Abstract
Porcine deltacoronavirus (PDCoV), a member of genus Deltacoronavirus, is an emerging swine enteropathogenic coronavirus (CoV). Although outstanding efforts have led to the identification of Alphacoronavirus and Betacoronavirus receptors, the receptor for Deltacoronavirus is unclear. Here, we compared the amino acid sequences of several representative CoVs. Phylogenetic analysis showed that PDCoV spike (S) protein was close to the cluster containing transmissible gastroenteritis virus (TGEV), which utilizes porcine aminopeptidase N (pAPN) as a functional receptor. Ectopic expression of pAPN in non-susceptible BHK-21 cells rendered them susceptible to PDCoV. These results indicate that pAPN may be a functional receptor for PDCoV infection. However, treatment with APN-specific antibody and inhibitors did not completely block PDCoV infection in IPI-2I porcine intestinal epithelial cells. pAPN knockout in IPI-2I cells completely blocked TGEV infection but only slightly decreased PDCoV infection. Homologous modeling of pAPN with the S1 C-terminal domain (S1-CTD) of PDCoV or TGEV showed that TGEV S1-CTD adopted β-turns (β1–β2 and β3–β4), forming the tip of a β-barrel, to recognize pAPN. However, only the top residues in the β1–β2 turn of PDCoV S1-CTD had the possibility to support an interaction with pAPN, and the β3–β4 turn failed to contact pAPN. We also discuss the evolution and variation of PDCoV S1-CTD based on structure information, providing clues to explain the usage of pAPN by PDCoV. Taken together, the results presented herein reveal that pAPN is likely not a critical functional receptor for PDCoV, although it is involved in PDCoV infection.
Highlights
Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) belonging to the genus Deltacoronavirus of the family Coronaviridae within the order Nidovirales[1,2,3,4]
The different lengths of the two Discussion As an emerging swine enteropathogenic CoV and the sole member of the genus Deltacoronavirus that has been successfully isolated by cell culture in vitro, PDCoV is a good model to study deltacoronaviruses
A recent study showed that the β-sandwich core structure of PDCoV S1CTD, which may be responsible for receptor recognition, is similar to that of alphacoronaviruses, which mainly use APN as a cellular receptor[27]
Summary
Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) belonging to the genus Deltacoronavirus of the family Coronaviridae within the order Nidovirales[1,2,3,4]. Like other CoVs, PDCoV is an enveloped virus that contains positive, singlestranded genomic RNA5, 6. PDCoV was first identified in 2012 during molecular surveillance of CoVs in mammals and birds in Hong Kong[6]. The interaction between CoV spike (S) proteins and specific cellular receptors on host cell surfaces mediates viral attachment and fusion of viral and cellular membranes, playing a vital role in successful infection in the host[22,23,24]. The CoV S protein is a type I transmembrane glycoprotein with high molecular weight that protrudes from the surface of virions. Two research groups independently resolved the structure of PDCoV S protein by cryo-electron microscopy[26, 27]
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