Infection with Usutu virus induces an autophagic response in mammalian cells
Usutu virus (USUV) is an African mosquito-borne flavivirus closely related to West Nile virus and Japanese encephalitis virus, which host range includes mainly mosquitoes and birds, although infections in humans have been also documented, thus warning about USUV as a potential health threat. Circulation of USUV in Africa was documented more than 50 years ago, but it was not until the last decade that it emerged in Europe causing episodes of avian mortality and some human severe cases. Since autophagy is a cellular pathway that can play important roles on different aspects of viral infections and pathogenesis, the possible implication of this pathway in USUV infection has been examined using Vero cells and two viral strains of different origin. USUV infection induced the unfolded protein response, revealed by the splicing of Xbp-1 mRNA. Infection with USUV also stimulated the autophagic process, which was demonstrated by an increase in the cytoplasmic aggregation of microtubule-associated protein 1 light chain 3 (LC3), a marker of autophagosome formation. In addition to this, an increase in the lipidated form of LC3, that is associated with autophagosome formation, was noticed following infection. Pharmacological modulation of the autophagic pathway with the inductor of autophagy rapamycin resulted in an increase in virus yield. On the other hand, treatment with 3-methyladenine or wortmannin, two distinct inhibitors of phosphatidylinositol 3-kinases involved in autophagy, resulted in a decrease in virus yield. These results indicate that USUV virus infection upregulates the cellular autophagic pathway and that drugs that target this pathway can modulate the infection of this virus, thus identifying a potential druggable pathway in USUV-infection. © 2013 Blázquez et al.
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2013
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dig-inia-es-10261-2917012023-02-20T07:21:13Z Infection with Usutu virus induces an autophagic response in mammalian cells Blázquez Martín, Ana Belén Escribano Romero, Estela Merino-Ramos, T. Saiz Calahorra, Juan Carlos Martín-Acebes, M. A. Usutu virus (USUV) is an African mosquito-borne flavivirus closely related to West Nile virus and Japanese encephalitis virus, which host range includes mainly mosquitoes and birds, although infections in humans have been also documented, thus warning about USUV as a potential health threat. Circulation of USUV in Africa was documented more than 50 years ago, but it was not until the last decade that it emerged in Europe causing episodes of avian mortality and some human severe cases. Since autophagy is a cellular pathway that can play important roles on different aspects of viral infections and pathogenesis, the possible implication of this pathway in USUV infection has been examined using Vero cells and two viral strains of different origin. USUV infection induced the unfolded protein response, revealed by the splicing of Xbp-1 mRNA. Infection with USUV also stimulated the autophagic process, which was demonstrated by an increase in the cytoplasmic aggregation of microtubule-associated protein 1 light chain 3 (LC3), a marker of autophagosome formation. In addition to this, an increase in the lipidated form of LC3, that is associated with autophagosome formation, was noticed following infection. Pharmacological modulation of the autophagic pathway with the inductor of autophagy rapamycin resulted in an increase in virus yield. On the other hand, treatment with 3-methyladenine or wortmannin, two distinct inhibitors of phosphatidylinositol 3-kinases involved in autophagy, resulted in a decrease in virus yield. These results indicate that USUV virus infection upregulates the cellular autophagic pathway and that drugs that target this pathway can modulate the infection of this virus, thus identifying a potential druggable pathway in USUV-infection. © 2013 Blázquez et al. 2023-02-20T07:21:13Z 2023-02-20T07:21:13Z 2013 artículo PLoS Neglected Tropical Diseases 7(10): e2509 (2013) http://hdl.handle.net/20.500.12792/3940 http://hdl.handle.net/10261/291701 10.1371/journal.pntd.0002509 1935-2735 en open Public Library of Science |
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Usutu virus (USUV) is an African mosquito-borne flavivirus closely related to West Nile virus and Japanese encephalitis virus, which host range includes mainly mosquitoes and birds, although infections in humans have been also documented, thus warning about USUV as a potential health threat. Circulation of USUV in Africa was documented more than 50 years ago, but it was not until the last decade that it emerged in Europe causing episodes of avian mortality and some human severe cases. Since autophagy is a cellular pathway that can play important roles on different aspects of viral infections and pathogenesis, the possible implication of this pathway in USUV infection has been examined using Vero cells and two viral strains of different origin. USUV infection induced the unfolded protein response, revealed by the splicing of Xbp-1 mRNA. Infection with USUV also stimulated the autophagic process, which was demonstrated by an increase in the cytoplasmic aggregation of microtubule-associated protein 1 light chain 3 (LC3), a marker of autophagosome formation. In addition to this, an increase in the lipidated form of LC3, that is associated with autophagosome formation, was noticed following infection. Pharmacological modulation of the autophagic pathway with the inductor of autophagy rapamycin resulted in an increase in virus yield. On the other hand, treatment with 3-methyladenine or wortmannin, two distinct inhibitors of phosphatidylinositol 3-kinases involved in autophagy, resulted in a decrease in virus yield. These results indicate that USUV virus infection upregulates the cellular autophagic pathway and that drugs that target this pathway can modulate the infection of this virus, thus identifying a potential druggable pathway in USUV-infection. © 2013 Blázquez et al. |
format |
artículo |
author |
Blázquez Martín, Ana Belén Escribano Romero, Estela Merino-Ramos, T. Saiz Calahorra, Juan Carlos Martín-Acebes, M. A. |
spellingShingle |
Blázquez Martín, Ana Belén Escribano Romero, Estela Merino-Ramos, T. Saiz Calahorra, Juan Carlos Martín-Acebes, M. A. Infection with Usutu virus induces an autophagic response in mammalian cells |
author_facet |
Blázquez Martín, Ana Belén Escribano Romero, Estela Merino-Ramos, T. Saiz Calahorra, Juan Carlos Martín-Acebes, M. A. |
author_sort |
Blázquez Martín, Ana Belén |
title |
Infection with Usutu virus induces an autophagic response in mammalian cells |
title_short |
Infection with Usutu virus induces an autophagic response in mammalian cells |
title_full |
Infection with Usutu virus induces an autophagic response in mammalian cells |
title_fullStr |
Infection with Usutu virus induces an autophagic response in mammalian cells |
title_full_unstemmed |
Infection with Usutu virus induces an autophagic response in mammalian cells |
title_sort |
infection with usutu virus induces an autophagic response in mammalian cells |
publisher |
Public Library of Science |
publishDate |
2013 |
url |
http://hdl.handle.net/20.500.12792/3940 http://hdl.handle.net/10261/291701 |
work_keys_str_mv |
AT blazquezmartinanabelen infectionwithusutuvirusinducesanautophagicresponseinmammaliancells AT escribanoromeroestela infectionwithusutuvirusinducesanautophagicresponseinmammaliancells AT merinoramost infectionwithusutuvirusinducesanautophagicresponseinmammaliancells AT saizcalahorrajuancarlos infectionwithusutuvirusinducesanautophagicresponseinmammaliancells AT martinacebesma infectionwithusutuvirusinducesanautophagicresponseinmammaliancells |
_version_ |
1767603243170398208 |