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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,
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.

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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