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The poxvirus F17 protein counteracts mitochondrially orchestrated antiviral responses.

Authors :
Meade N
Toreev HK
Chakrabarty RP
Hesser CR
Park C
Chandel NS
Walsh D
Source :
Nature communications [Nat Commun] 2023 Nov 30; Vol. 14 (1), pp. 7889. Date of Electronic Publication: 2023 Nov 30.
Publication Year :
2023

Abstract

Poxviruses are unusual DNA viruses that replicate in the cytoplasm. To do so, they encode approximately 100 immunomodulatory proteins that counteract cytosolic nucleic acid sensors such as cGAMP synthase (cGAS) along with several other antiviral response pathways. Yet most of these immunomodulators are expressed very early in infection while many are variable host range determinants, and significant gaps remain in our understanding of poxvirus sensing and evasion strategies. Here, we show that after infection is established, subsequent progression of the viral lifecycle is sensed through specific changes to mitochondria that coordinate distinct aspects of the antiviral response. Unlike other viruses that cause extensive mitochondrial damage, poxviruses sustain key mitochondrial functions including membrane potential and respiration while reducing reactive oxygen species that drive inflammation. However, poxvirus replication induces mitochondrial hyperfusion that independently controls the release of mitochondrial DNA (mtDNA) to prime nucleic acid sensors and enables an increase in glycolysis that is necessary to support interferon stimulated gene (ISG) production. To counter this, the poxvirus F17 protein localizes to mitochondria and dysregulates mTOR to simultaneously destabilize cGAS and block increases in glycolysis. Our findings reveal how the poxvirus F17 protein disarms specific mitochondrially orchestrated responses to later stages of poxvirus replication.<br /> (© 2023. The Author(s).)

Details

Language :
English
ISSN :
2041-1723
Volume :
14
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
38036506
Full Text :
https://doi.org/10.1038/s41467-023-43635-y