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Journal of Virology, April 2008, p. 3665-3678, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.02140-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Polypyrimidine Tract Binding Protein Induces Human Papillomavirus Type 16 Late Gene Expression by Interfering with Splicing Inhibitory Elements at the Major Late 5' Splice Site, SD3632{triangledown}

Monika Somberg,1 Xiaomin Zhao,1 Monika Fröhlich,2 Magnus Evander,2 and Stefan Schwartz1*

Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, Uppsala,1 Department of Virology, Umeå University, Umeå, Sweden2

Received 28 September 2007/ Accepted 14 January 2008

We have initiated a screen for cellular factors that can induce human papillomavirus type 16 (HPV-16) late gene expression in human cancer cells. We report that the overexpression of polypyrimidine tract binding protein (PTB), also known as heterologous nuclear ribonucleoprotein I (hnRNP I), induces HPV-16 late gene expression in cells transfected with subgenomic HPV-16 plasmids or with full-length HPV-16 genomes and in persistently HPV-16-infected cells. In contrast, other hnRNPs such as hnRNP B1/A2, hnRNP F, and hnRNP Q do not induce HPV-16 late gene expression. PTB activates SD3632, the only 5' splice site on the HPV-16 genome that is used exclusively by late mRNAs. PTB interferes with splicing inhibitory sequences located immediately upstream and downstream of SD3632, thereby activating late gene expression. One AU-rich PTB-responsive element was mapped to a 198-nucleotide sequence located downstream of SD3632. The deletion of this element induced HPV-16 late gene expression in the absence of PTB. Our results suggest that the overexpression of PTB interferes with cellular factors that interact with the inhibitory sequences. One may speculate that an increase in PTB levels or a reduction in the concentration of a PTB antagonist is required for the activation of HPV-16 late gene expression during the viral life cycle.

* Corresponding author. Mailing address: Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Centre, Husargatan 3, Box 582, 751 23 Uppsala, Sweden. Phone: 4618 4714239. Fax: 4618 4714673. E-mail: Stefan.Schwartz{at}imbim.uu.se

{triangledown} Published ahead of print on 23 January 2008.

Journal of Virology, April 2008, p. 3665-3678, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.02140-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mole, S., Milligan, S. G., Graham, S. V. (2009). Human Papillomavirus Type 16 E2 Protein Transcriptionally Activates the Promoter of a Key Cellular Splicing Factor, SF2/ASF. J. Virol. 83: 357-367 [Abstract] [Full Text]  


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