Translation driven by picornavirus IRES is hampered from Sindbis virus replicons: rescue by poliovirus 2A protease

Journal of Molecular Biology
Miguel Angel SanzL Carrasco

Abstract

Alphavirus replicons are very useful for analyzing different aspects of viral molecular biology. They are also useful tools in the development of new vaccines and highly efficient expression of heterologous genes. We have investigated the translatability of Sindbis virus (SV) subgenomic mRNA bearing different 5'-untranslated regions, including several viral internal ribosome entry sites (IRESs) from picornaviruses, hepatitis C virus, and cricket paralysis virus. Our findings indicate that all these IRES-containing mRNAs are initially translated in culture cells transfected with the corresponding SV replicon but their translation is inhibited in the late phase of SV replication. Notably, co-expression of different poliovirus (PV) non-structural genes reveals that the protease 2A (2A(pro)) is able to increase translation of subgenomic mRNAs containing the PV or encephalomyocarditis virus IRESs but not of those of hepatitis C virus or cricket paralysis virus. A PV 2A(pro) variant deficient in eukaryotic initiation factor (eIF) 4GI cleavage or PV protease 3C, neither of which cleaves eIF4GI, does not increase picornavirus IRES-driven translation, whereas L protease from foot-and-mouth disease virus also rescues translation. These f...Continue Reading

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Citations

Jul 1, 2011·Journal of Virology·Shin-Ru ShihMei-Ling Li
Jul 23, 2011·PloS One·Ewelina WelnowskaLuis Carrasco
Oct 18, 2011·PloS One·Natalia RedondoLuis Carrasco
Feb 28, 2017·Scientific Reports·Miguel Angel SanzLuis Carrasco
Feb 9, 2018·Viruses·Luis CarrascoEsther González-Almela
Aug 9, 2017·Frontiers in Microbiology·Xiaoyao YangXiaoyue Chen
Jan 9, 2020·Journal of Biomedical Science·Ming-Chih LaiRobert Y L Wang

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