The RNA genomes of several positive-strand RNA-viruses
can be directly used for translation after infection of a cell.
These viruses include the picornaviruses like Poliovirus, Rhinoviruses,
Hepatitis A Virus and the animal pathogen Foot-and-Mouth Disease
Virus as well as Hepatitis C Virus (HCV). For the preferential translation
of their own viral proteins, these viruses bypass the normal route
of cap-dependent translation in the eukaryotic cell by a special
mechanism. The initiation of translation of viral proteins is directed
by a cis-acting region of the viral RNA, the internal ribosome entry
We investigate the interaction of these viral IRES
elements with the cellular translation apparatus. The IRES elements
of the picornaviruses recruit almost all of the standard eukaryotic
translation initiation factors (eIFs) except the Cap-binding protein
eIF4E. Moreover, the IRES activity is modulated by other cellular
RNA-binding proteins which are not involved in translation of normal
cellular mRNAs, like the polypyrimidine tract-binding protein (PTB),
the protein encoded upstream of N-ras (Unr) or the heterogeneous
nuclear ribonucleoprotein L (hnRNP L). In contrast, the IRES of
HCV can bind to the ribosome independently of initiation factors.
Although located at the other end of the genomic
RNA, also the 3´-untranslated region (3´-UTR) of HCV
is involved in translation regulation. This process is similar to
the enhancement of translation of normal cellular mRNAs, which are
bound at the Cap-nucleotide at their 5´-end by the initiation
factor eIF4F and at their poly(A)-tail at the 3´-end by the
Poly(A)-binding protein PABP. The protein-protein interaction of
PABP with eIF4F then leads to a circularization of the mRNA which
then results in a more efficient (re-) utilization of the ribosomes.
Although there is no Cap-nucleotide and no poly(A)-tail on the HCV
RNA genome, a similar protein-mediated interaction of the terminal
structures of the RNA is assumed to take place also in the process
of HCV translation.