A crude membrane-bound replication complex isolated from encephalomyocarditis virus-infected ceils is able to initiate the synthesis of viral RNA. Both the formation of the primer, VPg-pU, and its utilization for the initiation of RNA chains take place in this system. A significant amount of the synthesized VPg-pU is found in the free fonn. The predominant product of the de novo initiation is represented by short phenol-soluble VPg oligonucleotide species, and only a smail percentage of the latter appear to be elongated into longer RNA chains.
Picornaviruses are small animal viruses with positive-strand genomic RNA, which is translated using cap-independent internal translation initiation. The key role in this is played by cis elements of the 5'-untranslated region (5'-UTR) and, in particular, by the internal ribosome entry site (IRES). The function of translational cis elements requires both canonical translation initiation factors (eIFs) and additional IRES transacting factors (ITAFs). All known ITAFs are cell RNA-binding proteins which play a variety of functions in noninfected cells. Specific features of translational cis elements substantially affect the phenotype and, in particular, tissue tropism and pathogenic properties of picornaviruses. It is clear that, in some cases, the molecular mechanism involved is a change in interactions between viral cis elements and ITAFs. The properties and tissue distribution of ITAFs may determine the biological properties of other viruses that also use the IRES-dependent translation initiation. Since this mechanism is also involved in translation of several cell mRNAs, ITAF may contribute to the regulation of the most important aspects of the living activity in noninfected cells.
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