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Journal of Virology, October 2002, p. 9702-9715, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9702-9715.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Upstream Regulatory Region of Human Papillomavirus Type 31 Is Insensitive to Glucocorticoid Induction

Jennifer L. Bromberg-White and Craig Meyers^*

Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

Received 13 March 2002/ Accepted 19 June 2002

The upstream regulatory region (URR) of various types of human papillomaviruses (HPVs) has been shown to contain functional glucocorticoid response elements (GREs), including HPV type 11 (HPV11), HPV16, and HPV18. Glucocorticoids have been demonstrated to induce the transcriptional activity of the early promoters of these HPV types. Although it has been assumed that the URR of HPV31 contains at least one GRE, no functionality has been demonstrated. We attempt to show here inducibility of the URR of HPV31 by the synthetic glucocorticoid dexamethasone (dex). By sequence analysis we identified three potential GREs in the URR of HPV31. Gel shift analysis indicated that each of these three sites has the potential to be a functional GRE. However, constructs containing the full-length URR, 5' deletions of the URR, and an internal fragment of the URR containing all three putative GREs were only weakly inducible by dex. Linker scanning mutants, whereby each potential GRE was replaced individually, in double combination, or in triple combination by a unique polylinker, had no effect on dex inducibility. Replacement of each of the three HPV31 GREs with the GRE of HPV18 failed to induce a response to dex. Placement of the HPV18 GRE into the URR of HPV31 in a region similar to its location in the HPV18 URR was also unable to result in a strong dex induction of the HPV31 URR. These data suggest that the lack of dex inducibility is due to the overall context of the HPV31 URR and may be dependent on the requirements of the major early promoter for transcriptional activation. Finally, replacement of the HPV18 GRE with each of the HPV31 GREs in HPV18 only showed weak inducibility, indicating that the three GREs of HPV31 are in fact only weak inducers of dex. Overall, these data suggest that dex responsiveness, along with oncogenic potential, may provide a possible explanation for the classification of HPV31 as an intermediate-risk virus and demonstrate the complexity of transcriptional regulation of the URR of HPV.

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* Corresponding author. Mailing address: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033. Phone: (717) 531-6240. Fax: (717) 531-4600. E-mail: cmm10{at}psu.edu.

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Journal of Virology, October 2002, p. 9702-9715, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9702-9715.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

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• Bromberg-White, J. L., Sen, E., Alam, S., Bodily, J. M., Meyers, C. (2003). Induction of the Upstream Regulatory Region of Human Papillomavirus Type 31 by Dexamethasone Is Differentiation Dependent. J. Virol. 77: 10975-10983 [Abstract] [Full Text]