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 York, J.
Right arrow Articles by Nunberg, J. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by York, J.
Right arrow Articles by Nunberg, J. H.

 Previous Article  |  Next Article 

Journal of Virology, October 2004, p. 10783-10792, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10783-10792.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Signal Peptide of the Junín Arenavirus Envelope Glycoprotein Is Myristoylated and Forms an Essential Subunit of the Mature G1-G2 Complex

Joanne York,1 Victor Romanowski,2,3 Min Lu,4 and Jack H. Nunberg1*

Montana Biotechnology Center, The University of Montana, Missoula, Montana,1 Department of Biochemistry, Weill Medical College of Cornell University, New York, New York,4 Instituto de Bioquímica y Biología Molecular, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata,2 Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Bernal, Argentina3

Received 13 February 2004/ Accepted 26 April 2004

Arenaviruses comprise a diverse family of rodent-borne viruses that are responsible for recurring and emerging outbreaks of viral hemorrhagic fevers worldwide. The Junín virus, a member of the New World arenaviruses, is endemic to the pampas grasslands of Argentina and is the etiologic agent of Argentine hemorrhagic fever. In this study, we have analyzed the assembly and function of the Junín virus envelope glycoproteins. The mature envelope glycoprotein complex is proteolytically processed from the GP-C precursor polypeptide and consists of three noncovalently associated subunits, G1, G2, and a stable 58-amino-acid signal peptide. This tripartite organization is found both on virions of the attenuated Candid 1 strain and in cells expressing the pathogenic MC2 strain GP-C gene. Replacement of the Junín virus GP-C signal peptide with that of human CD4 has little effect on glycoprotein assembly while abolishing the ability of the G1-G2 complex to mediate pH-dependent cell-cell fusion. In addition, we demonstrate that the Junín virus GP-C signal peptide subunit is myristoylated at its N-terminal glycine. Alanine substitution for the modified glycine residue in the GP-C signal peptide does not affect formation of the tripartite envelope glycoprotein complex but markedly reduces its membrane fusion activity. In contrast to the classical view that signal peptides act primarily in targeting nascent polypeptides to the endoplasmic reticulum, we suggest that the signal peptide of the arenavirus GP-C may serve additional functions in envelope glycoprotein structure and trafficking.

* Corresponding author. Mailing address: Montana Biotechnology Center, The University of Montana, Missoula, MT 59812. Phone: (406) 243-6421. Fax: (406) 243-6425. E-mail: jack.nunberg{at}umontana.edu.

