Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections
Identifieur interne : 005591 ( Main/Merge ); précédent : 005590; suivant : 005592Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections
Auteurs : Amandine Crequer [États-Unis, France] ; Anja Troeger [États-Unis] ; Etienne Patin [France] ; Cindy S. Ma ; Capucine Picard [France] ; Vincent Pedergnana [France] ; Claire Fieschi [France] ; Annick Lim [France] ; Avinash Abhyankar [États-Unis] ; Laure Gineau [France] ; Ingrid Mueller-Fleckenstein [Allemagne] ; Monika Schmidt [Allemagne] ; Alain Taieb [France] ; James Krueger [États-Unis] ; Laurent Abel [États-Unis, France] ; Stuart G. Tangye ; Gérard Orth [France] ; David A. Williams [États-Unis] ; Jean-Laurent Casanova [États-Unis, France] ; Emmanuelle Jouanguy [États-Unis, France]Source :
- The Journal of Clinical Investigation [ 0021-9738 ] ; 2012.
Abstract
Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by increased susceptibility to specific human papillomaviruses, the betapapillomaviruses. These EV-HPVs cause warts and increase the risk of skin carcinomas in otherwise healthy individuals. Inactivating mutations in epidermodysplasia verruciformis 1 (
Url:
DOI: 10.1172/JCI62949
PubMed: 22850876
PubMed Central: 3428089
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PMC:3428089Le document en format XML
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<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, 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="Troeger, Anja" sort="Troeger, Anja" uniqKey="Troeger A" first="Anja" last="Troeger">Anja Troeger</name>
<affiliation wicri:level="2"><nlm:aff id="JCI62949">Division of Hematology/Oncology, Children’s Hospital Boston and Dana-Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>Division of Hematology/Oncology, Children’s Hospital Boston and Dana-Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Patin, Etienne" sort="Patin, Etienne" uniqKey="Patin E" first="Etienne" last="Patin">Etienne Patin</name>
<affiliation wicri:level="3"><nlm:aff id="JCI62949">Human Evolutionary Genetics, CNRS URA 3012, Genomes and Genetics Department, Pasteur Institute, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Human Evolutionary Genetics, CNRS URA 3012, Genomes and Genetics Department, Pasteur Institute, 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="Ma, Cindy S" sort="Ma, Cindy S" uniqKey="Ma C" first="Cindy S." last="Ma">Cindy S. Ma</name>
<affiliation><nlm:aff id="JCI62949">Immunology Program, Garvan Institute of Medical Research, Sydney, Australia, and St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney Australia.</nlm:aff>
<wicri:noCountry code="subfield">Sydney Australia.</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name>
<affiliation wicri:level="3"><nlm:aff id="JCI62949">Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, 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"><nlm:aff id="JCI62949">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, 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"><nlm:aff id="JCI62949">Study Center for Primary Immunodeficiencies, Necker Hospital, AP-HP, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Study Center for Primary Immunodeficiencies, Necker Hospital, AP-HP, 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="Pedergnana, Vincent" sort="Pedergnana, Vincent" uniqKey="Pedergnana V" first="Vincent" last="Pedergnana">Vincent Pedergnana</name>
<affiliation wicri:level="3"><nlm:aff id="JCI62949">Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, 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"><nlm:aff id="JCI62949">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, 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="Fieschi, Claire" sort="Fieschi, Claire" uniqKey="Fieschi C" first="Claire" last="Fieschi">Claire Fieschi</name>
<affiliation wicri:level="3"><nlm:aff id="JCI62949">Department of Clinical Immunology, Saint-Louis Hospital, Assitance Publique-Hôpitaux de Paris and Paris Diderot University, Sorbonne Paris Cité, EA3963, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Department of Clinical Immunology, Saint-Louis Hospital, Assitance Publique-Hôpitaux de Paris and Paris Diderot University, Sorbonne Paris Cité, EA3963, 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="Lim, Annick" sort="Lim, Annick" uniqKey="Lim A" first="Annick" last="Lim">Annick Lim</name>
<affiliation wicri:level="3"><nlm:aff id="JCI62949">Department of Immunology, Pasteur Institute, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Department of Immunology, Pasteur Institute, 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="Abhyankar, Avinash" sort="Abhyankar, Avinash" uniqKey="Abhyankar A" first="Avinash" last="Abhyankar">Avinash Abhyankar</name>
<affiliation wicri:level="2"><nlm:aff id="JCI62949">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gineau, Laure" sort="Gineau, Laure" uniqKey="Gineau L" first="Laure" last="Gineau">Laure Gineau</name>
<affiliation wicri:level="3"><nlm:aff id="JCI62949">Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, 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"><nlm:aff id="JCI62949">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, 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="Mueller Fleckenstein, Ingrid" sort="Mueller Fleckenstein, Ingrid" uniqKey="Mueller Fleckenstein I" first="Ingrid" last="Mueller-Fleckenstein">Ingrid Mueller-Fleckenstein</name>
<affiliation wicri:level="1"><nlm:aff id="JCI62949">Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nurnberg, Germany.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Allemagne</country>
<wicri:regionArea>Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nurnberg</wicri:regionArea>
<wicri:noRegion>Universität Erlangen-Nurnberg</wicri:noRegion>
<wicri:noRegion>Universität Erlangen-Nurnberg</wicri:noRegion>
<wicri:noRegion>Universität Erlangen-Nurnberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Schmidt, Monika" sort="Schmidt, Monika" uniqKey="Schmidt M" first="Monika" last="Schmidt">Monika Schmidt</name>
