The N-terminal Region of the Porcine Epidemic Diarrhea Virus Spike Protein is Important for the Receptor Binding
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Porcine epidemic diarrhea virus (PEDV) infection causes acute enteritis with lethal watery diarrhea resulting in a high mortality rate in piglets. As with the other members of group 1 coronaviruses, PEDV also utilizes the host aminopeptidase N (APN) as the major cellular receptor for entry into target cells. The coronavirus spike (S) protein is known to interact with the cellular surface for viral attachment and the S1 domain of all characterized coronaviruses contains a receptor-binding domain (RBD) that mediates a specific high-affinity interaction with their respective cellular receptors. Although the RBDs of several coronaviruses have been mapped,the location of the PEDV RBD has to date not been defined. As a first step toward the identification of the region of the S protein of the PEDV that is critical for recognition with the cellular receptor, we generated a series of S1-truncated variants and examined their abilities to bind to the porcine APN (pAPN) receptor. Our data indicate that the N-terminus of the S1 domain is required for pAPN association. The results from the present study may assist in our understanding of the molecular interactions between the PEDV S protein and the pAPN receptor.
Abstract
Porcine epidemic diarrhea virus (PEDV) infection causes acute enteritis with lethal watery diarrhea resulting in a high mortality rate in piglets. As with the other members of group 1 coronaviruses, PEDV also utilizes the host aminopeptidase N (APN) as the major cellular receptor for entry into target cells. The coronavirus spike (S) protein is known to interact with the cellular surface for viral attachment and the S1 domain of all characterized coronaviruses contains a receptor-binding domain (RBD) that mediates a specific high-affinity interaction with their respective cellular receptors. Although the RBDs of several coronaviruses have been mapped,the location of the PEDV RBD has to date not been defined. As a first step toward the identification of the region of the S protein of the PEDV that is critical for recognition with the cellular receptor, we generated a series of S1-truncated variants and examined their abilities to bind to the porcine APN (pAPN) receptor. Our data indicate that the N-terminus of the S1 domain is required for pAPN association. The results from the present study may assist in our understanding of the molecular interactions between the PEDV S protein and the pAPN receptor.
참고문헌 (21)
- Bonavia, A., "Identification of a receptor-bindingdomain of the spike glycoprotein of human coronavirusHCoV-229E", J. Virol, 77, pp.530~538 (2002)
- Bosch, B. J., "The coronavirus spike protein is a class I virusfusion protein: structural and functional characterization ofthe fusion core complex", J. Virol, 77, pp.8801~8811 (2003)
- Delmas, B., "Aminopeptidase N is a majorreceptor for the entero-pathogenic coronavirus TGEV", Nature, 357, pp.417~420 (1992)
- Farzan M., "Tyrosine sulfation of the amino terminus ofCCR5 facilitates HIV-1 entry", Cell, 96, pp.667~676 (1999)
- Gallagher, T. M, "Coronavirusspike proteins in viral entry and pathogenesis", Virology, 279, pp.371~374 (2001)
- Godet, M., "Major receptor-binding and neutralization determinants arelocated within the same domain of the transmissible gastroenteritisvirus (coronavirus) spike protein", J. Virol, 68, pp.8008~8016 (1994)
- Kolb, A. F., "Siddell. 1998. Molecular analysis of the coronavirus-receptor function of aminopeptidase N", Adv. Exp. Med.Biol, 440, pp.61~67 (1998)
- Kubo, H., "Localizationof neutralizing epitopes and the receptor-binding site withinthe amino-terminal 330 amino acids of the murine coronavirusspike protein", J. Virol, 68, pp.403~410 (1994)
- Lai, C. C., "Proteomic analysis of up-regulatedproteins in human promonocyte cells expressing severeacute respiratory syndrome coronavirus 3C-like protease", Proteomics, 7, pp.1446~1460 (2007)
- Laude, H., "Functional domains in the spike protein ofransmissible gastroenteritis virus", Adv. Exp. Med. Biol, 380, pp.299~304 (1995)
- Lee, C., "ADNA-launched reverse genetics system for porcine reproductiveand respiratory syndrome virus reveals that homodimerizationof the nucleocapsid protein is essential for virusinfectivity", Virology, 331, pp.47~62 (2005)
- Lee, D. K., "Heterogeneityin spike protein genes of porcine epidemic diarrheaviruses isolated in Korea", Virus Res, 149, pp.175~182 (2010)
- Lee, Y. J., "Generation of a porcine alveolar macrophagecell line for the growth of porcine reproductive andrespiratory syndrome virus", J. Virol. Methods, 163, pp.410~415 (2010)
- Li, B. X., "Porcine aminopeptidaseN is a functional receptor for the PEDV coronavirus", Virology, 365, pp.166~172 (2007)
- Li, W., "Angiotensinconvertingenzyme 2 is a functional receptor for the SARScoronavirus", Nature, 426, pp.450~454 (2003)
- Lin, H. X., "Identification of residuesin the receptor-binding domain (RBD) of the spike protein ofhuman coronavirus NL63 that are critical for the RBD-ACE2receptor interaction", J. Gen. Virol, 89, pp.1015~1024 (2007)
- Nam, E, "Contribution of the porcine aminopeptidaseN (CD13) receptor density to porcine epidemicdiarrhea virus infection", Vet. Microbiol, 144, pp.41~50 (2010)
- Pensaert, M. B, "Porcine epidemic diarrhea", pp.367~372 (2006), Wiley-Blackwell
- Tresnan D. B., "Felineaminopeptidase N serves as a receptor for feline, canine,porcine, and human coronaviruses in serogroup I", J. Virol, 70, pp.669~674 (1996)
- Wong S. K., "A 193-amino acid fragment of the SARS coronavirusS protein efficiently binds angiotensin-converting enzyme 2", J. Biol. Chem, 279, pp.3197~3201 (2004)
- Yeager, C. L., "Human aminopeptidase N is a receptor for human coronavirus229E", Nature, 357, pp.420~422 (1992)