Identification and Comparison of Receptor Binding Characteristics of the Spike Protein of Two Porcine Epidemic Diarrhea Virus Strains

Abstract

Porcine epidemic diarrhea virus (PEDV), a member of Alphacoronavirus, has caused huge economic losses for the global pork industry recently. The spike (S) protein mediates PEDV entry into host cells. Herein, we investigated the interactions between the S protein and its receptor porcine aminopeptidase N (pAPN) or co-receptor sugars. The C-terminal domain (CTD) of the S1 domain is bound to pAPN. The prototype strain demonstrated similar receptor-binding activity compared with the variant field isolate. Three loops at the tips of the β-barrel domains did not play crucial roles in the PEDV S-pAPN association, indicating that PEDV conforms to a different receptor recognition model compared with transmissible gastroenteritis virus (TGEV), porcine respiratory CoV (PRCV), and human coronavirus NL63 (HCoV-NL63). The N-terminal domain (NTD) of the PEDV S1 domain could bind sugar, a possible co-receptor for PEDV. The prototype strain exhibited weaker sugar-binding activity compared with the variant field isolate. Strategies targeting the receptor binding domain (RBD) may be helpful for developing vaccines or antiviral drugs for PEDV. Understanding the differences in receptor binding between the prototype and the variant strains may provide insight into PEDV pathogenesis.

Appearance of US-like porcine epidemic diarrhoea virus (PEDV) strains before US outbreaks and genetic heterogeneity of PEDVs collected in Northern Vietnam during 2012-2015

“…This indicated that VN297/HB/2013 might also possess the same 72‐nucleotide deletion in ORF1a compared with HUA‐14PED96, although more extensive genome sequencing is required to clarify this finding. In this study, we identified one novel PEDV strain, VN‐TH15/HY/2015, with an 8‐amino acid insertion between positions 380 and 381 of the S protein, which are located in the receptor‐binding domain (amino acids 253–638) for porcine aminopeptidase N (Liu et al., ; Deng et al., ). It is revealed that the classical PEDV exhibited weaker sugar‐binding activity than the recently uncovered G2 isolates (Deng et al., ).…”

“…In this study, we identified one novel PEDV strain, VN‐TH15/HY/2015, with an 8‐amino acid insertion between positions 380 and 381 of the S protein, which are located in the receptor‐binding domain (amino acids 253–638) for porcine aminopeptidase N (Liu et al., ; Deng et al., ). It is revealed that the classical PEDV exhibited weaker sugar‐binding activity than the recently uncovered G2 isolates (Deng et al., ). Amino acid substitutions were also reported in the receptor‐binding region (Wang et al., ).…”

Three Main Inducers of Alphacoronavirus Infection of Enterocytes: Sialic Acid, Proteases, and Low pH

“…Neu5Ac presented the highest binding affinity with PEDV S1 in experiments using a glycan array screening. Moreover, the sialic acid binding region of PEDV was confirmed as being in the NTD of the S protein (residues 1-320), similar to other CoVs [21]. However, it is unknown how the binding of sialic acid to the S protein can affect PEDV entry into cells.…”

“…Sequence analyses of PEDV prototype and variant strains reveal that the N terminus of the S protein changes more easily than the C terminus. In addition, a previous report suggested an interaction of NTD of the S1 domain with a coreceptor [20,21]. Simplified graphic of the structural domains of the main coronaviruses' spike proteins.…”

“…It is interesting that 3 receptor binding mutant proteins, RBM1-1, RBM2-1, and RBM3-2 proteins, did not significantly reduce PEDV pAPN-binding activities in virus infection [4], suggesting the PEDV S protein uses a receptor-binding mechanism different from TGEV and PRCoV. PEDV is further confirmed to have a broader receptor range than other α-CoVs [21].…”