Every year hundreds of thousands of children are infected with enterovirus 71 (EV71). Infection with EV71 can lead to serious complications such as polio-like paralysis, encephalitis, meningitis or even death. Currently, there is no treatment or vaccine against EV71. EV71 belongs to the picornavirus family, whose members contain positive-stranded RNA genomes that are translated by an unusual mechanism of internal ribosome entry. The differences between the model of translational initiation of most cellular and viral mRNAs will be exploited to identify small peptides that can selectively inhibit the translation of the EV71 mRNA. Specifically, retroviruses expressing conformationally constrained peptide libraries will be used to infect cells expressing the EV71 5' non-coding region linked to an enhanced green fluorescent protein (EGFP) reporter gene and a cellular c-myc 5' non- coding region linked to an enhanced yellow fluorescence protein (EYFP). Infected cells which fail to express EGFP but still express EYFP will be isolated by cell sorting, and the gene encoding the putative inhibitor will be isolated . Studying the targets of the inhibitory peptides and characterizing the molecular interactions that they are disrupting will reveal more about how viruses function to recruit host cell molecules for their translation. Selection and characterization of intracellularly stable peptides that can inhibit the amplification of a viral RNA genome should level to novel ways in the search for antiviral therapeutics.
| Thompson, S R; Sarnow, P (2000) Regulation of host cell translation by viruses and effects on cell function. Curr Opin Microbiol 3:366-70 |
