Modulation of stress response in persistently infected Vero cells with the arenavirus Junin

LINERO, FLORENCIA; FERNÁNDEZ BELL FANO, PABLO; CUERVO, EUGENIA; CASTILLA, VIVIANA; SCOLARO, LUIS

Sapporo

Congreso; XV International Congress of Virology; 2011

IUMS

Viruses belonging to the family Arenaviridae are able to cause persistent infection in several species of rodents that act as reservoirs, ensuring their evolution and perpetuation in nature. Also arenaviruses replicate in vitro in a wide variety of mammalian cell cultures and the stage of viral persistence can be achieved in most of the cell lines suitable for virus growth. The arenavirus Junin (JUNV), causative of a life-threatening hemorrhagic human disease, is able to persist in the cricetid Calomys musculinus and in different cell cultures as well. The aim of this work was to analyze the stress response of Vero cells persistently infected with JUNV (named V3). To this goal we analyzed in first place the susceptibility of this culture to form stress granules (SGs) in response to different stress inductors. Results showed that V3 cells were able to induce SGs, showing an augment in the number of SGs in comparison to uninfected cells. Since SGs formation is a response to avoid apoptotic cell death, we evaluated the resistance of V3 cells to apoptotic inductors such as PI3K/Akt inhibitors, caffeine and Ly294002, or exposure to ultraviolet radiation. V3 cells proved to be more resistant to these treatments comparatively to uninfected cells. Finally we analyzed the expression of the ribonucleoproteins hnRNP A1, a nuclear component that shuttles between nucleus and cytoplasm regulating the translation of pro-apoptotic factors. We found a very slightly expression of hnRNPA1 in persistent cultures, and a significant re-localization to the nucleus when exogenous over-expression of hnRNPA1 was performed. These results showed that the ability of JUNV persistently infected cells to induce an increased SGs formation together with a down regulation of the expression of hnRNPA1, may contribute to an anti-apoptotic state of this culture.