Independencia de los factores de la iniciación de la traducción de los mRNAs virales

Resumo

Cytolytic viruses abrogate host protein synthesis to maximize the translation of their own mrnas. In this thesis doctoral, we analyzed the translation initiation factor requirements for translation of vesicular stomatitis virus (vsv), vaccinia virus (vv), encephalomyocarditis virus (emcv), foot-and-mouth disease virus (fmdv), influenza virus (flu) and sindbis virus (sv) mrnas in cells using different strategies. The first one is based on depletion of eifs by sirnas: Silencing of eif4gi and eif4gii only slightly affects vsv infection, whereas it has a much greater effect in cellular, flu and vv protein synthesis, showing a virus-dependent behavior regarding eif4g involvement in initiation of translation. Another strategy used was to proteolyze eif4g expressing poliovirus 2a protease (pv 2apro) in cultured cells and to analyze the translational effects of this functional impairment. Eif4g cleavage by pv 2apro strongly inhibits translation of flu and vv mrnas, whereas protein synthesis directed by vsv mrnas is not abrogated in agreement with silencing experiments. Taken together, these results suggest two opposite translation mechanisms for three distinct animal viruses (two negative stranded rna, flu and vsv, and one double stranded dna, vv, viruses) regarding to the canonical cap-dependent translation. Depletion of eif2¿ induces a slight delay in the kinetics of emcv protein synthesis, whereas at late times post infection the levels of viral translation are similar in control and eif2¿-depleted hela cells. These data suggest that emcv rna is translated by an eif2¿- independent mechanism in infected cells.