Targeting internal ribosome entry site (IRES)-mediated translation to block hepatitis C and other RNA viruses

Dasgupta, Asim ; Das, Saumitra ; Izumi, Raquel ; Venkatesan, Arun ; Barat, Bhaswati (2004) Targeting internal ribosome entry site (IRES)-mediated translation to block hepatitis C and other RNA viruses FEMS Microbiology Letters, 234 (2). pp. 189-199. ISSN 0378-1097

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A number of RNA-containing viruses such as hepatitis C (HCV) and poliovirus (PV) that infect human beings and cause serious diseases use a common mechanism for synthesis of viral proteins, termed internal ribosome entry site (IRES)-mediated translation. This mode of translation initiation involves entry of 40S ribosome internally to the 5' untranslated region (UTR) of viral RNA. Cap-dependent translation of cellular mRNAs, on the other hand, requires recognition of mRNA 5' cap by the translation machinery. In this review, we discuss two inhibitors that specifically inhibit viral IRES-mediated translation without interfering with cellular cap-dependent translation. We present evidence, which suggest that one of these inhibitors, a small RNA (called IRNA) originally isolated from the yeast Saccharomyces cerevisiae, inhibits viral IRES-mediated translation by sequestering both noncanonical transacting factors and canonical initiation factors required for IRES-mediated translation. The other inhibitor, a small peptide from the lupus autoantigen La (called LAP), appears to block binding of cellular transacting factors to viral IRES elements. These results suggest that it might be possible to target viral IRES-mediated translation for future development of therapeutic agents effective against a number of RNA viruses including HCV that exclusively use cap-independent translation for synthesis of viral proteins.

Item Type:Article
Source:Copyright of this article belongs to Federation of European Microbiological Societies.
Keywords:IRES-mediated Translation; RNA Viruses; Hepatitis C Virus; Antivirals
ID Code:8637
Deposited On:28 Oct 2010 11:13
Last Modified:16 May 2016 18:35

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