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...

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Detalles Bibliográficos
Autores: Seoane, Rocío, Llamas-González, Yessica Y., Vidal, Santiago, Motiam, Ahmed El, Bouzaher, Yanis H., Fonseca, Danae, Farràs, Rosa, García-Sastre, Adolfo, González-Santamaría, José, Rivas, Carmen
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/377802
Acceso en línea:http://hdl.handle.net/10261/377802
Access Level:acceso abierto
Palabra clave:EIF5A1
Hypusine
Virus
dsRN
GC7
Influenza
Interferon
Descripción
Sumario: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.