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
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rawling, J.
Right arrow Articles by Melero, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rawling, J.
Right arrow Articles by Melero, J. A.

 Previous Article  |  Next Article 

Journal of Virology, June 2008, p. 5986-5998, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.00078-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Insertion of the Two Cleavage Sites of the Respiratory Syncytial Virus Fusion Protein in Sendai Virus Fusion Protein Leads to Enhanced Cell-Cell Fusion and a Decreased Dependency on the HN Attachment Protein for Activity{triangledown}

Joanna Rawling, Blanca García-Barreno, and José A. Melero*

Biología Viral, Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain

Received 12 January 2008/ Accepted 24 March 2008

Cell entry by paramyxoviruses requires fusion of the viral envelope with the target cell membrane. Fusion is mediated by the viral fusion (F) glycoprotein and usually requires the aid of the attachment glycoprotein (G, H or HN, depending on the virus). Human respiratory syncytial virus F protein (FRSV) is able to mediate membrane fusion in the absence of the attachment G protein and is unique in possessing two multibasic furin cleavage sites, separated by a region of 27 amino acids (pep27). Cleavage at both sites is required for cell-cell fusion. We have investigated the significance of the two cleavage sites and pep27 in the context of Sendai virus F protein (FSeV), which possesses a single monobasic cleavage site and requires both coexpression of the HN attachment protein and trypsin in order to fuse cells. Inclusion of both FRSV cleavage sites in FSeV resulted in a dramatic increase in cell-cell fusion activity in the presence of HN. Furthermore, chimeric FSeV mutants containing both FRSV cleavage sites demonstrated cell-cell fusion in the absence of HN. The presence of two multibasic cleavage sites may therefore represent a strategy to regulate activation of a paramyxovirus F protein for cell-cell fusion in the absence of an attachment protein.

* Corresponding author. Mailing address: Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain. Phone: 34 91 5097941. Fax: 34 91 5097918. E-mail: jmelero{at}isciii.es

{triangledown} Published ahead of print on 2 April 2008.

Journal of Virology, June 2008, p. 5986-5998, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.00078-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • de Graaf, M., Schrauwen, E. J. A., Herfst, S., van Amerongen, G., Osterhaus, A. D. M. E., Fouchier, R. A. M. (2009). Fusion protein is the main determinant of metapneumovirus host tropism. J. Gen. Virol. 90: 1408-1416 [Abstract] [Full Text]  
  • Belouzard, S., Chu, V. C., Whittaker, G. R. (2009). Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc. Natl. Acad. Sci. USA 106: 5871-5876 [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»