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Journal of Virology, June 2008, p. 6045-6051, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.02392-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Site 1 Protease Is Required for Proteolytic Processing of the Glycoproteins of the South American Hemorrhagic Fever Viruses Junin, Machupo, and Guanarito{triangledown}

Jillian M. Rojek,1 Andrew M. Lee,1 NgocThao Nguyen,1 Christina F. Spiropoulou,2 and Stefan Kunz1,3*

Molecular and Integrative Neurosciences Department (MIND), The Scripps Research Institute, La Jolla, California 92037,1 Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,2 Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland3

Received 6 November 2007/ Accepted 28 March 2008

The cellular proprotein convertase site 1 protease (S1P) has been implicated in the proteolytic processing of the glycoproteins (GPs) of Old World arenaviruses. Here we report that S1P is also involved in the processing of the GPs of the genetically more-distant South American hemorrhagic fever viruses Guanarito, Machupo, and Junin. Efficient cleavage of Guanarito virus GP, whose protease recognition sites deviate from the reported S1P consensus sequence, indicates a broader specificity of S1P than anticipated. Lack of GP processing of Junin virus dramatically reduced production of infectious virus and prevented cell-to-cell propagation. Infection of S1P-deficient cells resulted in viral persistence over several weeks without the emergence of escape variants able to use other cellular proteases for GP processing.


* Corresponding author. Mailing address: Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne CH-1011, Switzerland. Phone: 41-21 314 7743. Fax: 41-21 314 4060. E-mail: Stefan.Kunz{at}chuv.ch

{triangledown} Published ahead of print on 9 April 2008.


Journal of Virology, June 2008, p. 6045-6051, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.02392-07
Copyright © 2008, 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]