An influenza virus-triggered SUMO switch orchestrates co-opted endogenous retroviruses to stimulate host antiviral immunity.
Identifieur interne : 000916 ( Main/Exploration ); précédent : 000915; suivant : 000917An influenza virus-triggered SUMO switch orchestrates co-opted endogenous retroviruses to stimulate host antiviral immunity.
Auteurs : Nora Schmidt [Suisse] ; Patricia Domingues [Suisse] ; Filip Golebiowski [Suisse] ; Corinna Patzina [Suisse] ; Michael H. Tatham [Royaume-Uni] ; Ronald T. Hay [Royaume-Uni] ; Benjamin G. Hale [Suisse]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2019.
Descripteurs français
- KwdFr :
- ARN double brin (métabolisme), Animaux, Grippe humaine (métabolisme), Grippe humaine (virologie), Humains, Immunité innée (immunologie), Interactions hôte-pathogène (immunologie), Interactions microbiennes, Modèles biologiques, Protéine SUMO-1 (métabolisme), Réplication virale, Rétrovirus endogènes (immunologie), Sumoylation, Virus de la grippe A (physiologie).
- MESH :
- immunologie : Immunité innée, Interactions hôte-pathogène, Rétrovirus endogènes.
- métabolisme : ARN double brin, Grippe humaine, Protéine SUMO-1.
- physiologie : Virus de la grippe A.
- virologie : Grippe humaine.
- Animaux, Humains, Interactions microbiennes, Modèles biologiques, Réplication virale, Sumoylation.
English descriptors
- KwdEn :
- Animals, Endogenous Retroviruses (immunology), Host-Pathogen Interactions (immunology), Humans, Immunity, Innate (immunology), Influenza A virus (physiology), Influenza, Human (metabolism), Influenza, Human (virology), Microbial Interactions, Models, Biological, RNA, Double-Stranded (metabolism), SUMO-1 Protein (metabolism), Sumoylation, Tripartite Motif-Containing Protein 28 (metabolism), Virus Replication.
- MESH :
- chemical , metabolism : RNA, Double-Stranded, SUMO-1 Protein, Tripartite Motif-Containing Protein 28.
- immunology : Endogenous Retroviruses, Host-Pathogen Interactions, Immunity, Innate.
- metabolism : Influenza, Human.
- physiology : Influenza A virus.
- virology : Influenza, Human.
- Animals, Humans, Microbial Interactions, Models, Biological, Sumoylation, Virus Replication.
Abstract
Dynamic small ubiquitin-like modifier (SUMO) linkages to diverse cellular protein groups are critical to orchestrate resolution of stresses such as genome damage, hypoxia, or proteotoxicity. Defense against pathogen insult (often reliant upon host recognition of "non-self" nucleic acids) is also modulated by SUMO, but the underlying mechanisms are incompletely understood. Here, we used quantitative SILAC-based proteomics to survey pan-viral host SUMOylation responses, creating a resource of almost 600 common and unique SUMO remodeling events that are mounted during influenza A and B virus infections, as well as during viral innate immune stimulation. Subsequent mechanistic profiling focused on a common infection-induced loss of the SUMO-modified form of TRIM28/KAP1, a host transcriptional repressor. By integrating knockout and reconstitution models with system-wide transcriptomics, we provide evidence that influenza virus-triggered loss of SUMO-modified TRIM28 leads to derepression of endogenous retroviral (ERV) elements, unmasking this cellular source of "self" double-stranded (ds)RNA. Consequently, loss of SUMO-modified TRIM28 potentiates canonical cytosolic dsRNA-activated IFN-mediated defenses that rely on RIG-I, MAVS, TBK1, and JAK1. Intriguingly, although wild-type influenza A virus robustly triggers this SUMO switch in TRIM28, the induction of IFN-stimulated genes is limited unless expression of the viral dsRNA-binding protein NS1 is abrogated. This may imply a viral strategy to antagonize such a host response by sequestration of induced immunostimulatory ERV dsRNAs. Overall, our data reveal that a key nuclear mechanism that normally prevents aberrant expression of ERV elements (ERVs) has been functionally co-opted via a stress-induced SUMO switch to augment antiviral immunity.
