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 Meulendyke, K. A.
Right arrow Articles by Dutch, R. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meulendyke, K. A.
Right arrow Articles by Dutch, R. E.

 Previous Article  |  Next Article 

Journal of Virology, October 2005, p. 12643-12649, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12643-12649.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Endocytosis Plays a Critical Role in Proteolytic Processing of the Hendra Virus Fusion Protein

Kelly Ann Meulendyke, Mark Allen Wurth, Richard O. McCann, and Rebecca Ellis Dutch*

Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536-0298

Received 10 May 2005/ Accepted 20 July 2005

The Hendra virus fusion (F) protein is synthesized as a precursor protein, F0, which is proteolytically processed to the mature form, F1+F2. Unlike the case for the majority of paramyxovirus F proteins, the processing event is furin independent, does not require the addition of exogenous proteases, is not affected by reductions in intracellular Ca2+, and is strongly affected by conditions that raise the intracellular pH (C. T. Pager, M. A. Wurth, and R. E. Dutch, J. Virol. 78:9154-9163, 2004). The Hendra virus F protein cytoplasmic tail contains a consensus motif for endocytosis, YXX{Phi}. To analyze the potential role of endocytosis in the processing and membrane fusion promotion of the Hendra virus F protein, mutation of tyrosine 525 to alanine (Hendra virus F Y525A) or phenylalanine (Hendra virus F Y525F) was performed. The rate of endocytosis of Hendra virus F Y525A was significantly reduced compared to that of the wild-type (wt) F protein, confirming the functional importance of the endocytosis motif. An intermediate level of endocytosis was observed for Hendra virus F Y525F. Surprisingly, dramatic reductions in the rate of proteolytic processing were observed for Hendra virus F Y525A, although initial transport to the cell surface was not affected. The levels of surface expression for both Hendra virus F Y525A and Hendra virus F Y525F were higher than that of the wt protein, and these mutants displayed enhanced syncytium formation. These results suggest that endocytosis is critically important for Hendra virus F protein cleavage, representing a new paradigm for proteolytic processing of paramyxovirus F proteins.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 741 S. Limestone, BBSRB, Lexington, KY 40536-0509. Phone: (859) 323-1795. Fax: (859) 323-1037. E-mail: rdutc2{at}uky.edu.

Journal of Virology, October 2005, p. 12643-12649, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12643-12649.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tsurudome, M., Nishio, M., Ito, M., Tanahashi, S., Kawano, M., Komada, H., Ito, Y. (2008). Effects of Hemagglutinin-Neuraminidase Protein Mutations on Cell-Cell Fusion Mediated by Human Parainfluenza Type 2 Virus. J. Virol. 82: 8283-8295 [Abstract] [Full Text]  
  • Gardner, A. E., Dutch, R. E. (2007). A Conserved Region in the F2 Subunit of Paramyxovirus Fusion Proteins Is Involved In Fusion Regulation. J. Virol. 81: 8303-8314 [Abstract] [Full Text]  
  • Aguilar, H. C., Matreyek, K. A., Choi, D. Y., Filone, C. M., Young, S., Lee, B. (2007). Polybasic KKR Motif in the Cytoplasmic Tail of Nipah Virus Fusion Protein Modulates Membrane Fusion by Inside-Out Signaling. J. Virol. 81: 4520-4532 [Abstract] [Full Text]  
  • Cantin, C., Holguera, J., Ferreira, L., Villar, E., Munoz-Barroso, I. (2007). Newcastle disease virus may enter cells by caveolae-mediated endocytosis. J. Gen. Virol. 88: 559-569 [Abstract] [Full Text]  
  • Ciancanelli, M. J., Basler, C. F. (2006). Mutation of YMYL in the Nipah Virus Matrix Protein Abrogates Budding and Alters Subcellular Localization. J. Virol. 80: 12070-12078 [Abstract] [Full Text]  
  • Porotto, M., Doctor, L., Carta, P., Fornabaio, M., Greengard, O., Kellogg, G. E., Moscona, A. (2006). Inhibition of Hendra Virus Fusion. J. Virol. 80: 9837-9849 [Abstract] [Full Text]  
  • Pager, C. T., Dutch, R. E. (2005). Cathepsin L Is Involved in Proteolytic Processing of the Hendra Virus Fusion Protein. J. Virol. 79: 12714-12720 [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»