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Journal of Virology, August 2002, p. 7407-7417, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7407-7417.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

pH Reduction as a Trigger for Dissociation of Herpes Simplex Virus Type 1 Scaffolds

David A. McClelland,1 James D. Aitken,2 David Bhella,1 David McNab,1 Joyce Mitchell,1 Sharon M. Kelly,3 Nicholas C. Price,3 and Frazer J. Rixon1*

MRC Virology Unit,1 Division of Virology,2 Division of Biochemistry and Molecular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Scotland, United Kingdom3

Received 1 February 2002/ Accepted 24 April 2002

Assembly of the infectious herpes simplex virus type 1 virion is a complex, multistage process that begins with the production of a procapsid, which is formed by the condensation of capsid shell proteins around an internal scaffold fashioned from multiple copies of the scaffolding protein, pre-VP22a. The ability of pre-VP22a to interact with itself is an essential feature of this process. However, this self-interaction must subsequently be reversed to allow the scaffolding proteins to exit from the capsid to make room for the viral genome to be packaged. The nature of the process by which dissociation of the scaffold is accomplished is unknown. Therefore, to investigate this process, the properties of isolated scaffold particles were investigated. Electron microscopy and gradient sedimentation studies showed that the particles could be dissociated by low concentrations of chaotropic agents and by moderate reductions in pH (from 7.2 to 5.5). Fluorescence spectroscopy and circular dichroism analyses revealed that there was relatively little change in tertiary and secondary structures under these conditions, indicating that major structural transformations are not required for the dissociation process. We suggest the possibility that dissociation of the scaffold may be triggered by a reduction in pH brought about by the entry of the viral DNA into the capsid.

* Corresponding author. Mailing address: MRC Virology Unit, Institute of Virology, Church St., Glasgow G11 5JR, United Kingdom. Phone: 44 141 330 4025. Fax: 44 141 337 2236. E-mail: f.rixon{at}vir.gla.ac.uk.

Journal of Virology, August 2002, p. 7407-7417, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7407-7417.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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