Association of the pr peptides with dengue virus at acidic pH blocks membrane fusion

J Virol. 2009 Dec;83(23):12101-7. doi: 10.1128/JVI.01637-09. Epub 2009 Sep 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cryoelectron Microscopy
  • Culicidae
  • Dengue Virus / physiology*
  • Dengue Virus / ultrastructure
  • Furin / metabolism*
  • Hydrogen-Ion Concentration
  • Image Processing, Computer-Assisted
  • Models, Biological
  • Models, Molecular
  • Virus Assembly*
  • Virus Internalization*

Substances

  • Furin