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 Chanel-Vos, C.
Right arrow Articles by Kielian, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chanel-Vos, C.
Right arrow Articles by Kielian, M.

 Previous Article  |  Next Article 

Journal of Virology, December 2004, p. 13543-13552, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13543-13552.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Conserved Histidine in the ij Loop of the Semliki Forest Virus E1 Protein Plays an Important Role in Membrane Fusion

Chantal Chanel-Vos and Margaret Kielian*

Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York

Received 20 May 2004/ Accepted 19 August 2004

The enveloped alphavirus Semliki Forest virus (SFV) infects cells via a low pH-triggered membrane fusion reaction mediated by the E1 protein. E1 is a class II fusion protein that contains the hydrophobic fusion peptide loop and converts to a stable homotrimer during the fusion reaction. Intriguingly, the fusion loop is closely associated with a loop connecting the i and j ß-strands. This ij loop plays a role in the cholesterol dependence of membrane fusion and is specifically susceptible to proteolysis in the protease-resistant E1 homotrimer. The SFV ij loop contains a histidine residue at position 230. Sequence comparisons revealed that an analogous histidine is completely conserved in all alphavirus and flavivirus fusion proteins. An E1 H230A mutant was constructed using the SFV infectious clone. Although cells infected with H230A RNA produced virus particles, these virions were completely noninfectious and were blocked in both cell-cell fusion and lipid mixing assays. The H230A virions efficiently bound to cell surface receptors and responded to low pH by undergoing acid-dependent conformational changes including dissociation of the E1/E2 dimer, exposure of the fusion loop, association with target liposomes, exposure of acid-conformation-specific epitopes, and formation of the stable E1 homotrimer. Studies with a soluble fragment of E1 showed that the mutant protein was defective in lipid-dependent conformational changes. Our results indicate that the E1 ij loop and the conserved H230 residue play a critical role in alphavirus-membrane fusion and suggest the presence of a previously undescribed late intermediate in the fusion reaction.

* Corresponding author. Mailing address: Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-3638. Fax: (718) 430-8574. E-mail: kielian{at}aecom.yu.edu.

Journal of Virology, December 2004, p. 13543-13552, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13543-13552.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Qin, Z.-l., Zheng, Y., Kielian, M. (2009). Role of Conserved Histidine Residues in the Low-pH Dependence of the Semliki Forest Virus Fusion Protein. J. Virol. 83: 4670-4677 [Abstract] [Full Text]  
  • Fritz, R., Stiasny, K., Heinz, F. X. (2008). Identification of specific histidines as pH sensors in flavivirus membrane fusion. JCB 183: 353-361 [Abstract] [Full Text]  
  • Wu, S.-R., Haag, L., Hammar, L., Wu, B., Garoff, H., Xing, L., Murata, K., Cheng, R. H. (2007). The Dynamic Envelope of a Fusion Class II Virus: PREFUSION STAGES OF SEMLIKI FOREST VIRUS REVEALED BY ELECTRON CRYOMICROSCOPY. J. Biol. Chem. 282: 6752-6762 [Abstract] [Full Text]  
  • Nybakken, G. E., Nelson, C. A., Chen, B. R., Diamond, M. S., Fremont, D. H. (2006). Crystal Structure of the West Nile Virus Envelope Glycoprotein. J. Virol. 80: 11467-11474 [Abstract] [Full Text]  
  • Liao, M., Kielian, M. (2006). Functions of the Stem Region of the Semliki Forest Virus Fusion Protein during Virus Fusion and Assembly. J. Virol. 80: 11362-11369 [Abstract] [Full Text]  
  • Stiasny, K., Heinz, F. X. (2006). Flavivirus membrane fusion.. J. Gen. Virol. 87: 2755-2766 [Abstract] [Full Text]  
  • Chanel-Vos, C., Kielian, M. (2006). Second-Site Revertants of a Semliki Forest Virus Fusion-Block Mutation Reveal the Dynamics of a Class II Membrane Fusion Protein.. J. Virol. 80: 6115-6122 [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»