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Inhibition of translation by poliovirus: inactivation of a specific initiation factor
Abstract:
Translation of vesicular stomatitis virus (VSV) mRNA, like host mRNA translation, is inhibited in cells infected with poliovirus. To study the mechanism of poliovirus-induced inhibition of protein synthesis, we prepared extracts from poliovirus-infected and uninfected HeLa cells. Poliovirus mRNA was translated in lysates from both infected and uninfected cells, while VSV mRNA was translated only in the lysate from uninfected cells. Addition of purified translation initiation factors to the extract from infected cells showed that one factor, eIF-4B, could restore VSV mRNA translation in the infected lysate, but did not increase poliovirus mRNA translation. Further experiments involving translation of VSV mRNA in mixed extracts from poliovirus-infected and uninfected cells showed (i) that there was not an excess of an inhibitor of VSV mRNA translation in the infected lysate, but (ii) that an acitivity that caused a slow inactivation of eIF-4B was present in the infected lysate. Inactivation of eIF-4B appears to be the mechanism by which poliovirus infection causes a selective inhibition of translation.
Insights
Poliovirus infection selectively inhibits protein synthesis by inactivating the translation factor eIF-4B. This mechanism explains how poliovirus disrupts host and viral mRNA translation, impacting cellular processes.
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- Poliovirus infection inhibits the translation of both host and viral mRNA, including vesicular stomatitis virus (VSV) mRNA.
- Understanding the mechanism of this selective inhibition is crucial for comprehending viral pathogenesis.
Purpose of the Study:
- To elucidate the molecular mechanism by which poliovirus inhibits protein synthesis.
- To identify the specific factors involved in the selective translation shutoff during poliovirus infection.
Main Methods:
- Preparation of cell extracts from poliovirus-infected and uninfected HeLa cells.
- In vitro translation assays using poliovirus and VSV mRNA in different cell lysates.
- Addition of purified translation initiation factors, specifically eIF-4B, to assess restoration of translation.
Main Results:
- VSV mRNA translation was observed only in lysates from uninfected cells, while poliovirus mRNA translated in both.
- Addition of eIF-4B restored VSV mRNA translation in infected lysates but did not enhance poliovirus mRNA translation.
- An activity causing slow inactivation of eIF-4B was identified in infected cell lysates, with no evidence of a trans-acting inhibitor.
Conclusions:
- Poliovirus selectively inhibits protein synthesis by causing a slow inactivation of the translation initiation factor eIF-4B.
- This inactivation mechanism explains the differential translation efficiency observed between poliovirus and VSV mRNA during infection.