eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production
Por:
R. SEOANE, Y. LLAMAS-GONZALEZ, S. VIDAL, A. EL MOTIAM, Y. BOUZAHER, D. FONSECA, R. FARRAS, A. GARCIA-SASTRE, J. GONZALEZ-SANTAMARIA and C. RIVAS
Publicada:
27 jul 2022
Resumen:
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.
Filiaciones:
R. SEOANE:
Univ Santiago Compostela, Ctr Invest Med Mol & Enfermedades Cron CIMUS, Inst Invest Sanitarias IDIS, Santiago De Compostela, Spain
Y. LLAMAS-GONZALEZ:
Inst Conmemorat Gorgas Estudios Salud, Grp Biol Celular & Mol Arbovirus, Panama City, Panama
Univ Republica, Programa Doctorado Ciencias Biol, Montevideo, Uruguay
S. VIDAL:
Univ Santiago Compostela, Ctr Invest Med Mol & Enfermedades Cron CIMUS, Inst Invest Sanitarias IDIS, Santiago De Compostela, Spain
A. EL MOTIAM:
Univ Santiago Compostela, Ctr Invest Med Mol & Enfermedades Cron CIMUS, Inst Invest Sanitarias IDIS, Santiago De Compostela, Spain
Y. BOUZAHER:
Univ Santiago Compostela, Ctr Invest Med Mol & Enfermedades Cron CIMUS, Inst Invest Sanitarias IDIS, Santiago De Compostela, Spain
D. FONSECA:
Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY USA
:
Ctr Invest Principe Felipe, Oncogen Signalling Lab, Valencia, Spain
A. GARCIA-SASTRE:
Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY USA
Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY USA
Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY USA
Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY USA
Icahn Sch Med Mt Sinai, Dept Pathol Mol & Cell Based Med, New York, NY USA
J. GONZALEZ-SANTAMARIA:
Inst Conmemorat Gorgas Estudios Salud, Grp Biol Celular & Mol Arbovirus, Panama City, Panama
C. RIVAS:
Univ Santiago Compostela, Ctr Invest Med Mol & Enfermedades Cron CIMUS, Inst Invest Sanitarias IDIS, Santiago De Compostela, Spain
Ctr Nacl Biotecnol CNB CSIC, Cellular & Mol Biol, Madrid, Spain
gold, Green Published
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