In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 2 ( 2021-2-17), p. e1009340-
Abstract:
Influenza virus infections are major public health threats due to their high rates of morbidity and mortality. Upon influenza virus entry, host cells experience modifications of endomembranes, including those used for virus trafficking and replication. Here we report that influenza virus infection modifies mitochondrial morphodynamics by promoting mitochondria elongation and altering endoplasmic reticulum-mitochondria tethering in host cells. Expression of the viral RNA recapitulates these modifications inside cells. Virus induced mitochondria hyper-elongation was promoted by fission associated protein DRP1 relocalization to the cytosol, enhancing a pro-fusion status. We show that altering mitochondrial hyper-fusion with Mito-C, a novel pro-fission compound, not only restores mitochondrial morphodynamics and endoplasmic reticulum-mitochondria contact sites but also dramatically reduces influenza replication. Finally, we demonstrate that the observed Mito-C antiviral property is directly connected with the innate immunity signaling RIG-I complex at mitochondria. Our data highlight the importance of a functional interchange between mitochondrial morphodynamics and innate immunity machineries in the context of influenza viral infection.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009340
DOI:
10.1371/journal.ppat.1009340.g001
DOI:
10.1371/journal.ppat.1009340.g002
DOI:
10.1371/journal.ppat.1009340.g003
DOI:
10.1371/journal.ppat.1009340.g004
DOI:
10.1371/journal.ppat.1009340.g005
DOI:
10.1371/journal.ppat.1009340.s001
DOI:
10.1371/journal.ppat.1009340.s002
DOI:
10.1371/journal.ppat.1009340.s003
DOI:
10.1371/journal.ppat.1009340.s004
DOI:
10.1371/journal.ppat.1009340.s005
DOI:
10.1371/journal.ppat.1009340.s006
DOI:
10.1371/journal.ppat.1009340.s007
DOI:
10.1371/journal.ppat.1009340.s008
DOI:
10.1371/journal.ppat.1009340.s009
DOI:
10.1371/journal.ppat.1009340.s010
DOI:
10.1371/journal.ppat.1009340.r001
DOI:
10.1371/journal.ppat.1009340.r002
DOI:
10.1371/journal.ppat.1009340.r003
DOI:
10.1371/journal.ppat.1009340.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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