TRANSLATIONAL STRATEGY OF NEW WORLD ARENAVIRUSES: ROLE OF THE VIRAL NUCLEOPROTEIN

LINERO, FLORENCIA; WELNOWSKA, EWELINA; CARRASCO, LUIS; SCOLARO, LUIS

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2012

SAIB

Translation of viral proteins is a key factor for viruses, which are obligate intracellular parasites and entirely dependent on the cellular translation machinery to synthesize their proteins. The aim of this work was to analyze the initial steps of protein translation during Junin (JUNV), Tacaribe (TACV) and Pichinde (PICV) virus infection. Results showed that silencing of eIF4E by a siRNA had not effect in viral protein synthesis of JUNV, TACV and PICV, respectively, suggesting an eIF4E independent translation mode. Involvement of eIF4GI, was evaluated using an specific siRNAs against this factor and by the expression of the poliovirus 2A protease that cleaves this factor. Both strategies showed a significant reduction in JUNV protein synthesis. Similar results were obtained for eIF4A, in which a significant reduction in JUNV virus replication was observed by treatment with the inhibitor hippuristanol. On the other hand, microscopy studies showed colocalization of JUNV nucleoprotein (N) with eIF4GI strongly suggesting that this viral protein would be part of the translation complex of viral mRNAs.Additionally, the presence of JUNV-N in eIF4GI and eIF4A, but not in eIF4E immune-precipitated complexes was observed. Finally JUNV-N was able to bind to a 7- methyl cap column, strongly suggesting that N could be a capbinding factor that replaces eIF4E.