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Journal of Virology, June 2002, p. 5993-6003, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.5993-6003.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Human Papillomavirus Type 31 Late 3' Untranslated Region Contains a Complex Bipartite Negative Regulatory Element

Sarah A. Cumming, Claire E. Repellin, Maria McPhillips, Jonathan C. Radford, J. Barklie Clements, and Sheila V. Graham*

Institute of Virology, University of Glasgow, Glasgow G11 5JR, Scotland

Received 21 November 2001/ Accepted 14 March 2002

The papillomavirus life cycle is tightly linked to epithelial cell differentiation. Production of virus capsid proteins is restricted to the most terminally differentiated keratinocytes in the upper layers of the epithelium. However, mRNAs encoding the capsid proteins can be detected in less-differentiated cells, suggesting that late gene expression is controlled posttranscriptionally. Short sequence elements (less than 80 nucleotides in length) that inhibit gene expression in undifferentiated epithelial cells have been identified in the late 3' untranslated regions (UTRs) of several papillomaviruses, including the high-risk mucosal type human papillomavirus type 16 (HPV-16). Here we show that closely related high-risk mucosal type HPV-31 also contains elements that can act to repress gene expression in undifferentiated epithelial cells. However, the HPV-31 negative regulatory element is surprisingly complex, comprising a major inhibitory element of approximately 130 nucleotides upstream of the late polyadenylation site and a minor element of approximately 110 nucleotides mapping downstream. The first 60 nucleotides of the major element have 68% identity to the negative regulatory element of HPV-16, and these elements bind the same cellular proteins, CstF-64, U2AF65, and HuR. The minor inhibitory element binds some cellular proteins in common with the major inhibitory element, though it also binds certain proteins that do not bind the upstream element.

* Corresponding author. Mailing address: Institute of Virology, University of Glasgow, Church St., Glasgow G11 5JR, Scotland. Phone: 44 141 330 6256. Fax: 44 141 337 2236. E-mail: s.v.graham{at}bio.gla.ac.uk.

Journal of Virology, June 2002, p. 5993-6003, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.5993-6003.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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