Abstract
With the emergence of highly pathogenic variant strains, porcine epidemic diarrhea virus (PEDV) has led to significant economic loss in the global swine industry. Many studies have described how coronaviruses enter cells, but information on PEDV invasion strategies remains insufficient. Given that the differences in gene sequences and pathogenicity between classical and mutant strains of PEDV may lead to diverse invasion mechanisms, this study focused on the cellular entry pathways and cellular transport of the PEDV GI and GII subtype strains in Vero cells and IPEC-J2 cells. We first characterized the kinetics of PEDV entry into cells and found that the highest invasion rate of PEDV was approximately 33% in the IPEC-J2 cells and approximately 100% in the Vero cells. To clarify the specific endocytic pathways, systematic research methods were used and showed that PEDV enters cells via the clathrin- and caveolae-mediated endocytosis pathways, in which dynamin II, clathrin heavy chain, Eps15, cholesterol, and caveolin-1 were indispensably involved. In addition, lipid raft extraction assay showed that PEDV can also enter cells through lipid raft-mediated endocytosis. To investigate the trafficking of internalized PEDV, we found that PEDV entry into cells relied on low pH and internalized virions reached lysosomes through the early endosome–late endosome–lysosome pathway. The results concretely revealed the entry mechanisms of PEDV and provided an insightful theoretical basis for the further understanding of PEDV pathogenesis and guidance for new targets of antiviral drugs.
Highlights
As a type of alphacoronavirus, porcine epidemic diarrhea virus (PEDV) has caused enormous economic loss to the global pork industry, especially after the emergence of highly pathogenic PEDV variant strains in 2010
When viral particles interact with receptors, caveolae coated with caveolin-1 invaginates and pinches off plasma membrane, the caveolae vesicles mature into caveosomes and deliver “cargoes” to early endosomes [20, 21]
Many studies have reported that vaccines based on CV777 or CV777-like strains have low protection efficiency against re-emerging variant strains [3, 4, 6,7,8]
Summary
As a type of alphacoronavirus, porcine epidemic diarrhea virus (PEDV) has caused enormous economic loss to the global pork industry, especially after the emergence of highly pathogenic PEDV variant strains in 2010. The endocytic pathways utilized by viruses vary, including clathrin-mediated endocytosis (CME), caveolaemediated endocytosis, lipid raft-mediated endocytosis, Wei et al Vet Res (2020) 51:10 and macropinocytosis, among others. After binding to cell surface receptors, the virus is packaged by clathrin-coated pits (CCPs) and transported to clathrin-coated vesicles (CCVs), in which virus particles as the “cargo” will be transported to the early endosomes [18, 19]. When viral particles interact with receptors, caveolae coated with caveolin-1 invaginates and pinches off plasma membrane, the caveolae vesicles mature into caveosomes and deliver “cargoes” to early endosomes [20, 21]. Lipid raft are plasma membrane microdomains enriched in sphingolipids and cholesterol that participate in the lateral organization of the cell surface. Raft-mediated endocytosis is the process of internalization of ligands and receptors by these domains [22]
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