Junín virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eiF2α phosphorylation
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 (eIF2α), which provokes a dramatic...
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todo:paper_00221317_v92_n12_p2889_Linero2023-10-03T14:27:25Z Junín virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eiF2α phosphorylation Linero, F.N. Thomas, M.G. Boccaccio, G.L. Scolaro, L.A. arsenic trioxide dithiothreitol glycoprotein initiation factor 2alpha nucleoprotein protein precursor thapsigargin arsenous acid derivative initiation factor 2 messenger RNA animal cell Argentine hemorrhagic fever article cell granule controlled study Junin virus nonhuman priority journal protein phosphorylation Vero cell American hemorrhagic fever animal cell granule Cercopithecus drug antagonism genetic transfection genetics Junin virus metabolism methodology pathogenicity phosphorylation plasmid Arenavirus Junin virus Animals Arsenites Cercopithecus aethiops Cytoplasmic Granules Eukaryotic Initiation Factor-2 Hemorrhagic Fever, American Junin virus Phosphorylation Plasmids RNA, Messenger Transfection Vero Cells 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 (eIF2α), which provokes a dramatic blockage of protein translation. Our results demonstrate that acute infection of Vero cells with the arenavirus Juni{dotless} ́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 eIF2α 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 eIF2α 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 eIF2α 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 © 2011 SGM. Fil:Linero, F.N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Thomas, M.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Boccaccio, G.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Scolaro, L.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00221317_v92_n12_p2889_Linero |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
arsenic trioxide dithiothreitol glycoprotein initiation factor 2alpha nucleoprotein protein precursor thapsigargin arsenous acid derivative initiation factor 2 messenger RNA animal cell Argentine hemorrhagic fever article cell granule controlled study Junin virus nonhuman priority journal protein phosphorylation Vero cell American hemorrhagic fever animal cell granule Cercopithecus drug antagonism genetic transfection genetics Junin virus metabolism methodology pathogenicity phosphorylation plasmid Arenavirus Junin virus Animals Arsenites Cercopithecus aethiops Cytoplasmic Granules Eukaryotic Initiation Factor-2 Hemorrhagic Fever, American Junin virus Phosphorylation Plasmids RNA, Messenger Transfection Vero Cells |
| spellingShingle |
arsenic trioxide dithiothreitol glycoprotein initiation factor 2alpha nucleoprotein protein precursor thapsigargin arsenous acid derivative initiation factor 2 messenger RNA animal cell Argentine hemorrhagic fever article cell granule controlled study Junin virus nonhuman priority journal protein phosphorylation Vero cell American hemorrhagic fever animal cell granule Cercopithecus drug antagonism genetic transfection genetics Junin virus metabolism methodology pathogenicity phosphorylation plasmid Arenavirus Junin virus Animals Arsenites Cercopithecus aethiops Cytoplasmic Granules Eukaryotic Initiation Factor-2 Hemorrhagic Fever, American Junin virus Phosphorylation Plasmids RNA, Messenger Transfection Vero Cells Linero, F.N. Thomas, M.G. Boccaccio, G.L. Scolaro, L.A. Junín virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eiF2α phosphorylation |
| topic_facet |
arsenic trioxide dithiothreitol glycoprotein initiation factor 2alpha nucleoprotein protein precursor thapsigargin arsenous acid derivative initiation factor 2 messenger RNA animal cell Argentine hemorrhagic fever article cell granule controlled study Junin virus nonhuman priority journal protein phosphorylation Vero cell American hemorrhagic fever animal cell granule Cercopithecus drug antagonism genetic transfection genetics Junin virus metabolism methodology pathogenicity phosphorylation plasmid Arenavirus Junin virus Animals Arsenites Cercopithecus aethiops Cytoplasmic Granules Eukaryotic Initiation Factor-2 Hemorrhagic Fever, American Junin virus Phosphorylation Plasmids RNA, Messenger Transfection Vero Cells |
| description |
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 (eIF2α), which provokes a dramatic blockage of protein translation. Our results demonstrate that acute infection of Vero cells with the arenavirus Juni{dotless} ́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 eIF2α 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 eIF2α 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 eIF2α 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 © 2011 SGM. |
| format |
JOUR |
| author |
Linero, F.N. Thomas, M.G. Boccaccio, G.L. Scolaro, L.A. |
| author_facet |
Linero, F.N. Thomas, M.G. Boccaccio, G.L. Scolaro, L.A. |
| author_sort |
Linero, F.N. |
| title |
Junín virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eiF2α phosphorylation |
| title_short |
Junín virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eiF2α phosphorylation |
| title_full |
Junín virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eiF2α phosphorylation |
| title_fullStr |
Junín virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eiF2α phosphorylation |
| title_full_unstemmed |
Junín virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eiF2α phosphorylation |
| title_sort |
junín virus infection impairs stress-granule formation in vero cells treated with arsenite via inhibition of eif2α phosphorylation |
| url |
http://hdl.handle.net/20.500.12110/paper_00221317_v92_n12_p2889_Linero |
| work_keys_str_mv |
AT linerofn juninvirusinfectionimpairsstressgranuleformationinverocellstreatedwitharseniteviainhibitionofeif2aphosphorylation AT thomasmg juninvirusinfectionimpairsstressgranuleformationinverocellstreatedwitharseniteviainhibitionofeif2aphosphorylation AT boccacciogl juninvirusinfectionimpairsstressgranuleformationinverocellstreatedwitharseniteviainhibitionofeif2aphosphorylation AT scolarola juninvirusinfectionimpairsstressgranuleformationinverocellstreatedwitharseniteviainhibitionofeif2aphosphorylation |
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1782023486820057088 |