Cellular entry of the porcine epidemic diarrhea virus

Abstract

Porcine epidemic diarrhea virus (PEDV), a coronavirus discovered more than 40 years ago, regained notoriety recently by its devastating outbreaks in East Asia and the Americas, causing substantial economic losses to the swine husbandry. The virus replicates extensively and almost exclusively in the epithelial cells of the small intestine resulting in villus atrophy, malabsorption and severe diarrhea. Cellular entry of this enveloped virus is mediated by the large spike (S) glycoprotein, trimers of which mediate virus attachment to the target cell and subsequent membrane fusion. The S protein has a multidomain architecture and has been reported to bind to carbohydrate (sialic acid) and proteinaceous (aminopeptidase N) cell surface molecules. PEDV propagation in vitro requires the presence of trypsin(-like) proteases in the culture medium, which capacitates the fusion function of the S protein. Here we review the current data on PEDV entry into its host cell, including therein our new observations regarding the functional role of the sialic acid binding activity of the S protein in virus infection. Moreover, we summarize the recent progress on the proteolytic activation of PEDV S proteins, and discuss factors that may determine tissue tropism of PEDV in vivo.

Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation

“…However, how the sialic acid binding activity affects the tropism of these alphacoronaviruses remains unclear. The S protein N-domain of some PEDV strains were thought to be dispensable for replication of PEDV in vitro [44–46]. The large deletions in the S protein of the PEDV variants in this study indicated that this domain might also be dispensable in vivo .…”

“…Besides, the mutant strain PC177-P2 can propagate well and induce diarrhea in piglets [43]. A deletion of 215 aa (position 19–233) in the N-terminal domain of the S protein analogous to the deletion observed in the variants revealed a not impaired propagation of PEDV in vivo [44]. Moreover, only variants with large S deletions were found in the field sample JAo-56, which indicated that the variants were able to independently propagate well in pigs.…”

“…Functions of the spike protein N-terminal domain of PEDV and other alphacoronaviruses were previously elucidated [44]. The loss of this domain occurred in a number of alphacoronaviruses correlates with a loss or reduction of enteric tropism.…”

“…FIPV is thought to be derived from FECV by natural mutation. However, compared to FECV, PIPV has a large deletion in the S protein N-domain which results in the loss of tropism for enterocytes [44, 45]. These examples revealed an important role of alphacoronavirus spike N-domain for viral replication in the enteric tract.…”

“…These examples revealed an important role of alphacoronavirus spike N-domain for viral replication in the enteric tract. The N-terminus (residues 1–249) of the S protein was demonstrated to be responsible for the sialic acid binding activity of PEDV [44]. The loss of enteric tropism observed in TGEV was specifically associated with the loss of the sialic binding activity that located in the N-domain.…”