Natural mutations in IFITM3 modulate post‐translational regulation and toggle antiviral specificity
Identifieur interne : 000117 ( France/Analysis ); précédent : 000116; suivant : 000118Natural mutations in IFITM3 modulate post‐translational regulation and toggle antiviral specificity
Auteurs : Alex A. Compton [France] ; Nicolas Roy [France] ; Françoise Porrot [France] ; Anne Billet [France] ; Nicoletta Casartelli [France] ; Jacob S. Yount [États-Unis] ; Chen Liang [Canada] ; Olivier Schwartz [France]Source :
- EMBO reports [ 1469-221X ] ; 2016-11.
Abstract
The interferon‐induced transmembrane (IFITM) proteins protect host cells from diverse virus infections. IFITM proteins also incorporate into HIV‐1 virions and inhibit virus fusion and cell‐to‐cell spread, with IFITM3 showing the greatest potency. Here, we report that amino‐terminal mutants of IFITM3 preventing ubiquitination and endocytosis are more abundantly incorporated into virions and exhibit enhanced inhibition of HIV‐1 fusion. An analysis of primate genomes revealed that IFITM3 is the most ancient antiviral family member of the IFITM locus and has undergone a repeated duplication in independent host lineages. Some IFITM3 genes in nonhuman primates, including those that arose following gene duplication, carry amino‐terminal mutations that modify protein localization and function. This suggests that “runaway” IFITM3 variants could be selected for altered antiviral activity. Furthermore, we show that adaptations in IFITM3 result in a trade‐off in antiviral specificity, as variants exhibiting enhanced activity against HIV‐1 poorly restrict influenza A virus. Overall, we provide the first experimental evidence that diversification of IFITM3 genes may boost the antiviral coverage of host cells and provide selective functional advantages.
By analyzing synthetic and naturally occurring mutations of interferon‐induced transmembrane 3 (IFITM3), this study provides novel insight into the antiviral mechanisms at play during HIV‐1 infection. The authors further show that the diversification of IFITM3 genes during evolution may boost the antiviral coverage of host cells and provides selective functional advantages. Amino‐terminal mutations of IFITM3 result in an enhanced incorporation into HIV‐1 virions and promote the inhibition of virus–cell fusion. Two adjacent regulatory motifs that control ubiquitination and endocytosis of IFITM3 regulate its potency and antiviral specificity. IFITM3 shows recurrent gene duplication and divergence during primate evolution.
By analyzing synthetic and naturally occurring mutations of interferon‐induced transmembrane 3 (IFITM3), this study provides novel insight into the antiviral mechanisms at play during HIV‐1 infection. The authors further show that the diversification of IFITM3 genes during evolution may boost the antiviral coverage of host cells and provides selective functional advantages.
Url:
DOI: 10.15252/embr.201642771
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 001B37
- to stream Istex, to step Curation: 001B37
- to stream Istex, to step Checkpoint: 000034
- to stream Main, to step Merge: 001130
- to stream Main, to step Curation: 001128
- to stream Main, to step Exploration: 001128
- to stream France, to step Extraction: 000117
Links to Exploration step
ISTEX:E946A461488F96E67F2B7CF5AAB71A9D6422C003Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Natural mutations in IFITM3 modulate post‐translational regulation and toggle antiviral specificity</title><author><name sortKey="Compton, Alex A" sort="Compton, Alex A" uniqKey="Compton A" first="Alex A" last="Compton">Alex A. Compton</name></author><author><name sortKey="Roy, Nicolas" sort="Roy, Nicolas" uniqKey="Roy N" first="Nicolas" last="Roy">Nicolas Roy</name></author><author><name sortKey="Porrot, Francoise" sort="Porrot, Francoise" uniqKey="Porrot F" first="Françoise" last="Porrot">Françoise Porrot</name></author><author><name sortKey="Billet, Anne" sort="Billet, Anne" uniqKey="Billet A" first="Anne" last="Billet">Anne Billet</name></author><author><name sortKey="Casartelli, Nicoletta" sort="Casartelli, Nicoletta" uniqKey="Casartelli N" first="Nicoletta" last="Casartelli">Nicoletta Casartelli</name></author><author><name sortKey="Yount, Jacob S" sort="Yount, Jacob S" uniqKey="Yount J" first="Jacob S" last="Yount">Jacob S. Yount</name></author><author><name sortKey="Liang, Chen" sort="Liang, Chen" uniqKey="Liang C" first="Chen" last="Liang">Chen Liang</name></author><author><name sortKey="Schwartz, Olivier" sort="Schwartz, Olivier" uniqKey="Schwartz O" first="Olivier" last="Schwartz">Olivier