eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production
Active hypusine-modified initiation elongation factor 5A is critical for cell proliferation and differentiation, embryonic development, and innate immune response of macrophages to bacterial infection. Here, we demonstrate that both virus infection and double-stranded RNA viral mimic stimulation ind...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.960138/full |
| _version_ | 1811221685154611200 |
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| author | Rocío Seoane Yessica Y. Llamas-González Yessica Y. Llamas-González Santiago Vidal Ahmed El Motiam Yanis Hichem Bouzaher Danae Fonseca Rosa Farrás Adolfo García-Sastre Adolfo García-Sastre Adolfo García-Sastre Adolfo García-Sastre Adolfo García-Sastre José González-Santamaría Carmen Rivas Carmen Rivas |
| author_facet | Rocío Seoane Yessica Y. Llamas-González Yessica Y. Llamas-González Santiago Vidal Ahmed El Motiam Yanis Hichem Bouzaher Danae Fonseca Rosa Farrás Adolfo García-Sastre Adolfo García-Sastre Adolfo García-Sastre Adolfo García-Sastre Adolfo García-Sastre José González-Santamaría Carmen Rivas Carmen Rivas |
| author_sort | Rocío Seoane |
| collection | DOAJ |
| description | Active hypusine-modified initiation elongation factor 5A is critical for cell proliferation and differentiation, embryonic development, and innate immune response of macrophages to bacterial infection. Here, we demonstrate that both virus infection and double-stranded RNA viral mimic stimulation induce the hypusination of eIF5A. Furthermore, we show that activation of eIF5A is essential for the replication of several RNA viruses including influenza A virus, vesicular stomatitis virus, chikungunya virus, mayaro virus, una virus, zika virus, and punta toro virus. Finally, our data reveal that inhibition of eIF5A hypusination using the spermidine analog GC7 or siRNA-mediated downmodulation of eIF5A1 induce upregulation of endoplasmic reticulum stress marker proteins and trigger the transcriptional induction of interferon and interferon-stimulated genes, mechanisms that may explain the broad-spectrum antiviral activity of eIF5A inhibition. |
| first_indexed | 2024-04-12T08:04:48Z |
| format | Article |
| id | doaj.art-c0550d7e701f4dcfbc32f86de59eebce |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-12T08:04:48Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-c0550d7e701f4dcfbc32f86de59eebce2022-12-22T03:41:12ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-07-011210.3389/fcimb.2022.960138960138eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon productionRocío Seoane0Yessica Y. Llamas-González1Yessica Y. Llamas-González2Santiago Vidal3Ahmed El Motiam4Yanis Hichem Bouzaher5Danae Fonseca6Rosa Farrás7Adolfo García-Sastre8Adolfo García-Sastre9Adolfo García-Sastre10Adolfo García-Sastre11Adolfo García-Sastre12José González-Santamaría13Carmen Rivas14Carmen Rivas15Centro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, SpainGrupo de Biología Celular y Molecular de Arbovirus, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panamá, PanamaPrograma de Doctorado en Ciencias Biológicas, Universidad de la República, Montevideo, UruguayCentro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, SpainCentro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, SpainCentro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, SpainDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesOncogenic Signalling Laboratory, Centro de Investigación Príncipe Felipe, Valencia, SpainDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesGlobal Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesThe Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesGrupo de Biología Celular y Molecular de Arbovirus, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panamá, PanamaCentro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain0Cellular and Molecular Biology, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, SpainActive hypusine-modified initiation elongation factor 5A is critical for cell proliferation and differentiation, embryonic development, and innate immune response of macrophages to bacterial infection. Here, we demonstrate that both virus infection and double-stranded RNA viral mimic stimulation induce the hypusination of eIF5A. Furthermore, we show that activation of eIF5A is essential for the replication of several RNA viruses including influenza A virus, vesicular stomatitis virus, chikungunya virus, mayaro virus, una virus, zika virus, and punta toro virus. Finally, our data reveal that inhibition of eIF5A hypusination using the spermidine analog GC7 or siRNA-mediated downmodulation of eIF5A1 induce upregulation of endoplasmic reticulum stress marker proteins and trigger the transcriptional induction of interferon and interferon-stimulated genes, mechanisms that may explain the broad-spectrum antiviral activity of eIF5A inhibition.https://www.frontiersin.org/articles/10.3389/fcimb.2022.960138/fulleIF5A1hypusinevirusdsRNAGC7influenza |
| spellingShingle | Rocío Seoane Yessica Y. Llamas-González Yessica Y. Llamas-González Santiago Vidal Ahmed El Motiam Yanis Hichem Bouzaher Danae Fonseca Rosa Farrás Adolfo García-Sastre Adolfo García-Sastre Adolfo García-Sastre Adolfo García-Sastre Adolfo García-Sastre José González-Santamaría Carmen Rivas Carmen Rivas eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production Frontiers in Cellular and Infection Microbiology eIF5A1 hypusine virus dsRNA GC7 influenza |
| title | eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production |
| title_full | eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production |
| title_fullStr | eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production |
| title_full_unstemmed | eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production |
| title_short | eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production |
| title_sort | eif5a is activated by virus infection or dsrna and facilitates virus replication through modulation of interferon production |
| topic | eIF5A1 hypusine virus dsRNA GC7 influenza |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.960138/full |
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