Cellular entry of the porcine epidemic diarrhea virus.
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.
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Wentao
W
Li
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Frank J M
FJM
van Kuppeveld
State Key laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei province, China.
Qigai
Q
He
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Peter J M
PJM
Rottier
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Electronic address: b.j.bosch@uu.nl.
Berend-Jan
BJ
Bosch
D000818:Animals; D018352:Coronavirus Infections / Q000662:veterinary*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D053485:Porcine epidemic diarrhea virus / Q000502:physiology* / Q000648:ultrastructure; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine; D013553:Swine Diseases / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D053585:Virus Attachment
D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus; D019158:N-Acetylneuraminic Acid
Coronavirus; Membrane fusion; PED; PEDV; Porcine epidemic diarrhea virus; Proteolytic activation; Receptor interaction; Sialic acid; Sialic acid binding; Spike; Virus; Virus entry; Virus tropism