Schwartz</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:E946A461488F96E67F2B7CF5AAB71A9D6422C003</idno><date when="2016" year="2016">2016</date><idno type="doi">10.15252/embr.201642771</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-MQ3ZJFWX-P/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001B37</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001B37</idno><idno type="wicri:Area/Istex/Curation">001B37</idno><idno type="wicri:Area/Istex/Checkpoint">000034</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000034</idno><idno type="wicri:doubleKey">1469-221X:2016:Compton A:natural:mutations:in</idno><idno type="wicri:Area/Main/Merge">001130</idno><idno type="wicri:Area/Main/Curation">001128</idno><idno type="wicri:Area/Main/Exploration">001128</idno><idno type="wicri:Area/France/Extraction">000117</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Natural mutations in IFITM3 modulate post‐translational regulation and toggle antiviral specificity</title><author><name sortKey="Compton, Alex A" sort="Compton, Alex A" uniqKey="Compton A" first="Alex A" last="Compton">Alex A. Compton</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Virus & Immunity Unit, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation></author><author><name sortKey="Roy, Nicolas" sort="Roy, Nicolas" uniqKey="Roy N" first="Nicolas" last="Roy">Nicolas Roy</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Virus & Immunity Unit, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Porrot, Francoise" sort="Porrot, Francoise" uniqKey="Porrot F" first="Françoise" last="Porrot">Françoise Porrot</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Virus & Immunity Unit, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Billet, Anne" sort="Billet, Anne" uniqKey="Billet A" first="Anne" last="Billet">Anne Billet</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Virus & Immunity Unit, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Casartelli, Nicoletta" sort="Casartelli, Nicoletta" uniqKey="Casartelli N" first="Nicoletta" last="Casartelli">Nicoletta Casartelli</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Virus & Immunity Unit, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Yount, Jacob S" sort="Yount, Jacob S" uniqKey="Yount J" first="Jacob S" last="Yount">Jacob S. Yount</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbial Infection & Immunity, The Ohio State University, OH, Columbus</wicri:regionArea><wicri:noRegion>Columbus</wicri:noRegion></affiliation></author><author><name sortKey="Liang, Chen" sort="Liang, Chen" uniqKey="Liang C" first="Chen" last="Liang">Chen Liang</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Lady Davis Institute, McGill University, QC, Montreal</wicri:regionArea><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation></author><author><name sortKey="Schwartz, Olivier" sort="Schwartz, Olivier" uniqKey="Schwartz O" first="Olivier" last="Schwartz">Olivier Schwartz</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Virus & Immunity Unit, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>CNRS‐URA 3015, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Vaccine Research Institute, Creteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">EMBO reports</title><title level="j" type="alt">EMBO REPORTS</title><idno type="ISSN">1469-221X</idno><idno type="eISSN">1469-3178</idno><imprint><biblScope unit="vol">17</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1657">1657</biblScope><biblScope unit="page" to="1671">1671</biblScope><biblScope unit="page-count">15</biblScope><date type="published" when="2016-11">2016-11</date></imprint><idno type="ISSN">1469-221X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1469-221X</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">The interferon‐induced transmembrane (IFITM) proteins protect host cells from diverse virus infections. IFITM proteins also incorporate into HIV‐1 virions and inhibit virus fusion and cell‐to‐cell spread, with IFITM3 showing the greatest potency. Here, we report that amino‐terminal mutants of IFITM3 preventing ubiquitination and endocytosis are more abundantly incorporated into virions and exhibit enhanced inhibition of HIV‐1 fusion. An analysis of primate genomes revealed that IFITM3 is the most ancient antiviral family member of the IFITM locus and has undergone a repeated duplication in independent host lineages. Some IFITM3 genes in nonhuman primates, including those that arose following gene duplication, carry amino‐terminal mutations that modify protein localization and function. This suggests that “runaway” IFITM3 variants could be selected for altered antiviral activity. Furthermore, we show that adaptations in IFITM3 result in a trade‐off in antiviral specificity, as variants exhibiting enhanced activity against HIV‐1 poorly restrict influenza A virus. Overall, we provide the first experimental evidence that diversification of IFITM3 genes may boost the antiviral coverage of host cells and provide selective functional advantages.