response HNZK-02-P150. conclusion, successfully attenuated by , gene, metabolic function, may contribute attenuation. The developing live-attenuated vaccine. IMPORTANCE enteropathogen causing dehydration, death nursing devastating great economic losses global swine industry, transmission zoonotic potential. There currently approved treatments or PDCoV. addition, important relationship development many diseases. Here, virulent on cell cultures, pathogenesis effects composition function P150 strains investigated piglets. We found genetic PDCoV, their interaction molecular mechanism would need be explored further.