This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Google Scholar
Right arrow Articles by Madu, I. G.
Right arrow Articles by Whittaker, G. R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Madu, I. G.
Right arrow Articles by Whittaker, G. R.

 Previous Article  |  Next Article 

Journal of Virology, August 2009, p. 7411-7421, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00079-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Characterization of a Highly Conserved Domain within the Severe Acute Respiratory Syndrome Coronavirus Spike Protein S2 Domain with Characteristics of a Viral Fusion Peptide{triangledown}

Ikenna G. Madu, Shoshannah L. Roth, Sandrine Belouzard, and Gary R. Whittaker*

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853

Received 13 January 2009/ Accepted 6 May 2009

Many viral fusion proteins are primed by proteolytic cleavage near their fusion peptides. While the coronavirus (CoV) spike (S) protein is known to be cleaved at the S1/S2 boundary, this cleavage site is not closely linked to a fusion peptide. However, a second cleavage site has been identified in the severe acute respiratory syndrome CoV (SARS-CoV) S2 domain (R797). Here, we investigated whether this internal cleavage of S2 exposes a viral fusion peptide. We show that the residues immediately C-terminal to the SARS-CoV S2 cleavage site SFIEDLLFNKVTLADAGF are very highly conserved across all CoVs. Mutagenesis studies of these residues in SARS-CoV S, followed by cell-cell fusion and pseudotyped virion infectivity assays, showed a critical role for residues L803, L804, and F805 in membrane fusion. Mutation of the most N-terminal residue (S798) had little or no effect on membrane fusion. Biochemical analyses of synthetic peptides corresponding to the proposed S2 fusion peptide also showed an important role for this region in membrane fusion and indicated the presence of {alpha}-helical structure. We propose that proteolytic cleavage within S2 exposes a novel internal fusion peptide for SARS-CoV S, which may be conserved across the Coronaviridae.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Veterinary Medical Center, C4127, Cornell University, Ithaca NY 14853. Phone: (607) 253-4019. Fax: (607) 253-3385. E-mail: grw7{at}cornell.edu

{triangledown} Published ahead of print on 13 May 2009.

Journal of Virology, August 2009, p. 7411-7421, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00079-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Shulla, A., Gallagher, T. (2009). Role of Spike Protein Endodomains in Regulating Coronavirus Entry. J. Biol. Chem. 284: 32725-32734 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»