TY - JOUR
T1 - eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production
AU - Seoane, Rocío
AU - Llamas-González, Yessica Y.
AU - Vidal, Santiago
AU - El Motiam, Ahmed
AU - Bouzaher, Yanis Hichem
AU - Fonseca, Danae
AU - Farrás, Rosa
AU - García-Sastre, Adolfo
AU - González-Santamaría, José
AU - Rivas, Carmen
N1 - Funding Information:
Funding at the laboratory of CR is provided by Ministry of Science, Innovation and Universities and FEDER (BFU-2017-88880-P), (PID2021-126510NB-I00), and Xunta de Galicia (ED431G 2019/02). RS and SV are predoctoral fellows funded by Xunta de Galicia-Consellería de Cultura, Educación y Ordenación Universitaria (ED481A-2020/160 and ED481A-2018/110, respectively). JG-S was supported by grants from Secretaría Nacional de Ciencia, Tecnología e Innovación de Panamá (SENACYT), grant number FID18-100, Ministerio de Economía y Finanzas, grant number 19911.012 and Sistema Nacional de Investigación (SNI from SENACYT), grant number 23-2021. This work was also partly supported by CRIPT (Center for Research on Influenza Pathogenesis and Transmission), an NIAID funded Center of Excellence for Influenza Research and Response (CEIRR, contract # 75N93021C00014) to AG-S.
Publisher Copyright:
Copyright © 2022 Seoane, Llamas-González, Vidal, El Motiam, Bouzaher, Fonseca, Farrás, García-Sastre, González-Santamaría and Rivas.
PY - 2022/7/27
Y1 - 2022/7/27
N2 - 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.
AB - 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.
KW - GC7
KW - dsRNA
KW - eIF5A1
KW - hypusine
KW - influenza
KW - interferon
KW - virus
UR - http://www.scopus.com/inward/record.url?scp=85135790955&partnerID=8YFLogxK
U2 - 10.3389/fcimb.2022.960138
DO - 10.3389/fcimb.2022.960138
M3 - Article
AN - SCOPUS:85135790955
SN - 2235-2988
VL - 12
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
M1 - 960138
ER -