<affiliation wicri:level="1"><nlm:aff id="JCI62949">Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nurnberg, Germany.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Allemagne</country>
<wicri:regionArea>Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nurnberg</wicri:regionArea>
<wicri:noRegion>Universität Erlangen-Nurnberg</wicri:noRegion>
<wicri:noRegion>Universität Erlangen-Nurnberg</wicri:noRegion>
<wicri:noRegion>Universität Erlangen-Nurnberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Taieb, Alain" sort="Taieb, Alain" uniqKey="Taieb A" first="Alain" last="Taieb">Alain Taieb</name>
<affiliation wicri:level="4"><nlm:aff id="JCI62949">Pediatric Dermatology Unit, Bordeaux Children’s Hospital, CHU de Bordeaux, and INSERM 1035, Université Bordeaux Segalen, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Pediatric Dermatology Unit, Bordeaux Children’s Hospital, CHU de Bordeaux, and INSERM 1035, Université Bordeaux Segalen</wicri:regionArea>
<wicri:noRegion>Université Bordeaux Segalen</wicri:noRegion>
<placeName><settlement type="city">Bordeaux</settlement>
<region type="region" nuts="2">Nouvelle-Aquitaine</region>
<region type="old region" nuts="2">Aquitaine</region>
</placeName>
<orgName type="university">Université Bordeaux II</orgName>
<orgName type="institution" wicri:auto="newGroup">Université de Bordeaux</orgName>
</affiliation>
</author>
<author><name sortKey="Krueger, James" sort="Krueger, James" uniqKey="Krueger J" first="James" last="Krueger">James Krueger</name>
<affiliation wicri:level="2"><nlm:aff id="JCI62949">Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Abel, Laurent" sort="Abel, Laurent" uniqKey="Abel L" first="Laurent" last="Abel">Laurent Abel</name>
<affiliation wicri:level="2"><nlm:aff id="JCI62949">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI62949">Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, 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"><nlm:aff id="JCI62949">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, 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="Tangye, Stuart G" sort="Tangye, Stuart G" uniqKey="Tangye S" first="Stuart G." last="Tangye">Stuart G. Tangye</name>
<affiliation><nlm:aff id="JCI62949">Immunology Program, Garvan Institute of Medical Research, Sydney, Australia, and St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney Australia.</nlm:aff>
<wicri:noCountry code="subfield">Sydney Australia.</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Orth, Gerard" sort="Orth, Gerard" uniqKey="Orth G" first="Gérard" last="Orth">Gérard Orth</name>
<affiliation wicri:level="3"><nlm:aff id="JCI62949">Department of Virology, Pasteur Institute, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Department of Virology, Pasteur Institute, 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="Williams, David A" sort="Williams, David A" uniqKey="Williams D" first="David A." last="Williams">David A. Williams</name>
<affiliation wicri:level="2"><nlm:aff id="JCI62949">Division of Hematology/Oncology, Children’s Hospital Boston and Dana-Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>Division of Hematology/Oncology, Children’s Hospital Boston and Dana-Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<affiliation wicri:level="2"><nlm:aff id="JCI62949">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI62949">Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, 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"><nlm:aff id="JCI62949">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, 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"><nlm:aff id="JCI62949">Pediatric Immunohematology Unit, Necker Hospital, AP-HP, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Pediatric Immunohematology Unit, Necker Hospital, AP-HP, 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="Jouanguy, Emmanuelle" sort="Jouanguy, Emmanuelle" uniqKey="Jouanguy E" first="Emmanuelle" last="Jouanguy">Emmanuelle Jouanguy</name>
<affiliation wicri:level="2"><nlm:aff id="JCI62949">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI62949">Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Necker Medicine Faculty, 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"><nlm:aff id="JCI62949">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Paris, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, 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>
</analytic>
<series><title level="j">The Journal of Clinical Investigation</title>
<idno type="ISSN">0021-9738</idno>
<idno type="eISSN">1558-8238</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by increased susceptibility to specific human papillomaviruses, the betapapillomaviruses. These EV-HPVs cause warts and increase the risk of skin carcinomas in otherwise healthy individuals. Inactivating mutations in epidermodysplasia verruciformis 1 (<italic>EVER1</italic>
) or <italic>EVER2</italic>
have been identified in most, but not all, patients with autosomal recessive EV. We found that 2 young adult siblings presenting with T cell deficiency and various infectious diseases, including persistent EV-HPV infections, were homozygous for a mutation creating a stop codon in the ras homolog gene family member H (<italic>RHOH</italic>
) gene. <italic>RHOH</italic>
encodes an atypical Rho GTPase expressed predominantly in hematopoietic cells. Patients’ circulating T cells contained predominantly effector memory T cells, which displayed impaired TCR signaling. Additionally, very few circulating T cells expressed the β<sub>7</sub>
integrin subunit, which homes T cells to specific tissues. Similarly, <italic>Rhoh</italic>
-null mice exhibited a severe overall T cell defect and abnormally small numbers of circulating β<sub>7</sub>
-positive cells. Expression of the WT, but not of the mutated <italic>RHOH</italic>
, allele in <italic>Rhoh<sup>–/–</sup>
</italic>
hematopoietic stem cells corrected the T cell lymphopenia in mice after bone marrow transplantation. We conclude that RHOH deficiency leads to T cell defects and persistent EV-HPV infections, suggesting that T cells play a role in the pathogenesis of chronic EV-HPV infections.
</p>
</div>
</front>
</TEI>
</record>
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