Inhibition of the PI3K/Akt pathway by Ly294002 does not prevent establishment of persistent Junín virus infection in Vero cells
In previous work, we demonstrated that the arenavirus Junín virus (JUNV) is able to activate Akt by means of the phosphatidylinositol-3-kinase (PI3K) survival pathway during virus entry. This work extends our study, emphasizing the relevance of this pathway in the establishment and maintenance of pe...
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todo:paper_03048608_v160_n2_p469_Linero2023-10-03T15:21:01Z Inhibition of the PI3K/Akt pathway by Ly294002 does not prevent establishment of persistent Junín virus infection in Vero cells Linero, F.N. Fernández Bell-Fano, P.M. Cuervo, E. Castilla, V. Scolaro, L.A. Junín virus LY294002 Persistence PI3K/AKT 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one chromone derivative enzyme inhibitor morpholine derivative phosphatidylinositol 3 kinase protein kinase B virus protein animal antagonists and inhibitors apoptosis biosynthesis cell line Chlorocebus aethiops drug effects growth, development and aging Hemorrhagic Fever, American Junin virus physiology Vero cell line virology virus entry virus replication Animals Apoptosis Cell Line Cercopithecus aethiops Chromones Enzyme Inhibitors Hemorrhagic Fever, American Junin virus Morpholines Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-akt Vero Cells Viral Proteins Virus Internalization Virus Replication In previous work, we demonstrated that the arenavirus Junín virus (JUNV) is able to activate Akt by means of the phosphatidylinositol-3-kinase (PI3K) survival pathway during virus entry. This work extends our study, emphasizing the relevance of this pathway in the establishment and maintenance of persistent infection in vitro. During the course of infection, JUNV-infected Vero cells showed a typical cytopathic effect that may be ascribed to apoptotic cell death. Treatment of infected cultures with Ly294002, an inhibitor of the PI3K/Akt pathway, produced an apoptotic response similar to that observed for uninfected cells treated with the drug. This result suggests that virus-induced activation of the PI3K/Akt pathway does not deliver a strong enough anti-apoptotic signal to explain the low proportion of apoptotic cells observed during infection. Also, inhibition of the PI3K/Akt pathway during the acute stage of infection did not prevent the establishment of persistence. Furthermore, treatment of persistently JUNV-infected cells with Ly294002 did not alter viral protein expression. These findings indicate that despite the positive modulation of the PI3/Akt pathway during Junín virus entry, this would not play a critical role in the establishment and maintenance of JUNV persistence in Vero cells. © 2014, Springer-Verlag Wien. Fil:Linero, F.N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fernández Bell-Fano, P.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Castilla, V. 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_03048608_v160_n2_p469_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 |
Junín virus LY294002 Persistence PI3K/AKT 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one chromone derivative enzyme inhibitor morpholine derivative phosphatidylinositol 3 kinase protein kinase B virus protein animal antagonists and inhibitors apoptosis biosynthesis cell line Chlorocebus aethiops drug effects growth, development and aging Hemorrhagic Fever, American Junin virus physiology Vero cell line virology virus entry virus replication Animals Apoptosis Cell Line Cercopithecus aethiops Chromones Enzyme Inhibitors Hemorrhagic Fever, American Junin virus Morpholines Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-akt Vero Cells Viral Proteins Virus Internalization Virus Replication |
spellingShingle |
Junín virus LY294002 Persistence PI3K/AKT 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one chromone derivative enzyme inhibitor morpholine derivative phosphatidylinositol 3 kinase protein kinase B virus protein animal antagonists and inhibitors apoptosis biosynthesis cell line Chlorocebus aethiops drug effects growth, development and aging Hemorrhagic Fever, American Junin virus physiology Vero cell line virology virus entry virus replication Animals Apoptosis Cell Line Cercopithecus aethiops Chromones Enzyme Inhibitors Hemorrhagic Fever, American Junin virus Morpholines Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-akt Vero Cells Viral Proteins Virus Internalization Virus Replication Linero, F.N. Fernández Bell-Fano, P.M. Cuervo, E. Castilla, V. Scolaro, L.A. Inhibition of the PI3K/Akt pathway by Ly294002 does not prevent establishment of persistent Junín virus infection in Vero cells |
topic_facet |
Junín virus LY294002 Persistence PI3K/AKT 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one chromone derivative enzyme inhibitor morpholine derivative phosphatidylinositol 3 kinase protein kinase B virus protein animal antagonists and inhibitors apoptosis biosynthesis cell line Chlorocebus aethiops drug effects growth, development and aging Hemorrhagic Fever, American Junin virus physiology Vero cell line virology virus entry virus replication Animals Apoptosis Cell Line Cercopithecus aethiops Chromones Enzyme Inhibitors Hemorrhagic Fever, American Junin virus Morpholines Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-akt Vero Cells Viral Proteins Virus Internalization Virus Replication |
description |
In previous work, we demonstrated that the arenavirus Junín virus (JUNV) is able to activate Akt by means of the phosphatidylinositol-3-kinase (PI3K) survival pathway during virus entry. This work extends our study, emphasizing the relevance of this pathway in the establishment and maintenance of persistent infection in vitro. During the course of infection, JUNV-infected Vero cells showed a typical cytopathic effect that may be ascribed to apoptotic cell death. Treatment of infected cultures with Ly294002, an inhibitor of the PI3K/Akt pathway, produced an apoptotic response similar to that observed for uninfected cells treated with the drug. This result suggests that virus-induced activation of the PI3K/Akt pathway does not deliver a strong enough anti-apoptotic signal to explain the low proportion of apoptotic cells observed during infection. Also, inhibition of the PI3K/Akt pathway during the acute stage of infection did not prevent the establishment of persistence. Furthermore, treatment of persistently JUNV-infected cells with Ly294002 did not alter viral protein expression. These findings indicate that despite the positive modulation of the PI3/Akt pathway during Junín virus entry, this would not play a critical role in the establishment and maintenance of JUNV persistence in Vero cells. © 2014, Springer-Verlag Wien. |
format |
JOUR |
author |
Linero, F.N. Fernández Bell-Fano, P.M. Cuervo, E. Castilla, V. Scolaro, L.A. |
author_facet |
Linero, F.N. Fernández Bell-Fano, P.M. Cuervo, E. Castilla, V. Scolaro, L.A. |
author_sort |
Linero, F.N. |
title |
Inhibition of the PI3K/Akt pathway by Ly294002 does not prevent establishment of persistent Junín virus infection in Vero cells |
title_short |
Inhibition of the PI3K/Akt pathway by Ly294002 does not prevent establishment of persistent Junín virus infection in Vero cells |
title_full |
Inhibition of the PI3K/Akt pathway by Ly294002 does not prevent establishment of persistent Junín virus infection in Vero cells |
title_fullStr |
Inhibition of the PI3K/Akt pathway by Ly294002 does not prevent establishment of persistent Junín virus infection in Vero cells |
title_full_unstemmed |
Inhibition of the PI3K/Akt pathway by Ly294002 does not prevent establishment of persistent Junín virus infection in Vero cells |
title_sort |
inhibition of the pi3k/akt pathway by ly294002 does not prevent establishment of persistent junín virus infection in vero cells |
url |
http://hdl.handle.net/20.500.12110/paper_03048608_v160_n2_p469_Linero |
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1807315015943847936 |