INVESTIGADORES
BOCCACCIO Graciela Lidia
artículos
Título:
Junin virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eIF2á phosphorylation (COVER ARTICLE)
Autor/es:
LINERO, FN;; THOMAS MG; BOCCACCIO GL; SCOLARO L
Revista:
JOURNAL OF GENERAL VIROLOGY
Editorial:
SOC GENERAL MICROBIOLOGY
Referencias:
Año: 2011 vol. 92 p. 2889 - 2899
ISSN:
0022-1317
Resumen:
Stress granules (SGs) are ephemeral cytoplasmic aggregates containing stalled translation
preinitiation complexes involved in mRNA storage and triage during the cellular stress response.
SG formation is triggered by the phosphorylation of the alpha subunit of eIF2 (eIF2a), which provokes
a dramatic blockage of protein translation. Our results demonstrate that acute infection of Vero cells
with the arenavirus Juný´n (JUNV), aetiological agent of Argentine haemorrhagic fever, does not induce
the formation of SGs. Moreover, JUNV negatively modulates SG formation in infected cells stressed
with arsenite, and this inhibition correlates with low levels of eIF2a phosphorylation. Transient
expression of JUNV nucleoprotein (N) or the glycoprotein precursor (GPC), but not of the matrix
protein (Z), inhibits SG formation in a similar manner, comparable to infectious virus. Expression of N
and GPC also impaired eIF2a phosphorylation triggered by arsenite. A moderate inhibition of SG
formation was also observed when DTT and thapsigargin were employed as stress inducers. In
contrast, no inhibition was observed when infected cells were treated with hippuristanol, a
translational inhibitor and inducer of SGs that bypasses the requirement for eIF2a phosphorylation.
Finally, we analysed SG formation in persistently JUNV-infected cells, where N and GPC are virtually
absent and truncated N products are expressed abundantly.Wefound that persistently infected cells
show a quite normal response to arsenite, with SG formation comparable to that of uninfected cells.
This suggests that the presence of GPC and/or N is crucial to control the stress response upon
JUNV infection of Vero cells.