DOI: 10.1073/pnas.1907031116
PubMed: 31391303
Affiliations:
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Le document en format XML
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Hay</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, DD1 5EH Dundee, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, DD1 5EH Dundee</wicri:regionArea><wicri:noRegion>DD1 5EH Dundee</wicri:noRegion></affiliation></author><author><name sortKey="Hale, Benjamin G" sort="Hale, Benjamin G" uniqKey="Hale B" first="Benjamin G" last="Hale">Benjamin G. Hale</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Medical Virology, University of Zurich, 8057 Zurich, Switzerland; hale.ben@virology.uzh.ch.</nlm:affiliation><country wicri:rule="url">Suisse</country><wicri:regionArea>Institute of Medical Virology, University of Zurich, 8057 Zurich</wicri:regionArea><orgName type="university">Université de Zurich</orgName><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Endogenous Retroviruses (immunology)</term><term>Host-Pathogen Interactions (immunology)</term><term>Humans</term><term>Immunity, Innate (immunology)</term><term>Influenza A virus (physiology)</term><term>Influenza, Human (metabolism)</term><term>Influenza, Human (virology)</term><term>Microbial Interactions</term><term>Models, Biological</term><term>RNA, Double-Stranded (metabolism)</term><term>SUMO-1 Protein (metabolism)</term><term>Sumoylation</term><term>Tripartite Motif-Containing Protein 28 (metabolism)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN double brin (métabolisme)</term><term>Animaux</term><term>Grippe humaine (métabolisme)</term><term>Grippe humaine (virologie)</term><term>Humains</term><term>Immunité innée (immunologie)</term><term>Interactions hôte-pathogène (immunologie)</term><term>Interactions microbiennes</term><term>Modèles biologiques</term><term>Protéine SUMO-1 (métabolisme)</term><term>Réplication virale</term><term>Rétrovirus endogènes (immunologie)</term><term>Sumoylation</term><term>Virus de la grippe A (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA, Double-Stranded</term><term>SUMO-1 Protein</term><term>Tripartite Motif-Containing Protein 28</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Immunité innée</term><term>Interactions hôte-pathogène</term><term>Rétrovirus endogènes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Endogenous Retroviruses</term><term>Host-Pathogen Interactions</term><term>Immunity, Innate</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN double brin</term><term>Grippe humaine</term><term>Protéine SUMO-1</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Grippe humaine</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Microbial Interactions</term><term>Models, Biological</term><term>Sumoylation</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Interactions microbiennes</term><term>Modèles biologiques</term><term>Réplication virale</term><term>Sumoylation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Dynamic small ubiquitin-like modifier (SUMO) linkages to diverse cellular protein groups are critical to orchestrate resolution of stresses such as genome damage, hypoxia, or proteotoxicity. Defense against pathogen insult (often reliant upon host recognition of "non-self" nucleic acids) is also modulated by SUMO, but the underlying mechanisms are incompletely understood. Here, we used quantitative SILAC-based proteomics to survey pan-viral host SUMOylation responses, creating a resource of almost 600 common and unique SUMO remodeling events that are mounted during influenza A and B virus infections, as well as during viral innate immune stimulation. Subsequent mechanistic profiling focused on a common infection-induced loss of the SUMO-modified form of TRIM28/KAP1, a host transcriptional repressor. By integrating knockout and reconstitution models with system-wide transcriptomics, we provide evidence that influenza virus-triggered loss of SUMO-modified TRIM28 leads to derepression of endogenous retroviral (ERV) elements, unmasking this cellular source of "self" double-stranded (ds)RNA. Consequently, loss of SUMO-modified TRIM28 potentiates canonical cytosolic dsRNA-activated IFN-mediated defenses that rely on RIG-I, MAVS, TBK1, and JAK1. Intriguingly, although wild-type influenza A virus robustly triggers this SUMO switch in TRIM28, the induction of IFN-stimulated genes is limited unless expression of the viral dsRNA-binding protein NS1 is abrogated. This may imply a viral strategy to antagonize such a host response by sequestration of induced immunostimulatory ERV dsRNAs. Overall, our data reveal that a key nuclear mechanism that normally prevents aberrant expression of ERV elements (ERVs) has been functionally co-opted via a stress-induced SUMO switch to augment antiviral immunity.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li><li>Suisse</li></country><region><li>Canton de Zurich</li></region><settlement><li>Zurich</li></settlement><orgName><li>Université de Zurich</li></orgName></list><tree><country name="Suisse"><region name="Canton de Zurich"><name sortKey="Schmidt, Nora" sort="Schmidt, Nora" uniqKey="Schmidt N" first="Nora" last="Schmidt">Nora Schmidt</name></region><name sortKey="Domingues, Patricia" sort="Domingues, Patricia" uniqKey="Domingues P" first="Patricia" last="Domingues">Patricia Domingues</name><name sortKey="Golebiowski, Filip" sort="Golebiowski, Filip" uniqKey="Golebiowski F" first="Filip" last="Golebiowski">Filip Golebiowski</name><name sortKey="Hale, Benjamin G" sort="Hale, Benjamin G" uniqKey="Hale B" first="Benjamin G" last="Hale">Benjamin G. Hale</name><name sortKey="Patzina, Corinna" sort="Patzina, Corinna" uniqKey="Patzina C" first="Corinna" last="Patzina">Corinna Patzina</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Tatham, Michael H" sort="Tatham, Michael H" uniqKey="Tatham M" first="Michael H" last="Tatham">Michael H. Tatham</name></noRegion><name sortKey="Hay, Ronald T" sort="Hay, Ronald T" uniqKey="Hay R" first="Ronald T" last="Hay">Ronald T. Hay</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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