biostudies-literatureFeng ZNatural Science Foundation of Fujian ProvinceNational Natural Science Foundation of China136https://www.ebi.ac.uk/biostudies/studies/S-EPMC11965083biostudies-literatureUnknown82(1)Porcine epidemic diarrhea virus (PEDV) has caused significant losses in the pork industry, but the mechanism of PEDV infection is still unclear. On the basis of our RNA-Seq data and due to the potential role of sialic acid as a coreceptor, we investigated the function of sialic acid-binding Ig-like lectin 15 (Siglec-15) to determine its role as a receptor in PEDV infection. We found that Siglec-15 enhances PEDV infection by promoting viral adsorption to host cells. Coimmunoprecipitation and immunofluorescence assays revealed that Siglec-15 binds to the S1 subunit and M protein of PEDV. PEDV infectivity was significantly reduced in Siglec-15 knockout mice. In addition, we developed a monoclonal antibody targeting Siglec-15 that can effectively inhibit PEDV infection both in vitro and in vivCellular and molecular life sciences : CMLSSiglec-15 is a putative receptor for porcine epidemic diarrhea virus infection.PMC1196508382350126821719912022J01652Chen QFeng ZChen JFu YLi ZHuang WHe XChen YLiu CShen YYang SLin MZhao HfalseSiglec-15 is a putative receptor for porcine epidemic diarrhea virus infection.Porcine epidemic diarrhea virus (PEDV) has caused significant losses in the pork industry, but the mechanism of PEDV infection is still unclear. On the basis of our RNA-Seq data and due to the potential role of sialic acid as a coreceptor, we investigated the function of sialic acid-binding Ig-like lectin 15 (Siglec-15) to determine its role as a receptor in PEDV infection. We found that Siglec-15 enhances PEDV infection by promoting viral adsorption to host cells. Coimmunoprecipitation and immunofluorescence assays revealed that Siglec-15 binds to the S1 subunit and M protein of PEDV. PEDV infectivity was significantly reduced in Siglec-15 knockout mice. In addition, we developed a monoclonal antibody targeting Siglec-15 that can effectively inhibit PEDV infection both in vitro and in viv2025-01-01T00:00:00Z2025 Apr2026-06-01T05:40:33.823Z2025-07-12T03:04:21.237ZS-EPMC119650834017266010.1007/s00018-025-05672-2