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Journal of Virology, September 2009, p. 8482-8491, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00660-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Impact of Quaternary Organization on the Antigenic Structure of the Tick-Borne Encephalitis Virus Envelope Glycoprotein E{triangledown} ,{dagger}

Stefan Kiermayr, Karin Stiasny, and Franz X. Heinz*

Institute of Virology, Medical University of Vienna, Kinderspitalgasse 15, A-1095 Vienna, Austria

Received 31 March 2009/ Accepted 8 June 2009

The envelope protein E of flaviviruses mediates both receptor-binding and membrane fusion. At the virion surface, 180 copies of E are tightly packed and organized in a herringbone-like icosahedral structure, whereas in noninfectious subviral particles, 60 copies are arranged in a T=1 icosahedral symmetry. In both cases, the basic building block is an E dimer which exposes the binding sites for neutralizing antibodies at its surface. It was the objective of our study to assess the dependence of the antigenic structure of E on its quaternary arrangement, i.e., as part of virions, recombinant subviral particles, or soluble dimers. For this purpose, we used a panel of 11 E protein-specific neutralizing monoclonal antibodies, mapped to distinct epitopes in each of the three E protein domains, and studied their reactivity with the different soluble and particulate forms of tick-borne encephalitis virus E protein under nondenaturing immunoassay conditions. Significant differences in the reactivities with these forms were observed that could be related to (i) limited access of certain epitopes at the virion surface; (ii) limited occupancy of epitopes in virions due to steric hindrance between antibodies; (iii) differences in the avidity to soluble forms compared to the virion, presumably related to the flexibility of E at its domain junctions; and (iv) modulations of the external E protein surface through interactions with its stem-anchor structure. We have thus identified several important factors that influence the antigenicity of the flavivirus E protein and have an impact on the interaction with neutralizing antibodies.

* Corresponding author. Mailing address: Institute of Virology, Medical University of Vienna, Kinderspitalgasse 15, A-1095 Vienna, Austria. Phone: 43 1 40490 79510. Fax: 43 1 40490 9795. E-mail: franz.x.heinz{at}meduniwien.ac.at

{triangledown} Published ahead of print on 24 June 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, September 2009, p. 8482-8491, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00660-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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