Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/6496
Título
ISG15 governs mitochondrial function in macrophages following vaccinia
virus infection
Autor(es)
Baldanta, Sara | Fernandez-Escobar, Mercedes | Acin-Perez, Rebeca CNIC | Albert, Manuel | Camafeita, Emilio CNIC | Jorge, Inmaculada CNIC | Vazquez, Jesus CNIC | Enriquez, Jose Antonio CNIC | Guerra, Susana
Fecha de publicación
2017
Cita
PLoS Pathog. 2017; 13(10):e1006651
Idioma
Inglés
Tipo de documento
journal article
Resumen
The interferon (IFN)-stimulated gene 15 (ISG15) encodes one of the most
abundant proteins induced by interferon, and its expression is
associated with antiviral immunity. To identify protein components
implicated in IFN and ISG15 signaling, we compared the proteomes of
ISG15(-/-) and ISG15(+/+) bone marrow derived macrophages (BMDM) after
vaccinia virus (VACV) infection. The results of this analysis revealed
that mitochondrial dysfunction and oxidative phosphorylation (OXPHOS)
were pathways altered in ISG15(-/-) BMDM treated with IFN. Mitochondrial
respiration, Adenosine triphosphate (ATP) and reactive oxygen species
(ROS) production was higher in ISG15(+/+) BMDM than in ISG15(-/-) BMDM
following IFN treatment, indicating the involvement of ISG15-dependent
mechanisms. An additional consequence of ISG15 depletion was a
significant change in macrophage polarization. Although infected
ISG15(-/-) macrophages showed a robust proinflammatory cytokine
expression pattern typical of an M1 phenotype, a clear blockade of
nitric oxide (NO) production and arginase- 1 activation was detected.
Accordingly, following IFN treatment, NO release was higher in
ISG15(+/+) macrophages than in ISG15(-/-) macrophages concomitant with a
decrease in viral titer. Thus, ISG15(-/-) macrophages were permissive
for VACV replication following IFN treatment. In conclusion, our results
demonstrate that ISG15 governs the dynamic functionality of
mitochondria, specifically, OXPHOS and mitophagy, broadening its
physiological role as an antiviral agent.
Palabras clave
UBIQUITIN-LIKE PROTEIN | INTERFERON-STIMULATED GENE | INNATE ANTIVIRAL
RESPONSE | CONJUGATION SYSTEM | IN-VIVO | QUANTITATIVE PROTEOMICS | PEPTIDE
IDENTIFICATION | VIRAL RESISTANCE | IMMUNE-SYSTEM | HOST-DEFENSE
Versión en línea
DOI
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