C. Shaw-jackson et T. Michiels, Absence of internal ribosome entry site-mediated tissue specificity in thetranslation of a bicistronic transgene, J VIROLOGY, 73(4), 1999, pp. 2729-2738
The 5' noncoding regions of the genomes of picornaviruses form a complex st
ructure that directs cap-independent initiation of translation. This struct
ure has been termed the internal ribosome entry site (IRES), The efficiency
of translation initiation was shown, ire vitro, to be influenced by the bi
nding of cellular factors to the IRES, Hence, we hypothesized that the IRES
might control picornavirus tropism. In order to test this possibility, we
made a bicistronic construct ire which translation of the luciferase gene i
s controlled by the IRES of Theiler's murine encephalomyelitis virus. In vi
tro, we observed that the IRES functions in various cell types and in macro
phages, irrespective of their activation state. In vivo, we observed that t
he IRES is functional in different tissues of transgenic mice. Thus, it see
ms that the IRES is not an essential determinant of Theiler's virus tropism
, On the other hand, the age of the mouse could be critical for IRES functi
on. Indeed, the IRES was found to be more efficient in young mice. Picornav
irus IRESs are becoming popular tools in transgenesis technology, since the
y allow the expression of two genes from the same transcription unit. Our r
esults show that the Theiler's virus IRES is functional in cells of differe
nt origins and that it is thus a broad-spectrum tool. The possible age depe
ndency of the IRES function, however, could be a drawback for gene expressi
on in adult mice.