Insights into bunyavirus architecture from electron cryotomography of Uukuniemi virus

doi:10.1073/pnas.0708738105

Insights into bunyavirus architecture from electron cryotomography of Uukuniemi virus

^†Ludwig Institute for Cancer Research, Stockholm Branch, Karolinska Institute, P.O. Box 240, S-17177 Stockholm, Sweden;
^§Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany; and
^¶Institute of Biotechnology, University of Helsinki, P.O. Box 65, FI-00014, Helsinki, Finland

Edited by Michael G. Rossmann, Purdue University, West Lafayette, IN, and approved December 21, 2007 (received for review September 14, 2007)

Abstract

Bunyaviridae is a large family of viruses that have gained attention as “emerging viruses” because many members cause serious disease in humans, with an increasing number of outbreaks. These negative-strand RNA viruses possess a membrane envelope covered by glycoproteins. The virions are pleiomorphic and thus have not been amenable to structural characterization using common techniques that involve averaging of electron microscopic images. Here, we determined the three-dimensional structure of a member of the Bunyaviridae family by using electron cryotomography. The genome, incorporated as a complex with the nucleoprotein inside the virions, was seen as a thread-like structure partially interacting with the viral membrane. Although no ordered nucleocapsid was observed, lateral interactions between the two membrane glycoproteins determine the structure of the viral particles. In the most regular particles, the glycoprotein protrusions, or “spikes,” were seen to be arranged on an icosahedral lattice, with T = 12 triangulation. This arrangement has not yet been proven for a virus. Two distinctly different spike conformations were observed, which were shown to depend on pH. This finding is reminiscent of the fusion proteins of alpha-, flavi-, and influenza viruses, in which conformational changes occur in the low pH of the endosome to facilitate fusion of the viral and host membrane during viral entry.

Footnotes

^‖To whom correspondence should be addressed. E-mail: huiskone{at}biochem.mpg.de
Author contributions: A.K.Ö., R.F.P., and J.T.H. designed research; A.K.Ö. and J.T.H. performed research; K.G. and J.T.H. analyzed data; and A.K.Ö., K.G., and J.T.H. wrote the paper.
↵ ^‡Present address: Department of Virology, Institute for Medical Microbiology and Hygiene, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0708738105/DC1.