2026-07-21T16:28:25Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/64962024-09-27T08:38:56Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Baldanta, Sara
author
Fernandez-Escobar, Mercedes
author
Acin-Perez, Rebeca
author
Albert, Manuel
author
Camafeita, Emilio
author
Jorge, Inmaculada
author
Vazquez, Jesus
author
Enriquez, Jose Antonio
author
Guerra, Susana
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
2018-10-19T08:00:43Z
2018-10-19T08:00:43Z
2017
PLoS Pathog. 2017; 13(10):e1006651
10.1371/journal.ppat.1006651
1553-7374
1553-7366
PLOS PATHOGENS
29077752
http://hdl.handle.net/20.500.12105/6496
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.
eng
UBIQUITIN-LIKE PROTEIN
INTERFERON-STIMULATED GENE
INNATE ANTIVIRAL
RESPONSE
CONJUGATION SYSTEM
IN-VIVO
QUANTITATIVE PROTEOMICS
PEPTIDE
IDENTIFICATION
VIRAL RESISTANCE
IMMUNE-SYSTEM
HOST-DEFENSE
ISG15 governs mitochondrial function in macrophages following vaccinia
virus infection
journal article
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ISG15GovernsMitochondrialFunction_2017.pdf
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ISG15GovernsMitochondrialFunction_2017.pdf.txt