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Journal of Virology, December 2009, p. 12101-12107, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01637-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Association of the pr Peptides with Dengue Virus at Acidic pH Blocks Membrane Fusion{triangledown}

I.-M. Yu,1,{dagger} H. A. Holdaway,1 P. R. Chipman,1 R. J. Kuhn,1 M. G. Rossmann,1 and J. Chen1,2*

Department of Biological Sciences, Purdue University,1 Howard Hughes Medical Institute, 915 W. State Street, West Lafayette, Indiana 479072

Received 5 August 2009/ Accepted 8 September 2009

Flavivirus assembles into an inert particle that requires proteolytic activation by furin to enable transmission to other hosts. We previously showed that immature virus undergoes a conformational change at low pH that renders it accessible to furin (I. M. Yu, W. Zhang, H. A. Holdaway, L. Li, V. A. Kostyuchenko, P. R. Chipman, R. J. Kuhn, M. G. Rossmann, and J. Chen, Science 319:1834-1837, 2008). Here we show, using cryoelectron microscopy, that the structure of immature dengue virus at pH 6.0 is essentially the same before and after the cleavage of prM. The structure shows that after cleavage, the proteolytic product pr remains associated with the virion at acidic pH, and that furin cleavage by itself does not induce any major conformational changes. We also show by liposome cofloatation experiments that pr retention prevents membrane insertion, suggesting that pr is present on the virion in the trans-Golgi network to protect the progeny virus from fusion within the host cell.

* Corresponding author. Mailing address: 915 W. State St., West Lafayette, IN 47907. Phone: (765) 496-3113. Fax: (765) 496-1189. E-mail: chenjue{at}purdue.edu

{triangledown} Published ahead of print on 16 September 2009.

{dagger} Present address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

Journal of Virology, December 2009, p. 12101-12107, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01637-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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