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Journal of Virology, June 1999, p. 4972-4982, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Papillomavirus Capsid Protein Expression Level Depends on the Match between Codon Usage and tRNA Availability

Jian Zhou,dagger Wen Jun Liu, Shi Wen Peng, Xiao Yi Sun, and Ian Frazer*

Centre for Immunology & Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia

Received 25 November 1998/Accepted 11 February 1999

Translation of mRNA encoding the L1 and L2 capsid proteins of papillomavirus (PV) is restricted in vivo to differentiated epithelial cells, although transcription of the L1 and L2 late genes occurs more widely. The codon composition of PV late genes is quite different from that of most mammalian genes. To test the possibility that PV late gene codon composition determines the efficiency of PV late gene expression in some cell types, synthetic bovine papillomavirus type 1 (BPV1) late genes were constructed with codon composition modified to resemble the typical mammalian gene. Expression of these genes from a strong promoter in Cos-1 cells was compared with expression of wild-type BPV1 late genes from the same promoter. Both unmodified and modified PV late genes were transcribed in Cos-1 cells, but only the codon-modified genes were translated. In vitro translation of wild-type but not synthetic BPV1 L1 mRNA was markedly enhanced by addition of aminoacyl-tRNAs. Codon composition thus limits BPV1 late gene translation in Cos-1 cells, and this limitation can be overcome by modification of the codon composition of the genes or by provision of excess tRNA. Replacement of codons in the green fluorescent protein (gfp) gene with those frequently used in PV late genes did not alter gfp transcription in Cos-1 cells but almost abolished translation, supporting the hypothesis that the observed differences in efficiency of translation of modified and unmodified PV capsid genes were related to codon usage rather than mRNA structure. As tRNA populations vary within and between tissues in the same eukaryotic organism, we speculate that matching of tRNA availability to codon usage may be one determinant of the restriction of expression of PV late genes to differentiated epithelium.

* Corresponding author. Mailing address: Centre for Immunology & Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane QLD 4102, Australia. Phone: 61-7-3240 5315. Fax: 61-7-3240 2048. E-mail: ifrazer{at}medicine.pa.uq.edu.au.

dagger Jian Zhou passed away in Hangzhou, China, on 10 March 1999 after a brief illness. He is greatly missed.

Journal of Virology, June 1999, p. 4972-4982, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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