</div><div type="abstract">By analyzing synthetic and naturally occurring mutations of interferon‐induced transmembrane 3 (IFITM3), this study provides novel insight into the antiviral mechanisms at play during HIV‐1 infection. The authors further show that the diversification of IFITM3 genes during evolution may boost the antiviral coverage of host cells and provides selective functional advantages. Amino‐terminal mutations of IFITM3 result in an enhanced incorporation into HIV‐1 virions and promote the inhibition of virus–cell fusion. Two adjacent regulatory motifs that control ubiquitination and endocytosis of IFITM3 regulate its potency and antiviral specificity. IFITM3 shows recurrent gene duplication and divergence during primate evolution.</div><div type="abstract">By analyzing synthetic and naturally occurring mutations of interferon‐induced transmembrane 3 (IFITM3), this study provides novel insight into the antiviral mechanisms at play during HIV‐1 infection. The authors further show that the diversification of IFITM3 genes during evolution may boost the antiviral coverage of host cells and provides selective functional advantages.</div></front></TEI><affiliations><list><country><li>Canada</li><li>France</li><li>États-Unis</li></country><region><li>Québec</li><li>Île-de-France</li></region><settlement><li>Créteil</li><li>Montréal</li><li>Paris</li></settlement><orgName><li>Université McGill</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Compton, Alex A" sort="Compton, Alex A" uniqKey="Compton A" first="Alex A" last="Compton">Alex A. Compton</name></region><name sortKey="Billet, Anne" sort="Billet, Anne" uniqKey="Billet A" first="Anne" last="Billet">Anne Billet</name><name sortKey="Casartelli, Nicoletta" sort="Casartelli, Nicoletta" uniqKey="Casartelli N" first="Nicoletta" last="Casartelli">Nicoletta Casartelli</name><name sortKey="Compton, Alex A" sort="Compton, Alex A" uniqKey="Compton A" first="Alex A" last="Compton">Alex A. Compton</name><name sortKey="Compton, Alex A" sort="Compton, Alex A" uniqKey="Compton A" first="Alex A" last="Compton">Alex A. Compton</name><name sortKey="Compton, Alex A" sort="Compton, Alex A" uniqKey="Compton A" first="Alex A" last="Compton">Alex A. Compton</name><name sortKey="Porrot, Francoise" sort="Porrot, Francoise" uniqKey="Porrot F" first="Françoise" last="Porrot">Françoise Porrot</name><name sortKey="Roy, Nicolas" sort="Roy, Nicolas" uniqKey="Roy N" first="Nicolas" last="Roy">Nicolas Roy</name><name sortKey="Schwartz, Olivier" sort="Schwartz, Olivier" uniqKey="Schwartz O" first="Olivier" last="Schwartz">Olivier Schwartz</name><name sortKey="Schwartz, Olivier" sort="Schwartz, Olivier" uniqKey="Schwartz O" first="Olivier" last="Schwartz">Olivier Schwartz</name><name sortKey="Schwartz, Olivier" sort="Schwartz, Olivier" uniqKey="Schwartz O" first="Olivier" last="Schwartz">Olivier Schwartz</name><name sortKey="Schwartz, Olivier" sort="Schwartz, Olivier" uniqKey="Schwartz O" first="Olivier" last="Schwartz">Olivier Schwartz</name><name sortKey="Schwartz, Olivier" sort="Schwartz, Olivier" uniqKey="Schwartz O" first="Olivier" last="Schwartz">Olivier Schwartz</name><name sortKey="Schwartz, Olivier" sort="Schwartz, Olivier" uniqKey="Schwartz O" first="Olivier" last="Schwartz">Olivier Schwartz</name></country><country name="États-Unis"><noRegion><name sortKey="Yount, Jacob S" sort="Yount, Jacob S" uniqKey="Yount J" first="Jacob S" last="Yount">Jacob S. Yount</name></noRegion></country><country name="Canada"><region name="Québec"><name sortKey="Liang, Chen" sort="Liang, Chen" uniqKey="Liang C" first="Chen" last="Liang">Chen Liang</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/France/Analysis
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000117 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/France/Analysis/biblio.hfd -nk 000117 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= France
|étape= Analysis
|type= RBID
|clé= ISTEX:E946A461488F96E67F2B7CF5AAB71A9D6422C003
|texte= Natural mutations in IFITM3 modulate post‐translational regulation and toggle antiviral specificity
}}
| This area was generated with Dilib version V0.6.33. |  |