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Molecular and Cellular Biology, October 2005, p. 8643-8655, Vol. 25, No. 19
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.19.8643-8655.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Gene Codon Composition Determines Differentiation-Dependent Expression of a Viral Capsid Gene in Keratinocytes In Vitro and In Vivo

Kong-Nan Zhao,^* WenYi Gu, Ning Xia Fang, Nicholas A. Saunders, and Ian H. Frazer^*

Centre for Immunology and Cancer Research, The University of Queensland, Research Extension, Building 1, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland 4102, Australia

Received 18 March 2005/ Returned for modification 28 April 2005/ Accepted 11 July 2005

By establishing mouse primary keratinocytes (KCs) in culture, we were able, for the first time, to express papillomavirus major capsid (L1) proteins by transient transfection of authentic or codon-modified L1 gene expression plasmids. We demonstrate in vitro and in vivo that gene codon composition is in part responsible for differentiation-dependent expression of L1 protein in KCs. L1 mRNA was present in similar amounts in differentiated and undifferentiated KCs transfected with authentic or codon-modified L1 genes and had a similar half-life, demonstrating that L1 protein production is posttranscriptionally regulated. We demonstrate further that KCs substantially change their tRNA profiles upon differentiation. Aminoacyl-tRNAs from differentiated KCs but not undifferentiated KCs enhanced the translation of authentic L1 mRNA, suggesting that differentiation-associated change to tRNA profiles enhances L1 expression in differentiated KCs. Thus, our data reveal a novel mechanism for regulation of gene expression utilized by a virus to direct viral capsid protein expression to the site of virion assembly in mature KCs. Analysis of two structural proteins of KCs, involucrin and keratin 14, suggests that translation of their mRNAs is also regulated, in association with KC differentiation in vitro, by a similar mechanism.

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* Corresponding author. Mailing address: Centre for Immunology and Cancer Research, The University of Queensland, Research Extension, Building 1, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland 4102, Australia. Phone: 07 3240 5282. Fax: 07 3240 5946. E-mail for Kong-Nan Zhao: knzhao{at}cicr.uq.edu.au. E-mail for Ian H. Frazar: ifrazar{at}cicr.uq.edu.au.

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Molecular and Cellular Biology, October 2005, p. 8643-8655, Vol. 25, No. 19
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.19.8643-8655.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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