Low-dose cadmium enhances coronavirus infectivity by amplifying viral receptor and suppressing goblet cell...

Emerging coronaviruses pose an escalating threat to human and animal health. Cadmium (Cd), a ubiquitous environmental toxic metal, accumulates in organisms due to its slow elimination rate. Despite its widespread presence, the impact of this non-infectious environmental factor on coronavirus pathogenicity remains poorly understood. Using porcine deltacoronavirus (PDCoV) as a model, we investigated the role of Cd in coronavirus infection, finding it exacerbates PDCoV infection in vivo, ex vivo, and in vitro. Mechanistically, Cd accumulation in intestinal epithelial cells enhances viral adhesion and invasion by damaging microvilli, disrupting tight junctions, and upregulating the aminopeptidase N (APN) expression, a key entry factor for PDCoV. Additionally, Cd suppresses intestinal stem cell differentiation into goblet cells by activating the Notch signalling pathway, exacerbating PDCoV-induced intestinal mucosal barrier dysfunction and promoting PDCoV infection. Collectively, our findings demonstrate that Cd potentiates coronavirus infectivity through a dual mechanism: upregulating viral receptor expression and disrupting intestinal mucosal integrity. This study provides mechanistic insights into how Cd exacerbates viral infection severity and informs public health strategies to mitigate coronavirus-associated morbidity and mortality.