Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma.docVIP

Virology Journal BioMedCentral Research Open Access Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma Andrew E Firth*?1, Betty YW Chung?1, Marina N Fleeton?2 and John F Atkins*1,3 Address: 1BioSciences Institute, University College Cork, Cork, Ireland, 2Department of Microbiology, Moyne Institute for Preventive Medicine, Trinity College, Dublin 2, Ireland and 3Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA Email: Andrew E Firth* - A.Firth@ucc.ie; Betty YW Chung - B.Ying-WenChung@ucc.ie; Marina N Fleeton - fleetonm@tcd.ie; John F Atkins* - j.atkins@ucc.ie * Corresponding authors ?Equal contributors Published: 26 September 2008 Received: 27 August 2008 Accepted: 26 September 2008 Virology Journal 2008, 5:108 doi:10.1186/1743-422X-5-108 This article is available from: /content/5/1/108 ? 2008 Firth et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The genus Alphavirus includes several potentially lethal human viruses. Additionally, species such as Sindbis virus and Semliki Forest virus are important vectors for gene therapy, vaccination and cancer research, and important models for virion assembly and structural analyses. The genome encodes nine known proteins, including the small 6K protein. 6K appears to be involved in envelope protein processing, membrane permeabilization, virion assembly and virus budding. In protein gels, 6K migrates as a doublet – a result that, to date, has been attributed to differing degrees of acylation. Nonetheless, despite many years of research, its role is still relatively poorly understood. Results: We report that ribosomal -1 frameshifting, with an estimated efficiency of ~