Porcine epidemic diarrhoea virus (PEDV) is a highly contagious enteric coronavirus causing acute watery diarrhoea and high mortality in neonatal piglets, threatening the global swine industry. In recent years, GIIc subtype PEDV has spread rapidly across China via natural recombination and antigenic drift, undermining conventional vaccine efficacy. Here, we isolated and characterized a novel GIIc PEDV strain CHjx2025 from diarrheic piglets in Ji'an City, Jiangxi Province, China. Full-length genome sequencing and recombination analysis identified CHjx2025 as a natural intra-lineage recombinant of two GIIc strains (CH-JXJA-2017 as major parent and CH-SWM-RN-2025 as minor parent), with a recombination breakpoint at nucleotide 11,201 of ORF1a. Comparative analysis revealed 49 unique amino acid substitutions in the spike (S) protein core region relative to the classic vaccine strain CV777, including 10 in the core receptor-binding domain (COE) and 1 in the 2C10 neutralizing epitope. Structural modeling confirmed CHjx2025 retains a canonical homotrimeric type I fusion protein structure but exhibits distinct NTD and D0 domains versus CV777. In vitro, CHjx2025 showed strong replicative capacity, forming larger plaques and reaching 106.5TCID50/mL in Vero cells at 24 hpi. Notably, in vivo challenge induced vomiting and anorexia in neonatal piglets as early as 12 hpi, with 100% mortality within 60 h, severe intestinal villous atrophy, and unprecedented multinucleated syncytia in intestinal epithelial cells. These findings highlight the evolving diversity and enhanced pathogenicity of GIIc PEDV via intra-subtype recombination and epitope mutations, underscoring the need for continuous surveillance and GIIc-specific vaccine development to control PED outbreaks.
Jinpeng Fan, Yan-ling Liu, Wenqian Fu et al.· BMC Veterinary Research· 1 citation· ⚡1
ABSTRACT Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that causes severe diarrhea, vomiting, and dehydration in piglets, and a recent human infection report raises concerns about its zoonotic potential. The S1 subunit of the PDCoV-spike protein is the primary target of neutralizing antibodies and is critical for viral attachment and entry. In this study, we generated and characterized eight monoclonal antibodies (mAbs) against S1, two targeting the S1A domain, five targeting the S1B domain, and one binding the S1C domain. Using a genetically engineered luciferase reporter virus, we demonstrated that all five S1B-targeting mAbs neutralize viral infection by disrupting S1-aminopeptidase N receptor engagement. These S1B mAbs cross-react with S1B proteins from multiple human- and avian-origin deltacoronaviruses, suggesting the recognition of conserved antigenic regions. Importantly, we found that our PDCoV strain caused embryo lethality in embryonated chicken eggs (ECEs). Using this ECE lethal model, we performed a preliminary in vivo evaluation of the five S1B-specific neutralizing mAbs. All five mAbs improved embryo survival, with 3E9 providing complete protection against PDCoV-induced embryonic lethality. Collectively, these novel mAbs represent valuable tools for diagnosis and therapeutic development. Moreover, the luciferase-reporter virus and the ECE model establish robust platforms for future evaluation of neutralizing antibodies against PDCoV. IMPORTANCE Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that threatens swine health and poses a potential risk of cross-species transmission; however, effective countermeasures remain limited. We generated and characterized a panel of monoclonal antibodies targeting the PDCoV S1 protein and identified five S1B-specific neutralizing antibodies that cross-react with S1B proteins from multiple human- and avian-origin deltacoronavirusess. We also established complementary in vitro and preliminary in vivo platforms for antibody evaluation using a firefly luciferase reporter virus and an embryonated chicken egg model. Together, these findings expand the repertoire of PDCoV-neutralizing antibodies and provide practical tools for antibody characterization and preliminary protective efficacy assessment, facilitating future studies on antibody-based interventions against emerging deltacoronaviruses. Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that threatens swine health and poses a potential risk of cross-species transmission; however, effective countermeasures remain limited. We generated and characterized a panel of monoclonal antibodies targeting the PDCoV S1 protein and identified five S1B-specific neutralizing antibodies that cross-react with S1B proteins from multiple human- and avian-origin deltacoronavirusess. We also established complementary in vitro and preliminary in vivo platforms for antibody evaluation using a firefly luciferase reporter virus and an embryonated chicken egg model. Together, these findings expand the repertoire of PDCoV-neutralizing antibodies and provide practical tools for antibody characterization and preliminary protective efficacy assessment, facilitating future studies on antibody-based interventions against emerging deltacoronaviruses.
Jiaru Zhou, Ran Jing, Mengdi Zhang et al.· mBio· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
