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J Virol, February 1998, p. 1504-1515, Vol. 72, No. 2
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

mRNA Instability Elements in the Human Papillomavirus Type 16 L2 Coding Region

Marcus Sokolowski, Wei Tan, Marianne Jellne, and Stefan Schwartz^*

Microbiology and Tumorbiology Center, Karolinska Institute, 171 77 Stockholm, Sweden

Received 14 August 1997/Accepted 3 November 1997

Human papillomavirus capsid proteins L1 and L2 are detected only in terminally differentiated cells, indicating that expression of the L1 and L2 genes is blocked in dividing cells. The results presented here establish that the human papillomavirus type 16 L2 coding region contains cis-acting inhibitory sequences. When placed downstream of a reporter gene, the human papillomavirus type 16 L2 sequence reduced both mRNA and protein levels in an orientation-dependent manner. Deletion analysis revealed that the L2 sequence contains two cis-acting inhibitory RNA regions. We identified an inhibitory region in the 5'-most 845 nucleotides of L2 that acted by reducing cytoplasmic mRNA stability and a second, weaker inhibitory region in the 3' end of L2. In contrast, human papillomavirus type 1 L1 and L2 genes did not encode strong inhibitory sequences. This result is consistent with observations of high virus production in human papillomavirus type 1-infected tissue, whereas only low levels of human papillomavirus type 16 virions are detectable in infected epithelium. The presence of inhibitory sequences in the L1 and L2 mRNAs may aid the virus in avoiding the host immunosurveillance and in establishing persistent infections.

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^* Corresponding author. Present address: Department of Medical Immunology and Microbiology, Biomedical Center, Uppsala University, P.O. Box 582, 751 23 Uppsala, Sweden. Phone: 4618 471 4928. Fax: 4618 509 876. E-mail: Stefan.Schwartz{at}imim.uu.se.

Present address: Department of Medical Immunology and Microbiology, BMC, Uppsala University, 751 23 Uppsala, Sweden.

Present address: The John P. Robarts Research Institute, London, Ontario N6A 5K8, Canada.

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