This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lobigs, M Articles by Garoff, H Search for Related Content PubMed PubMed Citation Articles by Lobigs, M Articles by Garoff, H

 Previous Article  |  Next Article 

J Virol. 1990 March; 64(3): 1233-1240

Fusion function of the Semliki Forest virus spike is activated by proteolytic cleavage of the envelope glycoprotein precursor p62.

Department of Molecular Biology, Karolinska Institute, Huddinge, Sweden.

ABSTRACT

The precursor protein p62 of the prototype alphavirus Semliki Forest virus (SFV) undergoes during transport to the cell surface a proteolytic cleavage to form the mature envelope glycoprotein E2. To investigate the biological significance of this cleavage event, single amino acid substitutions were introduced at the cleavages site through mutagenesis of cDNA corresponding to the structural region of the SFV genome. The phenotypes of the cleavage site mutants were studied in BHK cells by using recombinant vaccinia virus vectors. Nonconservative substitutions completely abolished p62 cleavage. Uncleaved p62 was transported with normal kinetics to the cell surface, where it became accessible to low concentrations of exogenous trypsin. The proteolytic cleavage of envelope glycoprotein precursors has been shown to activate the membrane fusion potential of viral spikes in several virus families. Here we demonstrate that the fusion function of the SFV spike is activated by the cleavage of p62. Cleavage-deficient p62 expressed at the cell surface did not function in low-pH-triggered (pH 5.5) cell-cell membrane fusion; however, cleavage of the mutated p62 with exogenous trypsin restored the fusion function. We discuss a model for SFV assembly and fusion where p62 cleavage plays a crucial role in the stability of the multimeric association of the viral envelope glycoproteins.

This article has been cited by other articles:

• Sjoberg, M., Lindqvist, B., Garoff, H. (2008). Stabilization of TM Trimer Interactions during Activation of Moloney Murine Leukemia Virus Env. J. Virol. 82: 2358-2366 [Abstract] [Full Text]  
• Maenz, C., Chang, S.-F., Iwanski, A., Bruns, M. (2007). Entry of Duck Hepatitis B Virus into Primary Duck Liver and Kidney Cells after Discovery of a Fusogenic Region within the Large Surface Protein. J. Virol. 81: 5014-5023 [Abstract] [Full Text]  
• Sjoberg, M., Wallin, M., Lindqvist, B., Garoff, H. (2006). Furin cleavage potentiates the membrane fusion-controlling intersubunit disulfide bond isomerization activity of leukemia virus env.. J. Virol. 80: 5540-5551 [Abstract] [Full Text]  
• Tscherne, D. M., Jones, C. T., Evans, M. J., Lindenbach, B. D., McKeating, J. A., Rice, C. M. (2006). Time- and Temperature-Dependent Activation of Hepatitis C Virus for Low-pH-Triggered Entry. J. Virol. 80: 1734-1741 [Abstract] [Full Text]  
• Elshuber, S., Mandl, C. W. (2005). Resuscitating Mutations in a Furin Cleavage-Deficient Mutant of the Flavivirus Tick-Borne Encephalitis Virus. J. Virol. 79: 11813-11823 [Abstract] [Full Text]  
• Krey, T., Thiel, H.-J., Rumenapf, T. (2005). Acid-Resistant Bovine Pestivirus Requires Activation for pH-Triggered Fusion during Entry. J. Virol. 79: 4191-4200 [Abstract] [Full Text]  
• Chanel-Vos, C., Kielian, M. (2004). A Conserved Histidine in the ij Loop of the Semliki Forest Virus E1 Protein Plays an Important Role in Membrane Fusion. J. Virol. 78: 13543-13552 [Abstract] [Full Text]  
• Okazaki, K., Kida, H. (2004). A synthetic peptide from a heptad repeat region of herpesvirus glycoprotein B inhibits virus replication. J. Gen. Virol. 85: 2131-2137 [Abstract] [Full Text]  
• Zhang, X., Fugere, M., Day, R., Kielian, M. (2003). Furin Processing and Proteolytic Activation of Semliki Forest Virus. J. Virol. 77: 2981-2989 [Abstract] [Full Text]  
• Elshuber, S., Allison, S. L., Heinz, F. X., Mandl, C. W. (2003). Cleavage of protein prM is necessary for infection of BHK-21 cells by tick-borne encephalitis virus. J. Gen. Virol. 84: 183-191 [Abstract] [Full Text]  
• Smit, J. M., Klimstra, W. B., Ryman, K. D., Bittman, R., Johnston, R. E., Wilschut, J. (2001). PE2 Cleavage Mutants of Sindbis Virus: Correlation between Viral Infectivity and pH-Dependent Membrane Fusion Activation of the Spike Heterodimer. J. Virol. 75: 11196-11204 [Abstract] [Full Text]  
• Smerdou, C., Liljeström, P. (1999). Two-Helper RNA System for Production of Recombinant Semliki Forest Virus Particles. J. Virol. 73: 1092-1098 [Abstract] [Full Text]  
• Glomb-Reinmund, S., Kielian, M. (1998). fus-1, a pH Shift Mutant of Semliki Forest Virus, Acts by Altering Spike Subunit Interactions via a Mutation in the E2 Subunit. J. Virol. 72: 4281-4287 [Abstract] [Full Text]  
• Tubulekas, I., Liljestrom, P. (1998). Suppressors of Cleavage-Site Mutations in the p62 Envelope Protein of Semliki Forest Virus Reveal Dynamics in Spike Structure and Function. J. Virol. 72: 2825-2831 [Abstract] [Full Text]  
• Yao, J., Strauss, E. G., Strauss, J. H. (1998). Molecular Genetic Study of the Interaction of Sindbis Virus E2 with Ross River Virus E1 for Virus Budding. J. Virol. 72: 1418-1423 [Abstract] [Full Text]  
• Chandran, K., Nibert, M. L. (1998). Protease Cleavage of Reovirus Capsid Protein µ1/µ1C Is Blocked by Alkyl Sulfate Detergents, Yielding a New Type of Infectious Subvirion Particle. J. Virol. 72: 467-475 [Abstract] [Full Text]