Journal of Virology, October 2004, p. 10783-10792, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10783-10792.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Albarino, C. G., Bergeron, E., Erickson, B. R., Khristova, M. L., Rollin, P. E., Nichol, S. T. (2009). Efficient Reverse Genetics Generation of Infectious Junin Viruses Differing in Glycoprotein Processing. J. Virol. 83: 5606-5614 [Abstract] [Full Text]  
  • York, J., Nunberg, J. H. (2009). Intersubunit Interactions Modulate pH-Induced Activation of Membrane Fusion by the Junin Virus Envelope Glycoprotein GPC. J. Virol. 83: 4121-4126 [Abstract] [Full Text]  
  • Larson, R. A., Dai, D., Hosack, V. T., Tan, Y., Bolken, T. C., Hruby, D. E., Amberg, S. M. (2008). Identification of a Broad-Spectrum Arenavirus Entry Inhibitor. J. Virol. 82: 10768-10775 [Abstract] [Full Text]  
  • York, J., Dai, D., Amberg, S. M., Nunberg, J. H. (2008). pH-Induced Activation of Arenavirus Membrane Fusion Is Antagonized by Small-Molecule Inhibitors. J. Virol. 82: 10932-10939 [Abstract] [Full Text]  
  • Lee, A. M., Rojek, J. M., Spiropoulou, C. F., Gundersen, A. T., Jin, W., Shaginian, A., York, J., Nunberg, J. H., Boger, D. L., Oldstone, M. B. A., Kunz, S. (2008). Unique Small Molecule Entry Inhibitors of Hemorrhagic Fever Arenaviruses. J. Biol. Chem. 283: 18734-18742 [Abstract] [Full Text]  
  • Rojek, J. M., Lee, A. M., Nguyen, N., Spiropoulou, C. F., Kunz, S. (2008). Site 1 Protease Is Required for Proteolytic Processing of the Glycoproteins of the South American Hemorrhagic Fever Viruses Junin, Machupo, and Guanarito. J. Virol. 82: 6045-6051 [Abstract] [Full Text]  
  • Dultz, E., Hildenbeutel, M., Martoglio, B., Hochman, J., Dobberstein, B., Kapp, K. (2008). The Signal Peptide of the Mouse Mammary Tumor Virus Rem Protein Is Released from the Endoplasmic Reticulum Membrane and Accumulates in Nucleoli. J. Biol. Chem. 283: 9966-9976 [Abstract] [Full Text]  
  • York, J., Nunberg, J. H. (2007). A Novel Zinc-Binding Domain Is Essential for Formation of the Functional Junin Virus Envelope Glycoprotein Complex. J. Virol. 81: 13385-13391 [Abstract] [Full Text]  
  • Schrempf, S., Froeschke, M., Giroglou, T., von Laer, D., Dobberstein, B. (2007). Signal Peptide Requirements for Lymphocytic Choriomeningitis Virus Glycoprotein C Maturation and Virus Infectivity. J. Virol. 81: 12515-12524 [Abstract] [Full Text]  
  • Rojek, J. M., Campbell, K. P., Oldstone, M. B.A., Kunz, S. (2007). Old World Arenavirus Infection Interferes with the Expression of Functional {alpha}-Dystroglycan in the Host Cell. Mol. Biol. Cell 18: 4493-4507 [Abstract] [Full Text]  
  • Hebert, D. N., Molinari, M. (2007). In and Out of the ER: Protein Folding, Quality Control, Degradation, and Related Human Diseases. Physiol. Rev. 87: 1377-1408 [Abstract] [Full Text]  
  • Capul, A. A., Perez, M., Burke, E., Kunz, S., Buchmeier, M. J., de la Torre, J. C. (2007). Arenavirus Z-Glycoprotein Association Requires Z Myristoylation but Not Functional RING or Late Domains. J. Virol. 81: 9451-9460 [Abstract] [Full Text]  
  • Klewitz, C., Klenk, H.-D., ter Meulen, J. (2007). Amino acids from both N-terminal hydrophobic regions of the Lassa virus envelope glycoprotein GP-2 are critical for pH-dependent membrane fusion and infectivity. J. Gen. Virol. 88: 2320-2328 [Abstract] [Full Text]  
  • Martinez, M. G., Cordo, S. M., Candurra, N. A. (2007). Characterization of Junin arenavirus cell entry. J. Gen. Virol. 88: 1776-1784 [Abstract] [Full Text]  
  • Saunders, A. A., Ting, J. P. C., Meisner, J., Neuman, B. W., Perez, M., de la Torre, J. C., Buchmeier, M. J. (2007). Mapping the Landscape of the Lymphocytic Choriomeningitis Virus Stable Signal Peptide Reveals Novel Functional Domains. J. Virol. 81: 5649-5657 [Abstract] [Full Text]  
  • Agnihothram, S. S., York, J., Trahey, M., Nunberg, J. H. (2007). Bitopic Membrane Topology of the Stable Signal Peptide in the Tripartite Junin Virus GP-C Envelope Glycoprotein Complex. J. Virol. 81: 4331-4337 [Abstract] [Full Text]  
  • York, J., Nunberg, J. H. (2006). Role of the Stable Signal Peptide of Junin Arenavirus Envelope Glycoprotein in pH-Dependent Membrane Fusion.. J. Virol. 80: 7775-7780 [Abstract] [Full Text]  
  • Agnihothram, S. S., York, J., Nunberg, J. H. (2006). Role of the stable signal Peptide and cytoplasmic domain of g2 in regulating intracellular transport of the junin virus envelope glycoprotein complex.. J. Virol. 80: 5189-5198 [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»