Phosphatydilinositol-3-kinase/Akt cellular pathway in Junín virus protein

LINERO, FLORENCIA; SCOLARO, LUIS

Tucumán, Argentina

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en; 2009

SAIB

In this work we studied the participation of the phosphatidylinositol 3-kinase/Protein kinase B (PI3K/Akt) cellular pathway in the translation mechanism of Junin virus (JUNV). Since this pathway plays a central role in the regulation of the cellular cap-dependent translation and JUNV mRNAs are capped, we evaluated if this pathway activation was also necessary for an efficient translation of viral proteins. First when we analized JUNV replication in Vero cells treated with 20 µM Ly294002 (PI3K inhibitor) at different times p.i. we observed an inhibitory effect only when the inhibitor was added at early times. Then we evaluated if the uptake of JUNV was responsible for this activation using chlorpromazine, an inhibitor of JUNV entry. We did not observe Akt activation in the presence of this compound indicating that internalization of JUNV into cells was responsible of this activation. Finally, we tested the participation of eIF4E in the transaltion of JUNV proteins using rapamycin and a negative dominant 4E-BP plasmid. In both cases we did not observe an inhibitory effect on viral proteins expression and virus yield. These results suggest that, although JUNV mRNAs have a cap structure and the virus can activate the pathway implicated in the regulation of cap-dependent translation, this pathway, or at less eIF4E translation factor, is not implicated in the translation of JUNV proteins.